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Lewis Rats (lewi + rat)
Kinds of Lewis Rats Selected AbstractsWhole-Genome Scan for Linkage to Bone Strength and Structure in Inbred Fischer 344 and Lewis Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Imranul Alam Abstract A genome-wide genetic linkage analysis identified several chromosomal regions influencing bone strength and structure in F2 progeny of Fischer 344 x Lewis inbred rats. Introduction: Inbred Fischer 344 (F344) and Lewis (LEW) rats are similar in body size, but the F344 rats have significantly lower BMD and biomechanical strength of the femur and spine compared with LEW rats. The goal of this study was to identify quantitative trait loci (QTL) linked to bone strength and structure in adult female F2 rats from F344 and LEW progenitors. Materials and Methods: The 595 F2 progeny from F344 x LEW rats were phenotyped for measures of bone strength (ultimate force {Fu}; energy to break {U}; stiffness {S}) of the femur and lumbar vertebra and structure (femur midshaft polar moment of inertia {Ip}; femur midshaft cortical area; vertebral area). A genome-wide scan was completed in the F2 rats using 118 microsatellite markers at an average interval of 20 cM. Multipoint quantitative linkage analysis was performed to identify chromosomal regions that harbor QTL for bone strength and structure phenotypes. Results: Evidence of linkage for femur and lumbar strength was observed on chromosomes (Chrs) 1, 2, 5, 10, and 19. Significant linkage for femoral structure was detected on Chrs 2, 4, 5, 7, and 15. QTLs affecting femoral strength on Chrs 2 and 5 were also found to influence femur structure. Unique QTLs on Chrs 1, 10, and 19 were found that contributed to variability in bone strength but had no significant effect on structure. Also, unique QTLs were observed on Chrs 4, 7, and 15 that affected only bone structure without any effect on biomechanics. Conclusion: We showed multiple genetic loci influencing bone strength and structure in F344 x LEW F2 rats. Some of these loci are homologous to mouse and human chromosomes previously linked to related bone phenotypes. [source] Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningocerebellitis in the Lewis rat: A model for cell-mediated autoimmune neuropathology,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2002Margit G. Proescholdt Abstract Neuronal elements are increasingly suggested as primary targets of an autoimmune attack in certain neurological and neuropsychiatric diseases. Type 1 cannabinoid receptors (CB1) were selected as autoimmune targets because they are predominantly expressed on neuronal surfaces in brain and display strikingly high protein levels in striatum, hippocampus, and cerebellum. Female Lewis rats were immunized with N-terminally acetylated peptides (50 or 400 ,g per rat) of the extracellular domains of the rat CB1 and killed at various time points. Subsequent evaluation using immunohistochemistry and in situ hybridization showed dense infiltration of immune cells exclusively within the cerebellum, peaking 12,16 days after immunization with the CB1 peptide containing amino acids 9,25. The infiltrates clustered in meninges and perivascular locations in molecular and granular cell layers and were also scattered throughout the CB1-rich neuropil. They consisted primarily of CD4+ and ED1+ cells, suggestive of cell-mediated autoimmune pathology. There were no inflammatory infiltrates elsewhere in the brain or spinal cord. The results show that neuronal elements, such as neuronal cell-surface receptors, may be recognized as antigenic targets in a cell-mediated autoimmune attack and, therefore, support the hypothesis of cell-mediated antineuronal autoimmune pathology in certain brain disorders. Published 2002 Wiley-Liss, Inc. [source] Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003James Abstract Viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. In the present study, two different rodent models of experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the ability of murine gammaherpesvirus-68 (,HV-68) to exacerbate development of neurological symptoms. SJL mice received UV-inactivated ,HV-68 or intranasal,HV-68, followed by immunization against proteolipid-protein peptide 139,151. Infected mice became moribund within 10,days post-immunization, whereas mice exposed to UV-inactivated ,HV-68 recovered. In the second model, Lewis rats were exposed to UV-inactivated ,HV-68 or to ,HV-68, followed by passive transfer of encephalitogenic T lymphocytes specific for myelin basic protein. Consistently, infected rats had higher clinical scores, and this result was observed during acute or latent ,HV-68 infection. It is unlikely that this ,HV-68-induced exacerbation was due to significant viral replication within the central nervous system since nested PCR, viral plaque assays, and infectious-centers assays demonstrated no detectable virus in spinal cords or brains of infected rodents undergoing EAE. Taken together, these studies demonstrate increased clinical symptoms of EAE in rodents infected by a gammaherpesvirus that has a limited ability to invade the central nervous system. [source] Lymphotoxin,, receptor-Ig fusion protein treatment blocks actively induced, but not adoptively transferred, uveitis in Lewis ratsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Hui Shao Abstract Previous studies have shown that treatment of rodents with a lymphotoxin (LT),, receptor-Ig fusion protein (LT,R-Ig), which binds to both LT and LIGHT, prevents the development of autoimmune diseases, but the mechanism involved is unclear. To explore the potential role of LT or LIGHT in the pathogenesis of autoimmune uveitis, uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of R16-specific T,cells. Interestingly, LT,R-Ig treatment completely prevented actively induced uveitis, but not the adoptively transferred disease. We also show that LT,R-Ig-treated R16-injected rats had a significantly decreased T,cell response to R16 and that herpesvirus entry mediator (HVEM)-Ig, a fusion protein that blocks LIGHT, also inhibited disease development. Our results suggest that LT or LIGHT plays a critical role in the induction, rather than the effector, phase of the disease. [source] Key role for enkephalinergic tone in cortico,striatal,thalamic functionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Marylou V. Solbrig Whereas the role of dopaminergic tone in the cortico-striatal-thalamic system is well-established, the role of endogenous opioids in the function of this system is less understood. We show that Borna disease virus infection of adult rats results in an increase in preproenkephalin transcripts in the striatum of Borna-infected rats, a region important for forming coordinated sequential motor actions and in developing programmes of thought and motivation. Stereotypic behaviours and dyskinesias, the clinical hallmarks of infection in adult Lewis rats (BD rats), are accompanied by a disrupted pattern of immediate early gene c-fos activation in the motor thalamus, with significance for the breakdown in coordinated sequential motor actions. We also find increased preproenkephalin in infected cultured neuroblastoma and rat foetal glial cells. The expression pattern of enkephalin mRNA in vivo and in vitro suggest that increased enkephalin function is one of the neuropharmacological means by which Borna disease virus causes motor disease of animals and possibly cognitive and affective disease in man, and further suggest that enkephalins play a critical role in the maintenance of a balanced tone of activity in the cortico-basal ganglia-thalamo-cortical loops. [source] Strain differences in the behavioural outcome of neonatal ventral hippocampal lesions are determined by the postnatal environment and not genetic factorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2001Graham K. Wood Abstract It has been demonstrated that not only do rats neonatally lesioned in the ventral hippocampus (VH) develop behavioural hypersensitivity to amphetamine postpubertally, but also that the expression of the sensitivity is strain specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to significant increases in amphetamine-induced locomotion in postpubertal Fischer rats, but not in Lewis rats. However, as it is likely that the effect of strain differences are due to a combination of genetics and environment, we examined the contributions of the environment of the pups in determining the behavioural outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross-fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic acid. anova analysis of postpubertal amphetamine-induced locomotor data revealed a significant effect of the strain of the dams raising the pups but no effect of the strain of the pup. In addition, a post hoc analysis revealed that lesioned Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned controls. Observations of the maternal behaviour of Fischer and Lewis dams revealed significant differences in the frequency of arched-back nursing between the two strains. Interestingly, a correlation of the frequency of arched back nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned rats were significantly more affected by increases in arched-back nursing compared to the controls. The results suggest that the genetic background of the pups does not significantly affect the behavioural outcome following neonatal VH lesions; however, the results do suggest an important role of early environmental variables on the behavioural outcome of neonatal VH lesions. [source] Evidence for a female-specific effect of a chromosome 4 locus on anxiety-related behaviors and ethanol drinking in ratsGENES, BRAIN AND BEHAVIOR, Issue 6 2006L. F. Vendruscolo Previous studies using the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) led to the mapping of two quantitative trait loci, named Ofil1 (on chromosome 4 of the rat) and Ofil2 (on chromosome 7), for open-field inner locomotion, a behavioral index of anxiety. Studies using other strains showed that the region next to Ofil1 influences measures of not only anxiety but also ethanol consumption. In view of the high prevalence of psychiatric disorders such as anxiety and alcoholism, as well as the comorbidity between them, the present study was designed to better characterize the contribution of these two loci to complex emotional and consummatory responses. Rats deriving from an F2 intercross between the LEW and the SHR strains were selected according to their genotype at markers flanking the loci Ofil1 and Ofil2 and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating four genotypic combinations. These selected animals as well as purebred LEW and SHR rats of both sexes were submitted to a battery of tests including measures of locomotor activity, anxiety, sweet and bitter taste reinforcement and ethanol intake. Lewis rats displayed more anxiety-like behavior and less ethanol intake than SHR rats. Ofil1 (on chromosome 4) affected both the activity in the center of the open field and ethanol drinking in females only. These results suggest that Ofil1 contains either linked genes with independent influences on anxiety-related responses and ethanol drinking or a pleiotropic gene with simultaneous effects on both traits. [source] Recruitment of host progenitor cells in rat liver transplants,HEPATOLOGY, Issue 2 2009Zhaoli Sun Despite major histocompatibility complex incompatibility, liver transplants from Lewis rats to dark agouti (DA) rats survive indefinitely without immunosuppression, and the studies we report sought the mechanism(s) responsible for this. At 1 year, most of the liver reacted positively to host anti-DA antibody. When small (50%) grafts were transplanted, recruitment was more rapid because most of the organ assumed the host phenotype at 3 months. After transplantation, the Y chromosome was detected in the hepatocytes of XX to XY grafts by both in situ hybridization and polymerase chain reaction. Further, livers from transgenic Lewis rats carrying strong green fluorescent protein (GFP) markers lost the marker with time after transplantation to DA, GFP-negative hosts. Few liver cells contained the Y chromosome in syngeneic XX to XY liver grafts or when the hosts of Lewis XX to DA XY allografts were treated with cyclosporine A at 10 mg/kg/day. This dosage also impeded enlargement of the liver at 10 days. Using GFP-positive XX Lewis donors transplanted to GFP-negative XY DA hosts, we found little Y DNA in GFP-positive cells at 10 days. Host-derived OV-6,positive and c-kit,positive, albumin-positive cells were present at 3-10 days, but cells with the CD34 marker were less common and some clearly still had the donor phenotype at 10 days. Cells positive for chemokine cysteine-X-cysteine receptor-4 increased with time and were abundant 1 month after transplantation. We conclude: (1) extrahepatic cells can differentiate into liver tissues; (2) regenerative stimuli accelerate stem cell recruitment; (3) both regeneration and recruitment are impeded by cyclosporine A immunosuppression, and (4) donor GFP-positive cells contained little host Y chromosome after transplantation, suggesting that cell fusion was uncommon and, therefore, unlikely to be the mechanism leading to the changes in genotype and phenotype we observed. (HEPATOLOGY 2008.) [source] Gliotoxin, an inhibitor of nuclear factor-kappa B, attenuates peptidoglycan-polysaccharide-induced colitis in ratsINFLAMMATORY BOWEL DISEASES, Issue 3 2002Dr. Leo R. Fitzpatrick Abstract Gliotoxin is a fungal metabolite that has immunosuppressive properties. First, we determined if gliotoxin could inhibit bacterial peptidoglycan,polysaccharide-stimulated tumor necrosis factor-, production, as well as nuclear factor-kappa B (NF-,B), in a rat macrophage (NR8383) cell line. Next, the apoptosis-inducing potential of gliotoxin was also evaluated in this cell line. Finally, we evaluated whether gliotoxin could reduce peptidoglycan,polysaccharide-induced colitis in rats. Gliotoxin (2 mg/kg/day) was dosed from day 14 after the initial intramural colonic injection of peptidoglycan,polysaccharide until day 21. A gross colonic injury score, myeloperoxidase activity, and cytokine levels were all evaluated on day 21. Gliotoxin dose dependently inhibited cytokine production, as well as NF-,B, and also induced apoptosis in the NR8383 cell line. On day 21, gliotoxin significantly reduced gross colonic injury (adhesions, nodules, mucosal lesions) in rats. Gliotoxin-treated rats also had partially normalized biochemical indices of colitis, such as colonic cytokine levels. The colonic level of NF-,B was also partially normalized in gliotoxin treated rats. Gliotoxin also exhibited an antiarthritis effect in peptidoglycan,polysaccharide-treated rats. In summary, gliotoxin effectively attenuated the chronic reactivation phase of peptidoglycan,polysaccharide-induced colitis. This anticolitis effect may be related to the inhibition of NF-,B in Lewis rats. [source] Effect of cyclosporin A in Lewis rats in vivo and HeLa cells in vitroJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2002Andrea Sovcikova Abstract The aim of this study was to compare the effect of cyclosporin A (CsA) in inbred Lewis rats with published assessment of immunotoxicity in ,classical' outbred Wistar rats. A second purpose was to consider the contribution of a panel of in vitro assays in cell cultures when added to an immunotoxicity study in vivo. The in vivo effect of CsA was investigated in a 28-day subacute immunotoxicity study in male Lewis rats at three different concentrations: 1.25, 5 and 20 mg kg,1. The highest dose of CsA exceeded the maximum tolerated dose. A drop in body, spleen and popliteal lymph node weight of exposed animals displayed symptoms of toxicity. At a high toxic dose, haematological changes showed a decrease in the leucocyte count and in the percentage of lymphocytes, and an increase in the percentage of polymorphonuclear leucocytes. The haematocrit was significantly dose-dependently suppressed in all rats exposed to CsA. A similar dose-dependent depression of the mean cell volume of erythrocytes was found in rats given high and middle doses of CsA. The phagocytic activity of polymorphonuclear leucocytes and monocytes also was significantly dose-dependently suppressed. No significant changes in primary antibody response to sheep erythrocytes or in vitro proliferative response of spleen lymphocytes to mitogens were found in those rats. A battery of in vitro cytotoxicity methods was selected for the evaluation of metabolic and functional activity of subcellular organelles (mitochondria, lysosomes) and for the detection of drug-induced superoxide-mediated damage in HeLa cells. This cell line was chosen because it has a lower activity of superoxide dismutase (SOD) than normal cells and is sufficiently sensitive for the detection of the induction of oxygen radicals. The in vitro results indicated a direct relationship between CsA cytotoxicity and a change in the mitochondrial enzyme activity, as well as an induction of superoxide production. The results of the study indicated that a combination of selected in vivo and in vitro methods is an inexpensive way to obtain more complex information on cell status affected by xenobiotics. Copyright © 2002 John Wiley & Sons, Ltd. [source] Immunosuppression with FK506 Increases Bone Induction in Demineralized Isogeneic and Xenogeneic Bone Matrix in the RatJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2000Dr. Gregor Voggenreiter Abstract The aim of the present study was to investigate a systemic induction of bone formation in rats by immunosuppression with FK506 (1 mg/kg body weight intraperitoneally [ip]) in a model of osteoinduction of isogeneic and xenogeneic demineralized bone matrix (DBM) for a period of 28 days. In particular, alterations of in vitro cytokine synthesis and changes of lymphocyte subsets were studied. DBM was implanted intramuscularly in the abdominal wall of Lewis rats (seven per group). Blood was sampled on days ,7, 0, 7, and 28 for determination of in vitro tumor necrosis factor , (TNF-,) synthesis and lymphocyte subsets by flow cytometry (CD3+, CD4+, CD8+, CD45+, ED9+, and Ia+ antibodies). Ossicles of de novo formed bone and the tibias were removed on day 28 after double tetracycline labeling for histomorphometric analysis. Immunosuppression with FK506 significantly decreased lipopolysaccharide (LPS)-stimulated in vitro cytokine synthesis after 7 days and 28 days (p < 0.05). Compared with control animals FK506 treatment significantly increased the volume of induced bone in isogeneic (2.1 ± 0.3 mm3 vs. 10.8 ± 0.9 mm3) and xenogeneic (0 mm3 vs. 4.7 ± 0.8 mm3) DBM. Bone histomorphometry of the tibias revealed that immunosuppression increased both bone formation and bone resorption, accompanied by a significant reduction in the relative trabecular area (Tb.Ar). FK506 caused a decrease in the counts of CD8+ T cells probably because of destruction or dislocation of these cells. This suggests that the amount of CD8+ cells and the degree of T cell activation in terms of mean fluorescence intensity (MFI) may be associated with bone metabolism. In support of this, statistical analysis revealed a significant positive correlation between parameters of bone formation as well as bone resorption and the CD4+/CD8+ ratio. There was a significant negative correlation between parameters of remodeling of the metaphysis of the tibia and induced bone volume (BV), respectively, and MFI values of CD3+/Ia+ cells. These findings suggest an important role of T lymphocytes in bone formation and bone resorption in vivo. FK506 caused a marked increase of bone formation in DBM. However, the conclusion that immunosuppression increases fracture healing warrants further investigation. [source] Evaluation of blood vessel ingrowth in fibrin gel subject to type and concentration of growth factorsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9a 2009A. Arkudas Abstract Our aim was to quantitatively assess the angiogenetic effects of VEGF and bFGF immobilized in a fibrin-based drug delivery system in a suitable subcutaneous rat model. After evaluation of a suitable implantation technique (6 rats), four teflon isolation chambers containing fibrin gel matrices were implanted subcutaneously in an upside-down fashion on the back of 30 Lewis rats. The matrices consisted of 500 ,l fibrin gel with two different fibrinogen concentrations (10 mg/ml or 40 mg/ml fibrinogen) and 2 I.U./ml thrombin and contained VEGF and bFGF in five different concentrations (0 to 250 ng/ml each). At 3, 7 and 14 days after implantation, matrices were explanted and subjected to histological and morphometrical analysis. At 1 week, the volume of the fibrin clots was significantly smaller in the 100 and 250 ng/ml VEGF and bFGF groups in comparison to lower concentrated growth factors. At 1 and 2 weeks, the use of growth factors in low concentrations (25 ng/ml VEGF and bFGF) significantly increased the amount of fibrovascular tissue, average fraction of blood vessels and number of blood vessels at the matrix,host interface in comparison to growth factor-free controls. Higher concentrations were neither associated with further increase of tissue formation nor with increased sprouting of blood vessels in this model. This study demonstrates that fibrin gel-immobilized angioinductive growth factors efficiently stimulate generation of fibrovascular tissue and sprouting of blood vessels in a newly developed subcutaneous upside-down isolation chamber model with an optimum between 25 and 100 ng/ml. [source] Lipopolysaccharide-Induced Oestrogen Receptor Regulation in the Paraventricular Hypothalamic Nucleus of Lewis and Fischer RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2002L. Tonelli Abstract Oestrogen receptor (ER) regulation of gene transcription in neurosecretory and pituitary cells has been proposed as an important mechanism for increased hypothalamic-pituitary-adrenal (HPA) axis responses in females of several mammalian species, including humans. Inbred female Fischer (F344/N) and Lewis (LEW/N) rats have similar oestrogen levels, although Fischer rats exhibit hyper- and Lewis rats hypo-HPA axis responses. The blunted HPA axis response of Lewis rats has been associated with their blunted hypothalamic corticotropin releasing hormone (CRH) expression. To determine if the female CRH expression deficiency in Lewis rats is associated with defective ER expression and regulation, hypothalamic paraventricular nucleus (PVN) transcript levels of CRH and ER were determined under basal conditions and after immune challenge. Microdissected PVN were obtained from control and lipopolysaccharide (LPS) treated Lewis and Fischer rats and CRH, ER, and , mRNA levels were determined by semiquantitative reverse-transcriptase-polymerase chain reaction. In addition, ER, and , protein levels were determined by semiquantitative Western blots. ER, and , mRNA and protein levels in the PVN of control Fischer rats were significantly higher than in control Lewis rats. ER, and , mRNA and protein levels in Fischer rats were reduced by LPS administration at the time of maximal CRH mRNA levels but did not change in Lewis rats, an effect independent of oestrogen levels. These data indicate that defective neuroendocrine HPA axis responses are associated with defective ER expression and regulation in Lewis PVN despite oestrogen concentrations. [source] Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningocerebellitis in the Lewis rat: A model for cell-mediated autoimmune neuropathology,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2002Margit G. Proescholdt Abstract Neuronal elements are increasingly suggested as primary targets of an autoimmune attack in certain neurological and neuropsychiatric diseases. Type 1 cannabinoid receptors (CB1) were selected as autoimmune targets because they are predominantly expressed on neuronal surfaces in brain and display strikingly high protein levels in striatum, hippocampus, and cerebellum. Female Lewis rats were immunized with N-terminally acetylated peptides (50 or 400 ,g per rat) of the extracellular domains of the rat CB1 and killed at various time points. Subsequent evaluation using immunohistochemistry and in situ hybridization showed dense infiltration of immune cells exclusively within the cerebellum, peaking 12,16 days after immunization with the CB1 peptide containing amino acids 9,25. The infiltrates clustered in meninges and perivascular locations in molecular and granular cell layers and were also scattered throughout the CB1-rich neuropil. They consisted primarily of CD4+ and ED1+ cells, suggestive of cell-mediated autoimmune pathology. There were no inflammatory infiltrates elsewhere in the brain or spinal cord. The results show that neuronal elements, such as neuronal cell-surface receptors, may be recognized as antigenic targets in a cell-mediated autoimmune attack and, therefore, support the hypothesis of cell-mediated antineuronal autoimmune pathology in certain brain disorders. Published 2002 Wiley-Liss, Inc. [source] Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantationJOURNAL OF PINEAL RESEARCH, Issue 4 2009Zhanqing Li Abstract:, Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine,Tryptophan,Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39,71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity. [source] Ethanol-Induced Conditioned Taste Avoidance: Reward or Aversion?ALCOHOLISM, Issue 3 2009Chuang Liu Background:, Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. Methods:, In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague,Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Results:, Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. Conclusion:, The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose. [source] PERIPHERAL NERVOUS SYSTEM DEMYELINATION AND iNOS EXPRESSIONJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002Article first published online: 11 MAR 200 Conti G.1, Pasquale C.1, Rostami A.3, De Pol A.2, Galimberti D.1, Scarpini E.1, Baron P.L.1, Scarlato G.1 1 Milano Italy, 2 Modena, Italy, 3Philadelphia USA. Nitric oxide (NO), during CNS demyelination, is synthesised in inflammatory cells from L-arginine by the nitric oxide synthases (NOS). NO can subserve different functions, from cytotoxicity to neuroprotection and trigger either necrotic or apoptotic cell death. In this study we detected inducible form of NOS (iNOS) gene expression in experimental allergic neuritis (EAN), induced in Lewis rats by injection of "SP26," emulsified in complete Freund's adjuvant, which clinical, electrical, and pathological features resemble those of "Guillain-Barré" syndrome. Northern blot, single nerve fiber immmunostaining, and immuno-electron microscope showed that both iNOS mRNA and protein were induced in the PNS of EAN rats by day 14 after immunization, at the beginning of EAN clinical signs. However, with the same experimental procedures, we failed to find iNOS expression during Wallerian degeneration following nerve cut. These data support the hypothesis that iNOS regulation has an active role in cell-mediated demyelination. [source] Role Of Campylobacter Jejuni In Experimental Allergic Neuritis: A Morphological And Biochemical StudyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001M Laura Objective: The aim of the study was to evaluate if Campylobacter jejuni (C.j.) when used as an adjuvant would be able to produce a different form of Experimental Allergic Neuritis (EAN). We present here some preliminary results. Background: EAN is considered the in vivo model of Guillain-Barrè Syndrome (GBS), which is often preceded by c.j. infection. EAN can be induced in Lewis rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), an emulsion formed by oil-in-water and dead mycobacteria. An adjuvant is usually necessary for the induction of EAN because it enhances the immunogenicity of the antigen. Clinically EAN is characterized by an acute monophasic course and progressive tail and limb weakness. The pathological finding is represented by marked demyelination affecting the roots and the sciatic nerve. Methods: 4 Lewis rats were immunized with an emulsion containing 2 mg of bovine peripheral myelin and C.j. strain Penner 0:41 in incomplete Freund's adjuvant (IFA). They were compared to 4 controls immunized with the same amount of peripheral myelin in CFA. The clinical course of the disease and the histological pattern of the roots and the sciatic nerve were examined. Anti-peripheral myelin, anti-C.jejuni and anti-GM1 antibodies' reactivity was detected by an ELISA assay. A biochemical study was performed to test the role of cell- and humoral-mediated responses. Results: The Lewis rats immunized with the C.j. as an adjuvant showed a delayed onset and a milder course of disease. Pathology in the roots was characterized by predominant demyelination, whereas the sciatic nerve presented very little signs of damage. Conclusion: This serotype of C.j. appears to be a less effective adjuvant in inducing EAN rather than Mycobacteria. Further studies are necessary to elucidate the pathogenetic mechanisms involved in GBS. [source] Immunohistochemical and electron microscopic study of extrinsic hepatic reinnervation following orthotopic liver transplantation in ratsLIVER INTERNATIONAL, Issue 5 2001Tsuyoshi Takahashi Abstract:Background/Aims: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. Methods: Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). Results: Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. Conclusion: The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats. [source] Liver graft exposure to carbon monoxide during cold storage protects sinusoidal endothelial cells and ameliorates reperfusion injury in ratsLIVER TRANSPLANTATION, Issue 11 2009Atsushi Ikeda Hepatic ischemia/reperfusion (I/R) injury significantly influences short-term and long-term outcomes after liver transplantation (LTx). The critical step initiating the injury is known to include sinusoidal endothelial cell (SEC) alteration during the cold preservation period. As carbon monoxide (CO) has potent cytoprotective functions on vascular endothelial cells, this study examined if CO treatment of excised liver grafts during cold storage could protect SECs and ameliorate hepatic I/R injury. Rat liver grafts were preserved in University of Wisconsin (UW) solution containing 5% CO (CO-UW solution) for 18 to 24 hours and were transplanted into syngeneic Lewis rats. After 18 hours of cold preservation, SEC damage was evident with propidium iodide (PI) nuclear staining on SECs, and the frequency of PI+ SECs was significantly lower in grafts stored in CO-UW solution versus those stored in control UW solution. SEC protection with CO was associated with decreased intercellular cell adhesion molecule translocation and less matrix metalloproteinase release during cold preservation. After LTx with 18 hours of cold preservation, serum alanine aminotransferase levels and hepatic necrosis were significantly less in the CO-UW group than in the control UW group. With 24 hours of cold storage, 35% (7/20) survived with control UW solution, whereas the survival with CO-UW solution improved to 80% (8/10). These beneficial effects of CO-UW solution were associated with a significant reduction of neutrophil extravasation, down-regulation of hepatic messenger RNA for tumor necrosis factor alpha and intercellular cell adhesion molecule 1, and less hepatic extracellular signal-regulated kinase activation. Liver grafts from Kupffer cell,depleted donors or pseudogerm-free donors showed less SEC death during cold preservation, and CO-UW solution further reduced SEC death. In conclusion, CO delivery to excised liver grafts during cold preservation efficiently ameliorates SEC damage and hepatic I/R injury. Liver Transpl 15:1458,1468, 2009. © 2009 AASLD. [source] Effect of nondepleting anti-CD4 monoclonal antibody (Rib 5/2) plus donor antigen pretreatment in peripheral nerve allotransplantationMICROSURGERY, Issue 8 2002Vaishali B. Doolabh M.D. Peripheral nerve allotransplantation allows the reconstruction of injuries with long nerve gaps that are otherwise unsalvageable. In this study, the efficacy of anti-CD4 monoclonal antibody (mAb) combined with donor antigen pretreatment in prolonging the survival of short peripheral nerve allografts was investigated in a rodent model. Such an approach could potentially avoid the need for systemic immunosuppression and its concomitant morbidities. Buffalo rats received either nerve isografts or nerve allografts from Lewis rats. Untreated isograft and allograft groups were used as controls. Allograft recipients received either a single dose of RIB 5/2, a nondepleting anti-CD4 mAb, a single dose of Lewis splenocytes, or both antigen and RIB 5/2, 7 days prior to transplantation. Flow cytometric analysis verified that the T-lymphocyte population was maintained, while CD4 expression was downregulated by RIB 5/2. Histologic evaluation demonstrated better regeneration in the allograft recipients receiving both donor antigen and antibody, compared to recipients of untreated allografts or treatment with antigen or antibody alone. © 2002 Wiley-Liss, Inc. MICROSURGERY 22:329,334 2002 [source] Effects of simultaneous kidney-pancreaticoduodenal transplantation on diabetes-induced renal insufficiency in ratsMICROSURGERY, Issue 4 2001Jin Han Yoon M.D., Ph.D. An investigation of the functional and histological changes was done after en-bloc kidney-pancreaticoduodenal transplantation (kpdt) in the diabetes-induced, renal insufficient Lewis rats. For donor preparation, an end-to-side portocaval shunt was performed, and the aortic, vena caval segments, and ureter-bladder patch were obtained. They were anastomosed microsurgically to recipient's aorta, vena cava, and bladder in end-to-side fashion. Of 15 diabetes-induced kpdt rats, 14 survived. Two of the 14 surviving rats showed ischemic necrosis. The remaining 12 transplants showed well-preserved glomeruli and Langerhans islets for 5 months postoperatively. Biochemical data comparing diabetic and sham-operated rats (six rats each), six diabetic controls, and 12 kpdt rats showed no significant statistical difference at said observation period. The diabetes-induced kpdt rats showed improvement of following biochemical data: within 1 week postoperatively, the glucose level fell from 300 to 115 mg/dL; BUN level from >20 to <20 mg/dL; the creatinine level from 1.5 to <1.2 mg/dL. The insulin level returned to normal, 1.1 ng/mL, in 2 weeks. The results demonstrate that the kpdt model is an effective and successful operative technique in diabetic rats and may provide effective therapeutic methods for diabetes-induced renal insufficiency. © 2001 Wiley-Liss, Inc. MICROSURGERY 21:173,178 2001 [source] Adhesion molecule expression in experimental myositisMUSCLE AND NERVE, Issue 3 2002Tomoko Ito MD Abstract Experimental allergic myositis (EAM) in Lewis rats, induced with partially purified myosin, is regarded as a model of human polymyositis. To clarify the role of adhesion molecules in the pathogenesis of EAM in Lewis rats, we investigated intramysial expressions of the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the serum level of soluble ICAM-1 in EAM rats. All the EAM rat muscles had scattered inflammatory foci, as well as cell infiltration and necrosis, by week 4 after the initial immunization (i.e., day 0 after the last immunization). As compared with the control muscles, ICAM-1 and VCAM-1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium, and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers. ICAM-1 in the muscle extracts and sera from EAM rats increased on each test day, as compared with extracts from the normal controls. The values peaked on day 0 after the last immunization, then gradually decreased with time. ICAM-1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions (P = 0.032) and the histological scores (P = 0.005) on day 0, whereas there was no significance on days 3 and 7. These findings suggest that the adhesion molecules ICAM-1 and VCAM-1 increase in the early stage of EAM, and function in the initiation of the inflammatory process of myositis. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] Amelioration of experimental autoimmune encephalomyelitis in Lewis rats treated with fucoidanPHYTOTHERAPY RESEARCH, Issue 3 2010Heechul Kim Abstract We examined whether fucoidan affected the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in rats. EAE was induced in Lewis rats that were immunized with guinea-pig myelin basic protein (MBP) and complete Freund's adjuvant. Fucoidan (50,mg/kg, daily) was administered to rats with EAE intraperitoneally, either in the EAE induction phase from either 1 day before immunization to day 7 post-immunization (PI), or the effector phase from day 8 to 14 PI, to test which phase of rat EAE is affected by fucoidan treatment. The onset, severity and duration of EAE paralysis in the fucoidan-treated group in the days 8,14 PI-treated rats, but not in days ,1,7 PI-treated rats, were significantly delayed, suppressed and reduced, respectively, compared with the vehicle-treated controls. Treatment with fucoidan reduced the encephalitogenic response and TNF-, production during EAE. Moreover, the clinical amelioration coincided with decreased infiltration of inflammatory cells in the EAE-affected spinal cord. The ameliorative effect of fucoidan on clinical paralysis in EAE-affected rats may be mediated, in part, by the suppression of the autoreactive T cell response and inflammatory cytokine production. Copyright © 2009 John Wiley & Sons, Ltd. [source] Antigenic as Well as Nonantigenic Stimuli Induce Similar Middle Ear Responses in the Rat,THE LARYNGOSCOPE, Issue 2 2003Edith L. G. M. Tonnaer MSc Abstract Objectives/Hypothesis The observation that during otitis media many different types of micro-organisms have been cultured from effusions indicate that, once present in the middle ear cavity, most types of micro-organisms are able to trigger an inflammatory reaction leading to otitis media. The present study was designed to determine the middle ear response after injection of different substances into the middle ear cavity. Study Design To determine whether and to what extent an inflammatory response of the middle ear depends on the entering agent, the response in the tympanic cavity was studied by otomicroscopy and histological examination after inoculation of various substances. Methods Lewis rats were inoculated in transtympanic fashion either with live or heat-killed bacteria (pathogenic and nonpathogenic), Keyhole limpet hemocyanin, active charcoal, or saline. The mucosal response of the challenged middle ears was studied histologically. Results Irrespective of the inoculated substance, no essential differences in the mucosal response were found. The intensity of the inflammatory response was greater when live bacteria were inoculated. Conclusions The present study demonstrates that any substance reaching the middle ear cavity is likely to induce otitis media. These observations emphasize the role of the eustachian tube as "porte d'entrée" in the pathogenesis of this disorder. Determination of specific aspects of the eustachian tube involved in protection or in facilitating bacterial translocation will be important for the understanding of the pathogenesis of otitis media and the subsequent development of new therapeutic strategies. In addition, elucidation of bacterial factors involved in the process of colonization and translocation will be of equal importance. [source] Induction of Indoleamine 2,3-Dioxygenase by Gene Delivery in Allogeneic Islets Prolongs Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010H. Dellê Indoleamine 2,3-dioxygenase (IDO), an enzyme that plays a critical role in fetomaternal tolerance, exerts immunoregulatory functions suppressing T-cell responses. The aims of this study were to promote IDO expression in rat islets using a nonviral gene transfer approach, and to analyze the effect of the in vivo induction of IDO in a model of allogeneic islet transplantation. The IDO cDNA was isolated from rat placenta, subcloned into a plasmid and transfected into rat islets using Lipofectamine. The efficiency of transfection was confirmed by qRT-PCR and functional analysis. The in vivo effect of IDO expression was analyzed in streptozotocin-induced diabetic Lewis rats transplanted with allogeneic islets under the renal capsule. Transplantation of IDO-allogeneic islets reversed diabetes and maintained metabolic control, in contrast to transplantation of allogeneic nontransfected islets, which failed shortly after transplantation in all animals. Graft survival of allograft islets transfected with IDO transplanted without any immunosuppression was superior to that observed in diabetic rats receiving nontransfected islets. These data demonstrated that IDO expression induced in islets by lipofection improved metabolic control of streptozotocin-diabetic rats and prolonged allograft survival. [source] Resident Macrophages are Involved in Intestinal Transplantation-Associated Inflammation and Motoric Dysfunction of the Graft MuscularisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007N. Schaefer Gut manipulation and ischemia/reperfusion evoke an inflammatory response within the intestinal muscularis that contributes to dysmotility. We hypothesize that resident macrophages play a key role in initiating the inflammatory cascade. Isogenic small bowel transplantation was performed in Lewis rats. The impact of recovery of organs on muscularis inflammation was investigated by comparing cold whole-body perfusion after versus prior to recovery. The role of macrophages was investigated by transplantation of macrophage-depleted gut. Leukocytes were counted using muscularis whole mounts. Mediator expression was determined by real-time RT-PCR. Contractility was assessed in a standard organ bath. Both organ recovery and ischemia/reperfusion induced leukocyte recruitment and a significant upregulation in IL-6, MCP-1, ICAM-1 and iNOS mRNAs. Although organ recovery in cold ischemia prevented early gene expression, peak expression was not changed by modification of the recovery technique. Compared to controls, transplanted animals showed a 65% decrease in smooth muscle contractility. In contrast, transplanted macrophage-depleted isografts exhibited significant less leukocyte infiltration and only a 19% decrease in contractile activity. In summary, intestinal manipulation during recovery of organs initiates a functionally relevant inflammatory response within the intestinal muscularis that is massively intensified by the ischemia reperfusion injury. Resident muscularis macrophages participate in initiating this inflammatory response. [source] C4d Deposition and Clearance in Cardiac Transplants Correlates With Alloantibody Levels and Rejection in RatsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5p1 2006K. Minami Antibody-mediated rejection of human cardiac transplants is correlated with C4d deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We produced an antibody to rat C4d to study C4d deposition and clearance in Lewis rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was initiated after transplantation at a dose that inhibited graft rejection, antibody production and C4d deposition in unsensitized recipients. Blood transfusion elicited high levels of circulating IgG alloantibodies, predominantly of the complement-activating IgG2b subclass, that peaked 14 days after transplantation. At this time, macrophages accumulated in capillaries, and C4d deposits were diffuse and intense on arteries, capillaries and veins. Grafts that survived 90 days in sensitized recipients still had deposits of C4d that were associated with increased interstitial fibrosis and vasculopathy in arteries. Clearance of C4d was determined by retransplanting DA cardiac allografts from Lewis recipients back to DA recipients. C4d deposits were decreased to minimal levels within 5 days after retransplantation. Thus, C4d deposition is not limited to the capillaries, but extends throughout the arterial tree, and despite formation of a covalent bond, C4d is cleared within days. [source] Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo,ANNALS OF NEUROLOGY, Issue 5 2009Monika Bradl PhD Objective Severe inflammation and astrocyte loss with profound demyelination in spinal cord and optic nerves are typical pathological features of neuromyelitis optica (NMO). A diagnostic hallmark of this disease is the presence of serum autoantibodies against the water channel aquaporin-4 (AQP-4) on astrocytes. Methods We induced acute T-cell,mediated experimental autoimmune encephalomyelitis in Lewis rats and confronted the animals with an additional application of immunoglobulins from AQP-4 antibody,positive and ,negative NMO patients, multiple sclerosis patients, and control subjects. Results The immunoglobulins from AQP-4 antibody,positive NMO patients are pathogenic. When they reach serum titers in experimental animals comparable with those seen in NMO patients, they augment clinical disease and induce lesions in the central nervous system that are similar in structure and distribution to those seen in NMO patients, consisting of AQP-4 and astrocyte loss, granulocytic infiltrates, T cells and activated macrophages/microglia cells, and an extensive immunoglobulin and complement deposition on astrocyte processes of the perivascular and superficial glia limitans. AQP-4 antibody containing NMO immunoglobulin injected into naïve rats, young rats with leaky blood,brain barrier, or after transfer of a nonencephalitogenic T-cell line did not induce disease or neuropathological alterations in the central nervous system. Absorption of NMO immunoglobulins with AQP-4,transfected cells, but not with mock-transfected control cells, reduced the AQP-4 antibody titers and was associated with a reduction of astrocyte pathology after transfer. Interpretation Human anti,AQP-4 antibodies are not only important in the diagnosis of NMO but also augment disease and induce NMO-like lesions in animals with T-cell,mediated brain inflammation. Ann Neurol 2009;66:630,643 [source] Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transectionARTHRITIS & RHEUMATISM, Issue 8 2010Gregory D. Jay Objective To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury. Methods Unilateral ACL transection (ACLT) was performed in Lewis rats (n = 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 ,l/injection) of either phosphate buffered saline (PBS) (n = 9), human synoviocyte lubricin (200 ,g/ml; n = 9), rhPRG4 (200 ,g/ml; n = 9), or human SF lubricin (200 ,g/ml; n = 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O,fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI),modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured. Results Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricin, and human SF lubricin,treated animals were significantly lower than those in untreated animals (P = 0.005 and P = 0.002, respectively) and in PBS-treated animals (P = 0.002 and P < 0.001, respectively). Conclusion After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA. [source] | |||||||||||||||||||||||||||||||