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Sprague Dawley Rats (sprague + dawley_rat)
Kinds of Sprague Dawley Rats Selected AbstractsAge dependence of cataract induced by ultraviolet radiation-B in miceACTA OPHTHALMOLOGICA, Issue 2007Y ZHANG Purpose: To investigate for the C57BL/6 mouse if there is an age dependence of the dose-response function for in vivo UVR-300 nm induced forward light scattering in the lens. Methods: Each of four age groups of 25 mice aged 3, 6, 12, or 24 weeks were randomly distributed on five age group specific UVR-B dose levels. The dose levels selected for each age group were derived from the expected maximum tolerable dose (MTD). Expected MTDs were set to 1.9, 3.2, 4.8, and 6.0 kJ/m^2 for the 3, 12, and 24 weeks mice, respectively, based on published data for the albino Sprague Dawley rat. Each animal was unilaterally exposed to UVR-B to the pre-determined dose, delivered during 15 minutes. All mice were sacrificed two days after exposure and both lenses were extracted for; macroscopic imaging in incident illumination against a grid and in dark-field illumination, and measurement of intensity of forward light scattering. The difference of intensity of forward light scattering between the exposed and the contralateral not exposed lens was fitted against dose received using regression based on a second order polynomial model. Results: Two days after exposure, subcapsular opacities were observed in the exposed lenses from all dose groups except at 0 kJ/m^2. In all age groups, the difference of intensity of forward light scattering increased with increasing UVR-B dose. The increase was age dependent. Conclusions: In the pigmented C57BL/6 mouse, an increasing in vivo dose of UVR-300 nm induces an increasing intensity of forward light scattering that is age dependent in the age interval 3-24 weeks. This finding should be considered in future design of experiments on UVR-effects to the mouse lens. [source] Electrophoretic variants of cardiac myosin heavy chain-, in Sprague Dawley ratsELECTROPHORESIS, Issue 3 2004Peter J. Reiser Abstract Analysis of cardiac myosin revealed differences in gel electrophoretic migration patterns of the ,-isoform of myosin heavy chain, but not the ,-isoform, in Sprague Dawley rats. No differences in the migration patterns of the ,-or ,-isoforms were observed in other rat strains. Three electrophoretic migration patterns of the ,-isoforms were observed in individual rats: a slower migrating isoform alone (4% of all rats tested), a faster migrating isoform alone (55%), and both isoforms (41%). The isoform expression pattern was identical in all myocardial regions in each rat. Frequency of expression patterns suggests multiple gene sequences for ,-cardiac myosin heavy chain in Sprague Dawley rats. Sequence analysis of amplified regions of the Sprague Dawley and Brown Norway rat ,-myosin genes, specifically the 5'-untranslated region, exons 1,3, and associated introns, showed numerous single nucleotide polymorphisms in coding and noncoding regions, including putative regulatory sites in Sprague Dawley rats, but not in Brown Norway rats. All Sprague Dawley rats varied from Brown Norway rats and no heterogeneity was observed in Brown Norway rats. Several deletions and dimorphic positions were also observed. Dimorphic positions were evident on automated sequencing comparisons. The data indicate that at least two ,-myosin heavy chain isoforms exist in Sprague Dawley rats and these rats exhibit sequence diversity within that portion of the ,-myosin heavy chain gene reported in this study. [source] In vivo mutation assay based on the endogenous Pig-a locusENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2008Steven M. Bryce Abstract The product of the X-chromosome's Pig-a gene acts in the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, and is thereby essential for attaching certain proteins to the cell surface. The experiments described herein were designed to evaluate whether lack of GPI-anchored proteins could form the basis of an in vivo mutation assay. Specifically, we used a CD59-negative cell surface phenotype to denote Pig-a mutation. Besides anti-CD59-PE, two other fluorescent reagents were used: thiazole orange to differentiate mature erythrocytes, reticulocytes (RETs), and leukocytes; and anti-CD61 to resolve platelets. These experiments were performed with Sprague Dawley rats, and focused on two cell populations, total erythrocytes and RETs. The ability of the analytical method to enumerate CD59-negative erythrocytes was initially assessed with reconstruction experiments whereby mutant-mimicking cells were added to control bloods. Subsequently, female rats were treated on three occasions with the model mutagens ENU (100 mg/kg/day) or DMBA (40 mg/kg/day). Blood specimens were harvested at various intervals, as late as 6 weeks post-exposure. Considering all week 4,6 data, we found that CD59-negative cells ranged from 239 to 855 × 10,6 and 82 to 405 × 10,6 for ENU and DMBA, respectively. These values were consistently greater than those observed for negative control rats (18 ± 19 × 10,6). The elevated frequencies observed for the genotoxicant-exposed animals were usually higher for RETs compared to total erythrocytes. These data support the hypothesis that an efficient in vivo mutation assay can be developed around flow cytometric enumeration of erythrocytes and/or RETs that exhibit aberrant GPI-anchored protein expression. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Pulmonary responses of acute exposure to ultrafine iron particles in healthy adult ratsENVIRONMENTAL TOXICOLOGY, Issue 4 2003Ya-Mei Zhou Abstract As critical constituents of ambient particulate matter, transition metals such as iron may play an important role in health outcomes associated with air pollution. The purpose of this study was to determine the respiratory effects of inhaled ultrafine iron particles in rats. Sprague Dawley rats 10,12 weeks of age were exposed by inhalation to iron particles (57 and 90 ,g/m3, respectively) or filtered air (FA) for 6 h/day for 3 days. The median diameter of particles generated was 72 nm. Exposure to iron particles at a concentration of 90 ,g/m3 resulted in a significant decrease in total antioxidant power along with a significant induction in ferritin expression, GST activity, and IL-1, levels in lungs compared with lungs of the FA control or of animals exposed to iron particles at 57 ,g/m3. NF,B,DNA binding activity was elevated 1.3-fold compared with that of control animals following exposure to 90 ,g/m3 of iron, but this change was not statistically significant. We concluded that inhalation of iron particles leads to oxidative stress associated with a proinflammatory response in a dose-dependent manner. The activation of NF,B may be involved in iron-induced respiratory responses, but further studies are merited. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 227,235, 2003. [source] Production of a new model of slowly progressive Heymann nephritisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2003Arpad Z. Barabas Summary., A slowly progressive autoimmune kidney disease was induced in Sprague Dawley rats by subcutaneous injection of a chemically modified kidney antigen (rKF3), incorporated into Alum and Distemper complex vaccine, followed by subcutaneous injections of an aqueous preparation of the same antigen. Pathogenic autoantibodies developed, which reacted with fixed glomerular nephritogenic antigen. Subsequently, immunopathological events lead to chronic progressive immune complex glomerulonephritis and proteinuria. The slowly developing disease was morphologically and functionally similar to Heymann nephritis (HN). The damage observed in the kidneys of experimental animals at 8 weeks and at the end of the experiment was examined by direct fluorescent antibody test, histology and electron microscopy. The changes were similar to the typical lesions found in HN rat kidneys, but less severe. Animals became proteinuric from 17 weeks onward (instead of the usual 4,8 weeks). By the end of the experiment, at 8 months, 100% of the rats were proteinuric. This new experimental model of autoimmune kidney disease, which is not complicated by intraperitoneal deposition and retention of Freund's complete adjuvant and renal tubular antigens, allowed us to investigate the pathogenesis of the disease processes from a different aspect, and promises to be a useful and improved model for the investigation of future treatment options. [source] THE POTENTIAL OF TERMINALIA CATAPPA (TROPICAL ALMOND) SEED AS A SOURCE OF DIETARY PROTEINJOURNAL OF FOOD QUALITY, Issue 3 2004C.A. EZEOKONKWO ABSTRACT The nutritional value of Terminalia catappa seed as a source of dietary protein was investigated. The crude protein content of the seed was high (25.81%). The amino acid analysis showed a good pattern of the essential amino acids (EAA) (in g/16 g N) - leucine (7.32), isoleucine (3.58), valine (2.74), phenylalanine (3.04), tryptophan (0.9), methionine (1.48), lysine (3.39), threonine (2.94), histidine (2.96). Tyrosine (2.12) is the limiting amino acid. The protein quality of the seed was evaluated by in vivo bioassays using weanling male Sprague Dawley rats (50,60 g). The indices of protein quality measured include PER, BV, NPU and TD. There were positive correlation between PER and BV (r = 0.7105), PER and body weight gain (r = 0.9157), PER and nitrogen intake (r = 0.7428). The results showed that T. catappa seed protein has a good pattern of the EAA, is highly digestible, can support growth and positive nitrogen balance and thus has a high dietary protein quality. [source] The Long-Term Effects of Feeding Honey Compared with Sucrose and a Sugar-Free Diet on Weight Gain, Lipid Profiles, and DEXA Measurements in RatsJOURNAL OF FOOD SCIENCE, Issue 1 2008L. Chepulis ABSTRACT:, To determine whether honey and sucrose would have differential effects on weight gain during long-term feeding, 45 2-mo-old Sprague Dawley rats were fed a powdered diet that was either sugar-free or contained 7.9% sucrose or 10% honey ad libitum for 52 wk (honey is 21% water). Weight gain was assessed every 1 to 2 wk and food intake was measured every 2 mo. At the completion of the study blood samples were removed for measurement of blood sugar (HbA1c) and a fasting lipid profile. DEXA analyses were then performed to determine body composition and bone mineral densities. Overall weight gain and body fat levels were significantly higher in sucrose-fed rats and similar for those fed honey or a sugar-free diet. HbA1c levels were significantly reduced, and HDL-cholesterol significantly increased, in honey-fed compared with rats fed sucrose or a sugar free diet, but no other differences in lipid profiles were found. No differences in bone mineral density were observed between honey- and sucrose-fed rats, although it was significantly increased in honey-fed rats compared with those fed the sugar-free diet. [source] Habituation and Cross-Sensitization of Stress-Induced Hypothalamic-Pituitary-Adrenal Activity: Effect of Lesions in the Paraventricular Nucleus of the Thalamus or Bed Nuclei of the Stria TerminalisJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2002G. A. Fernandes Abstract Habituation of the hypothalamic-pituitary-adrenal (HPA) response to chronic intermittent restraint stress (30 min/day for 15 days) and the cross-sensitization to a heterotypic stress [i.p. lipopolysaccharide (LPS)] were investigated in intact male Sprague Dawley rats, and in rats bearing quinolinic acid lesions to the medial anterior bed nuclei of the stria terminalis (BST) or anterior region of the paraventricular nucleus of the thalamus (PVT). In intact animals, a single period of restraint increased plasma corticosterone levels at 30 min and led to an increase in corticotropin-releasing hormone (CRH) mRNA levels in the PVN at 3 h. LPS had a smaller effect on corticosterone and more variable effect on CRH mRNA. Chronic intermittent restraint stress caused a decrease in body weight and increase in adrenal weights, with concomitant increase in basal corticosterone levels. These animals also displayed marked habituation of the corticosterone and CRH mRNA responses to the homotypic stress of restraint, but no loss of the corticosterone response to the heterotypic stress of LPS and a cross-sensitization of the CRH mRNA response. This pattern of stress responses in control and chronically stressed animals was not significantly affected by lesions to the PVT or BST, two areas which have been implicated in the coping response to stress. Thus, these data provide evidence for independent adaptive mechanisms regulating HPA responses to psychological and immune stressors, but suggest that neither the medial anterior BST nor the anterior PVT participate in the mechanisms of habituation or cross-sensitization. [source] Fasting is neuroprotective following traumatic brain injury,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2008Laurie M. Davis Abstract To determine the neuroprotective effect of fasting after traumatic brain injury (TBI) and to elucidate the potential underlying mechanisms, we used a controlled cortical impact (CCI) injury model to induce either a moderate or a severe injury to adult male Sprague Dawley rats. Tissue-sparing assessments were used to determine the level of neuroprotection of fasting, hypoglycemia (insulin 10 U), or ketone (1.66 mmoles/kg/day or 0.83 mmoles/kg/day; D-beta-hydroxtbutyrate) administration. Mitochondrial isolation and respiratory studies were utilized to determine the functionality of mitochondria at the site of injury. We also investigated biomarkers of oxidative stress, such as lipid/protein oxidation, reactive oxygen species (ROS) production, and intramitochondrial calcium load, as a secondary measure of mitochondrial homeostasis. We found that fasting animals for 24 hr, but not 48 hr, after a moderate (1.5 mm), but not severe (2.0 mm), CCI resulted in a significant increase in tissue sparing. This 24-hr fast also decreased biomarkers of oxidative stress and calcium loading and increased mitochondrial oxidative phosphorylation in mitochondria isolated from the site of injury. Insulin administration, designed to mimic the hypoglycemic effect seen during fasting did not result in significant tissue sparing after moderate CCI injury and in fact induced increased mortality at some injection time points. However, the administration of ketones resulted in increased tissue sparing after moderate injury. Fasting for 24 hr confers neuroprotection, maintains cognitive function, and improves mitochondrial function after moderate (1.5 mm) TBI. The underlying mechanism appears to involve ketosis rather than hypoglycemia. © 2008 Wiley-Liss, Inc. [source] Brain-derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplantJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2002G.W. Hiebert Abstract Previous experiments from our laboratory have shown that application of brain-derived neurotrophic factor (BDNF) to the red nucleus or the motor cortex stimulates an increase in the expression of regeneration-associated genes in rubrospinal and corticospinal neurons. Furthermore, we have previously shown that BDNF application stimulates regeneration of rubrospinal axons into a peripheral graft after a thoracic injury. The current study investigates whether application of BDNF to the motor cortex will facilitate regeneration of corticospinal neurons into a peripheral nerve graft placed into the thoracic spinal cord. In adult Sprague Dawley rats, the dorsal columns and the corticospinal tract between T9 and T10 were ablated by suction, and a 5-mm-long segment of predegenerated tibial nerve was autograft implanted into the lesion. With an osmotic pump, BDNF was infused directly into the parenchyma of the motor cortex for 14 days. Growth of the corticospinal tract into the nerve graft was then evaluated by transport of an anterograde tracer. Anterogradely labeled corticospinal fibers were not observed in the peripheral nerve graft in animals treated with saline or BDNF. Serotinergic and noradrenergic fibers, as well as peripheral sensory afferents, were observed to penetrate the graft, indicating the viability of the peripheral nerve graft as a permissive growth substrate for these specific fiber types. Although treatment of the corticospinal fibers with BDNF failed to produce regeneration into the graft, there was a distinct increase in the number of axonal sprouts rostral to the injury site. This indicates that treatment of corticospinal neurons with neurotrophins, e.g., BDNF, can be used to enhance sprouting of corticospinal axons within the spinal cord. Whether such sprouting leads to functional recovery after spinal cord injury is currently under investigation. © 2002 Wiley-Liss, Inc. [source] Induction of a neoarthrosis by precisely controlled motion in an experimental mid-femoral defectJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2002Dennis M. Cullinane Bone regeneration during fracture healing has been demonstrated repeatedly, yet the regeneration of articular cartilage and joints has not yet been achieved. It has been recognized however that the mechanical environment during fracture healing can be correlated to the contributions of either the endochondral or intramembranous processes of bone formation, and to resultant tissue architecture. Using this information, the goal of this study was to test the hypothesis that induced motion can directly regulate osteogenic and chondrogenic tissue formation in a rat mid-femoral bone defect and thereby influence the anatomical result. Sixteen male Sprague Dawley rats (400 ± 20 g) underwent production of a mid-diaphyseal, non-critical sized 3.0 mm segmental femoral defect with rigid external fixation using a custom designed four pin fixator. One group of eight animals represented the controls and underwent surgery and constant rigid fixation. In the treatment group the custom external fixator was used to introduce daily interfragmentary bending strain in the eight treatment animals (12°s angular excursion), with a hypothetical symmetrical bending load centered within the gap. The eight animals in the treatment group received motion at 1.0 Hz, for 10 min a day, with a 3 days on, one day off loading protocol for the first two weeks, and 2 days on, one day off for the remaining three weeks. Data collection included histological and immunohistological identification of tissue types, and mean collagen fiber angles and angular conformity between individual fibers in superficial, intermediate, and deep zones within the cartilage. These parameters were compared between the treatment group, rat knee articular cartilage, and the control group as a structural outcome assessment. After 35 days the control animals demonstrated varying degrees of osseous union of the defect with some animals showing partial union. In every individual within the mechanical treatment group the defect completely failed to unite. Bony arcades developed in the experimental group, capping the termini of the bone segments on both sides of the defect in four out of six animals completing the study. These new structures were typically covered with cartilage, as identified by specific histological staining for Type II collagen and proteoglycans. The distribution of collagen within analogous superficial, intermediate, and deep zones of the newly formed cartilage tissue demonstrated preferred fiber angles consistent with those seen in articular cartilage. Although not resulting in complete joint development, these neoarthroses show that the induced motion selectively controlled the formation of cartilage and bone during fracture repair, and that it can be specifically directed. They further demonstrate that the spatial organization of molecular components within the newly formed tissue, at both microanatomical and gross levels, are influenced by their local mechanical environment, confirming previous theoretical models. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Smoke Exposure Exacerbates an Ethanol-Induced Defect in Mucociliary Clearance of Streptococcus pneumoniaeALCOHOLISM, Issue 5 2005Elizabeth A. Vander Top Background: Alcoholics and smokers are particularly susceptible to pulmonary infections caused by Streptococcus pneumoniae, the pneumococcus. Infection begins when pneumococci colonizing the nasopharynx are aspirated into the lower respiratory tract. The major host defense against this movement is the mucociliary clearance apparatus. Both cigarette smoke and ethanol (EtOH) exposure alter ciliary beating and protein kinase activity in the respiratory mucosa in vitro, but their effects on bacterial clearance in the intact animal have not been determined. Methods: Male Sprague Dawley rats were exposed twice daily for 12 weeks to either the smoke generated from 30 cigarettes (smoke,exposed) or room air (sham,exposed). For the last five weeks of smoke exposure, the rats were fed Lieber-DeCarli liquid diets containing 0%, 16%, 26%, or 36% EtOH calories. The rats then were infected intranasally with S. pneumoniae, and movement of the organisms into the lower respiratory tract was quantified by plate counts of the tracheas and lungs 4 hr later. Ciliary beat frequency (CBF) analysis was performed on tracheal ring explants from each animal before and after stimulation with the ,-agonist isoproterenol, and tracheal epithelial cell protein kinase C (PKC) activity was measured. Results: Ingestion of any of the EtOH-containing diets resulted in a dose-dependent increase in movement of S. pneumoniae into the rats' lungs. This EtOH-induced defect was augmented further by concurrent smoke exposure, although smoke exposure alone had little effect on S. pneumoniae movement. Smoke, but not EtOH exposure, activated tracheal epithelial cell PKC. Increased movement of organisms into lungs correlated with a decrease in CBF and loss of the ciliary response to isoproterenol. Conclusion: EtOH ingestion in our model facilitated movement of S. pneumoniae into rats' lungs, a phenomenon exacerbated by concurrent smoke exposure. Furthermore, the organism's movement into the lungs correlated with a blunting of the rats' ciliary response to an established stimulus. Defects in mucociliary clearance thus may be one cause of the increased risk of pneumococcal infections in people who abuse alcohol, particularly if they also smoke. [source] Effects of Light and Dark Beer on Hepatic Cytochrome P-450 Expression in Male Rats Receiving Alcoholic Beverages as Part of Total Enteral NutritionALCOHOLISM, Issue 5 2005Mats Hidestrand Background: Alcoholic beverages contain many congeners in addition to ethanol. Therefore, consumption of alcoholic beverages may have considerably different effects on expression of hepatic microsomal monooxygenases than the relatively selective induction of cytochrome P-450 (CYP) 2E1 observed after consumption of pure ethanol. Methods: In the current study, we compared the effects of two beers: lager (a light roasted beer) and stout (a dark roasted beer) with those of an equivalent amount of pure ethanol on hepatic CYP expression. Beer or pure ethanol was part of a complete total enteral nutrition diet that was infused intragastrically into male Sprague Dawley rats for 21 days. At the end of the infusion period, rats were euthanized, and liver and intestinal microsomes were prepared. Expression and activity of CYP1A1/2, CYP2B1, CYP2E1, CYP3A, and CYP4A were assessed by Western immunoblotting and by using CYP enzyme,specific substrates, respectively. Results: mRNA and protein levels of CYP4A1 were elevated only in stout-treated animals. However, lauric acid 12-hydroxylase activity (a CYP4A-specific activity) was reduced (p, 0.05) in microsomes from lager- and stout-fed rats. After oxidation with potassium ferricyanide, this activity was significantly increased in microsomes from stout-fed animals. The relative expression of CYP2E1 and CYP2B1 and the activities toward p -nitrophenol, pentoxyresorufin, or benzyloxyresorufin did not differ between beers or compared with pure ethanol or controls. However, the mean expression of CYP1A2, CYP3A, and CYP4A apoproteins was greater in liver microsomes from stout-infused rats than in those from lager-infused rats, ethanol-infused rats, and diet controls (p, 0.05). In addition, although no significant differences were observed in ethoxyresorufin O-dealkylase (EROD), methoxyresorufin O-dealkylase (MROD), midazolam, or testosterone hydroxylase activities between groups, stout-infused rats had greater hepatic microsomal erythromycin N -demethylase activity than other groups (p, 0.05). Conclusions: Stout contains components other than ethanol that interact in a complex fashion with the monooxygenase system. [source] Chronic Ethanol-Induced Subtype- and Subregion-Specific Decrease in the mRNA Expression of Metabotropic Glutamate Receptors in Rat HippocampusALCOHOLISM, Issue 9 2004Agnes Simonyi Background: Chronic ethanol consumption is known to induce adaptive changes in the hippocampal glutamatergic transmission and alter NMDA receptor binding and subunit expression. Metabotropic glutamate (mGlu) receptors have been shown to function as modulators of neuronal excitability and can fine tune glutamatergic transmission. This study was aimed to determine whether chronic ethanol treatment could change the messenger RNA (mRNA) expression of mGlu receptors in the hippocampus. Methods: Male Sprague Dawley® rats were fed a Lieber-DeCarli liquid diet with 5% (w/v) ethanol or isocaloric amount of maltose for 2 months. Quantitative in situ hybridization was carried out using coronal brain sections through the hippocampus. Results: The results revealed decreases in mRNA expression of several mGlu receptors in different subregions of the hippocampus. In the dentate gyrus, mGlu3 and mGlu5 receptor mRNA levels were significantly lower in the ethanol-treated rats than in the control rats. In the CA3 region, the mRNA expression of mGlu1, mGlu5, and mGlu7 receptors showed substantial decreases after ethanol exposure. The mGlu7 receptor mRNA levels were also declined in the CA1 region and the polymorph layer of the dentate gyrus. No changes were found in mRNA expression of mGlu2, mGlu4, and mGlu8 receptors. Conclusions: Considering the involvement of hippocampal mGlu receptors in learning and memory processes as well as in neurotoxicity and seizure production, the reduced expression of these receptors might contribute to ethanol withdrawal-induced seizures and also may play a role in cognitive deficits and brain damage caused by long-term ethanol consumption. [source] Acute Alcohol Intoxication During Hemorrhagic Shock: Impact on Host Defense From InfectionALCOHOLISM, Issue 4 2004K. L. Zambell Abstract: Background: Acute alcohol intoxication is a frequent underlying condition associated with traumatic injury. Our studies have demonstrated that acute alcohol intoxication significantly impairs the immediate hemodynamic, metabolic, and inflammatory responses to hemorrhagic shock. This study investigated whether acute alcohol intoxication during hemorrhagic shock would alter the outcome from an infectious challenge during the initial 24 hr recovery period. Methods: Chronically catheterized male Sprague Dawley® rats were randomized to acute alcohol intoxication (EtOH; 1.75 g/kg bolus followed by a constant 15 hr infusion at 250,300 mg/kg/hr) or isocaloric isovolemic dextrose infusion (dex; 3 ml + 0.375 ml/hr). EtOH and dex were assigned to either fixed-volume (50%) hemorrhagic shock followed by fluid resuscitation with Ringer's lactate (EtOH/hem, dex/hem) or sham hemorrhagic shock (EtOH/sham, dex/sham). Indexes of circulating neutrophil function (apoptosis, phagocytosis, oxidative burst) were obtained at baseline, at completion of hemorrhagic shock, and at the end of fluid resuscitation. Bacterial clearance, lung cytokine expression, and myeloperoxidase activity were determined at 6 and 18 hr after an intratracheal challenge with Klebsiella pneumoniae (107 colony-forming units). Results: Mean arterial blood pressure was significantly lower in acute alcohol intoxication-hemorrhagic shock animals throughout the hemorrhagic shock. In sham animals, acute alcohol intoxication alone did not produce significant changes in neutrophil apoptosis or phagocytic activity but significantly suppressed phorbol myristic acid (PMA)-stimulated oxidative burst. Hemorrhagic shock produced a modest increase in neutrophil apoptosis and suppression of neutrophil phagocytic capacity but significantly suppressed PMA-stimulated oxidative burst. Acute alcohol intoxication exacerbated the hemorrhagic shock-induced neutrophil apoptosis and the hemorrhagic shock-induced suppression of phagocytosis without further affecting PMA-stimulated oxidative burst. Fluid resuscitation did not restore neutrophil phagocytosis or oxidative burst. Acute alcohol intoxication decreased (,40%) 3-day survival from K. pneumoniae in hemorrhagic shock animals, impaired bacterial clearance during the first 18 hr postinfection, and prolonged lung proinflammatory cytokine expression. Conclusions: These results demonstrate that the early alterations in metabolic and inflammatory responses to hemorrhagic shock produced by acute alcohol intoxication are associated with neutrophil dysfunction and impaired host response to a secondary infectious challenge leading to increased morbidity and mortality. [source] Immunohistochemical Characterization of Hepatic Malondialdehyde and 4-Hydroxynonenal Modified Proteins During Early Stages of Ethanol-Induced Liver InjuryALCOHOLISM, Issue 6 2003Brante P. Sampey Background: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. Methods: Female Sprague Dawley® rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. Results: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. Conclusions: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events. [source] Ethanol Exposure Enhances Apoptosis Within the TestesALCOHOLISM, Issue 10 2000Qianlong Zhu Background: Chronic ethanol abuse causes testicular atrophy and male infertility in alcoholic men. It is well known that ethanol exposure disrupts the hypothalamic-pituitary-gonadal axis, adversely affects the secretory function of Sertoli cells, and produces oxidative stress within the testes. It is still not clear what cellular mechanisms are responsible for the morphologic alteration of the testes that results in a reduction of testicular mass as a consequence of ethanol exposure. The hypothesis tested was that ethanol enhances apoptosis of testicular germ cells. Methods: In the experiments of chronic ethanol exposure, male Sprague Dawley® rats (Harlan Sprague Dawley, Inc., Indianapolis, IN) were fed Liber-Decarlie liquid diet for 9 weeks. In the experiments of acute ethanol exposure, a small volume of 20% ethanol solution was administered by intratesticular injection. Both 3,-end labeling of isolated testicular deoxyribonucleic acid (DNA) and labeling of apoptotic cells in situ by the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5,-triphosphate nick end-labeling method were used to determine apoptosis rates within the testes. The expression of proteins involved in apoptosis was assessed by reverse transcription-polymerase chain reaction and by Western blotting. Results: The testes of rats that were fed an ethanol-containing liquid diet had more testicular DNA fragmentation than did those of animals that were fed an isocaloric control diet. Ethanol increased the number of apoptotic spermatogonia as well as spermatocytes. Direct intratesticular injections of ethanol solution enhanced testicular DNA fragmentation, suggesting an increase in apoptosis. Moreover, Fas ligand levels were increased within the testes of rats that were chronically fed ethanol. In vitro, ethanol treatment of cultured Sertoli cells enhanced the production of Fas ligand. In addition, testicular levels of p53 messenger ribonucleic acid were increased in rats that were chronically fed ethanol. Conclusions: All of these observations suggest that ethanol enhances testicular germ cell apoptosis. [source] Effect of Chronic Alcohol Consumption on Total Plasma Homocysteine Level in RatsALCOHOLISM, Issue 3 2000Felix Stickel Background: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6, Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcoholrelated hyperhomocysteinemia. Methods: In the present study, 10 male Sprague Dawley® rats were fed ethanol-containing Lieber- DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin. Results: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5,-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 ± 4.63 ,mol/liter,p < 0.01) compared to the nonalcohol group (10.73 ± 2.76 ,mol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels. Conclusions: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion. [source] Expression of the ,-adhesin part of HRgpA in Sprague Dawley rats induces a specific antibody responseMOLECULAR ORAL MICROBIOLOGY, Issue 2 2004K. S. Vĺgnes The ,-adhesin part of the Porphyromonas gingivalis W50 (ATCC 53978) protease HRgpA was cloned in an eukaryotic expression vector and expressed in COS-7 cells. The monoclonal antibody MAb (61BG1.3), specific for the hemagglutinating domain of ,-adhesin, recognized the expressed ,-adhesin in the transfected cells both by immunoblot and immunofluorescence. Sprague Dawley rats were immunized intramuscularly with ,-adhesin encoding expression plasmid and expression plasmid without ,-adhesin insert. Skeletal muscle tissue at the site of immunization in the ,-adhesin immunized animals was shown to express this protein. The immunization induced a ,-adhesin-specific antibody response. Sera from the immunized animals were tested for hemagglutination inhibiting activity. Due to high natural inhibiting activity in all rat sera tested, no increased hemagglutination inhibition was detected in sera from the ,-adhesin immunized animals. [source] Disease Stage Characterization of Hepatorenal Fibrocystic Pathology in the PCK Rat Model of ARPKDTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2010Stephen B. Mason Abstract The rat Pck gene is orthologous to the human PKHD1 gene responsible for autosomal recessive polycystic kidney disease (ARPKD). Both renal and hepatic fibrocystic pathology occur in ARPKD. Affected humans have a variable rate of progression, from morbidly affected infants to those surviving into adulthood. This study evaluated the PCK rat, a model of slowly progressive ARPKD. This model originated in Japan and was rederived to be offered commercially by Charles River Laboratories (Wilmington, MA). Previous studies have described the basic aspects of PCK pathology from privately held colonies. This study provides a comprehensive characterization of rats from those commercially available. Rats were bred, maintained on a 12:12 hr light/dark cycle, fed (7002 Teklad), and water provided ad libitum. Male and female rats were evaluated from 4 through 35 weeks of age with histology and serum chemistry. As the hepatorenal fibrocystic disease progressed beyond 18 weeks, the renal pathology (kidney weight, total cyst volume) and renal dysfunction (BUN and serum creatinine) tended to be more severe in males, whereas liver pathology (liver weight as % of body weight and hepatic fibrocystic volume) tended to be more severe in females. Hyperlipidemia was evident in both genders after 18 weeks. Bile secretion was increased in PCK rats compared with age-matched Sprague Dawley rats. The PCK is an increasingly used orthologous rodent model of human ARPKD. This characterization study of hepatorenal fibrocystic pathology in PCK rats should help researchers select stages of pathology to study and/or monitor disease progression during their longitudinal studies. Anat Rec 293:1279,1288, 2010. © 2010 Wiley-Liss, Inc. [source] Vibration Causes Acute Vascular Injury in a Two-Step Process: Vasoconstriction and Vacuole DisruptionTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2008Sandya R. Govindaraju Abstract Hand,arm vibration syndrome is a vasospastic and neurodegenerative occupational disease. In the current study, the mechanism of vibration-induced vascular smooth muscle cell (SMC) injury was examined in a rat-tail vibration model. Tails of male Sprague Dawley rats were vibrated continuously for 4 hr at 60 Hz, 49 m/s2 with or without general anesthesia. Ventral tail arteries were aldehyde fixed and embedded in epoxy resin to enable morphological analysis. Vibration without anesthesia caused vasoconstriction and vacuoles in the SMC. Anesthetizing rats during vibration prevented vasoconstriction and vacuole formation. Exposing tail arteries in situ to 1 mM norepinephrine (NE) for 15 min induced the greatest vasoconstriction and vacuolation. NE induced vacuoles were twice as large as those formed during vibration. When vibrated 4 hr under anesthesia after pretreatment with NE for 15 min, the SMC lacked vacuoles and exhibited a longitudinal banding pattern of dark and light staining. The extracellular matrix was filled with particulates, which were confirmed by electron microscopy to be cellular debris. The present findings demonstrate that vibration-induced vasoconstriction (SMC contraction) requires functioning central nervous system reflexes, and the physical stress of vibration damages the contracted SMC by dislodging and fragmenting SMC vacuoles. Anat Rec, 291:999,1006, 2008. © 2008 Wiley-Liss, Inc. [source] The Influence of Cannulation Technique on Blood Flow to the Brain in Rats Undergoing Cardiopulmonary Bypass: A Cautionary "Tail"ARTIFICIAL ORGANS, Issue 6 2010Terence Gourlay Abstract Recently, there has been an increase in the use of rat models of cardiopulmonary bypass (CPB) for research purposes. Much of this work has focused on cerebral injury associated with CPB. Many of these studies employ a peripheral cannulation approach, often utilizing the caudal artery and internal or external jugular vein. The aim of the present study was to establish whether there is any alteration in blood flow to the brain associated with the use of different cannulation routes. Twenty-four adult male Sprague Dawley rats were allocated to one of three study groups: Group 1,caudal artery return, Group 2,open-chest aortic return, and Group 3,nonbypass control group. Colored microspheres were injected into all animals at four time points (postinduction, initiation of bypass, midbypass, and end bypass). After the termination of each experiment, the brains were excised, the tissue was digested, the microspheres were harvested, and the global blood flow to the brain was assessed using the reference flow method. There was a significant reduction in blood flow to the brain between both bypass groups and the control group. Additionally, cerebral blood flow was significantly lower in the caudal return group than in the aortic return group. There is a significant drop in blood flow to the brain associated with the initiation and continuation of CPB when compared to non-CPB controls. These results also confirm a considerable cerebral hypoperfusion associated with the peripheral cannulation technique, and suggest that peripheral bypass may exaggerate the influence CPB has on cerebral injury. This technique must therefore be employed with caution. [source] Gene expression in arcuate nucleus-median eminence of rats treated with leptin or ciliary neurotrophic factorBIOFACTORS, Issue 2 2007Suresh Ambati Abstract Ciliary neurotrophic factor (CNTF) and leptin are cytokine-like hormones and act on their corresponding receptors in the hypothalamic arcuate nucleus (ARC). The present study was designed to assess effects of intracerebroventricular (ICV) injection of leptin and CNTF on gene expression in micropunched hypothalamic arcuate nucleus-median eminence (ARCME) complex samples from rats. Male Sprague Dawley rats were implanted with lateral cerebroventricular cannulas for administration of control, 10 ,g/d leptin or 5 ,g/d CNTF for four days. Real-time Taqman RT-PCR was used to quantitatively compare the mRNA levels of selected genes in the ARC-ME complex. Leptin and CNTF increased ARC-ME mRNA levels of signal transducer and activator of transcription 3 (STAT3) by 64.5 and 124.7% (p < 0.01), suppressor of cytokine signaling 3 (SOCS3) by 258.9 and 1063.9% (p < 0.01), cocaine and amphetamine regulated transcript (CART) by 102.7 and 123.1% (p < 0.01), and proopiomelanocortin (POMC2) by 374.1 and 264.9% (p < 0.01), respectively. Leptin increased growth hormone releasing hormone (GHRH) by 309.9% (p < 0.01), while CNTF increased janus kinase 2 (JAK2) mRNA by 31.7% (p < 0.01) and decreased gonadotropin releasing hormone 1 (GNRH1) by 59.7% (p < 0.01), mitogen activated protein kinase 1 (MAPK1) by 19.4% (p < 0.05) and tyrosine hydroxylase (TH) by 74.5% (p < 0.05). Significant reduction in daily food intake and body weights by both the treatments was observed. Also, decrease in weights of fat pads was concomitant with lowered serum insulin and leptin levels. Our findings show that leptin and CNTF engage both convergent and divergent pathways involved in feeding, cellular signaling, inflammation, and other related regulatory systems. [source] Investigation of the potential pharmacokinetic and pharmaco-dynamic drug interaction between AHN 1-055, a potent benztropine analog used for cocaine abuse, and cocaine after dosing in rats using intracerebral microdialysisBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2006Sangeeta Raje Abstract Purpose. AHN 1-055, a benztropine (BZT) analog, binds with high affinity to the dopamine transporter (DAT), possesses behavioral, pharmacokinetic (PK) and brain microdialysate dopamine (DA) profiles distinct from cocaine. Accordingly, the objectives of this study were to evaluate the pharmacokinetics and dopamine release of AHN 1-055, in the presence of cocaine. Methods. Male Sprague Dawley rats (,300 g) were administered 5 mg/kg of AHN 1-055 and cocaine i.v. and blood and brain samples were collected over 36 h. In addition, dialysis probes were stereotaxically implanted into the nucleus accumbens and extracellular fluid (ECF) DA levels were measured. PK and PD models were used to describe the relationship between the AHN 1-055, cocaine and DA levels. Results. No significant (p<0.05) differences were found in the PK parameters of AHN 1-055 alone (Vdss=18.7 l/kg, Cl=1.8 l/h/kg and t1/2=7.69 h) or AHN 1-055 with cocaine (Vdss=17.4 l/kg, Cl=1.9 l/h/kg and t1/2=6.82 h). The brain-to-plasma (B/P) ratios (B/PAHN 1,055=4.8 vs B/Pwith cocaine=4.4) and half-lives (t1/2(AHN 1,055)=6.2 h vs t1/2(cocaine)=5.6 h for AHN 1-055 alone and with cocaine were comparable. AHN 1-055 DA profiles were significantly different after co-administration with cocaine. There were no differences in the IC50 for AHN 1-055, with cocaine, however, the IC50 for cocaine was significantly reduced with AHN 1-055. Conclusions. The PK parameters of AHN 1-055 were not changed, however, the effect on DA levels was affected when cocaine was administered with AHNDA profile is affected when dosed with cocaine. This latter effect is a desirable attribute in the development of a medication as a potential substitute therapeutic medication for the treatment of cocaine abuse. Copyright © 2006 John Wiley & Sons, Ltd. [source] Periodically Discontinuous Induction of Bone Marrow Stem Cells toward Osteogenic Differentiation in VitroBIOTECHNOLOGY PROGRESS, Issue 3 2008Zhen Wang This paper reveals that a discontinuous in vitro induction, namely, the periodic presence and absence of foreign induction factors, might be, under a certain condition, more effective to stimulate stem cells' differentiation than a continuous induction. Bone marrow stem cells (BMSCs) derived from Sprague Dawley rats were employed to examine the effects of discontinuous additions of osteogenic supplements with a series of alternate frequency in contrast to those with continuous induction or no induction. The results demonstrated that a suitable discontinuous induction was more able to achieve osteogenesis than not only no induction but also the associated continuous induction. Additionally, the osteogenic supplements were confirmed to enhance cell differentiation but suppress cell proliferation. So, the combination of differentiation extent per cell and cell number accounts for the "unexpected" good osteogenic effect of the discontinuous induction. The induction effect was found to be dependent upon alternate frequency, and the optimum alternate period in our experimental systems was determined to be around 4 days. Since it is very common to change culture medium every 2,4 days, such a strategy of discontinuous induction does not bring any extra manual work but reduces the consumption of foreign induction factors and significantly enhances the global differentiation efficacy. Our work thus affords a convenient and practical approach to achieve differentiation of BMSCs, which might be useful for potential large-scale culture and differentiation of stem cells. Meanwhile, the existence of optimum frequency implies some unknown inherent rhythms of cell proliferation and differentiation. [source] The potential antioxidant effect of raloxifene treatment: a study on heart, liver and brain cortex of ovariectomized female ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2007Sibel Konyalioglu Abstract The antioxidant activity of some compounds buffer the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Recent studies documented that raloxifene has antioxidant properties in vitro. However, there are limited animal studies available to show raloxifene's antioxidant properties. We aimed to investigate the effects of raloxifene on antioxidant enzymes such as SOD, CAT and GPX, TrxR and the levels of GSH and MDA in heart, liver and brain cortex of ovariectomized female rats. Female Sprague Dawley rats weighing 300,350,g (n,=,24) were divided into three groups: (I) Eight non-ovariectomized rats were used as naive controls without any treatment (non-ovariectomized group, n,=,8). Five weeks after ovariectomy, (II) Ovariectomized placebo group (n,=,8) was given physiological saline, and (III) Raloxifene group (n,=,8) was given raloxifene 1,mg/kg,sc. daily for 12 days. Ovariectomy induced significant increases on SOD, GPX, CAT activity and MDA levels in brain, heart and liver tissues compared to non-ovariectomized rats (,p,<,0.05). Raloxifene treatment led to decreased levels of SOD activity in heart, GPX activity in brain and CAT activity in liver tissue when compared to ovariectomized group (,p,<,0.05) but there was no change in activity of TrxR in all groups. The levels of MDA in brain, heart and liver tissues increased in ovariectomized group when compared to non-overiectomized rats (,p,<,0.05). Raloxifene had a significant attenuating effect on the levels of MDA in brain and heart tissues. Our results also indicate that the levels of GSH in brain, heart and liver tissue decreased when compared to non-ovariectomized rats. Raloxifene treatment was observed to significantly increase the levels of GSH in brain and heart tissues (,p,<,0.05). However, there were insignificant differences for the GSH levels in liver tissues of ovariectomized placebo or raloxifene groups. In conclusion, our results demonstrate that raloxifene may be more effective against oxidative stress in heart and brain than in liver tissue. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effect of intravitreal injection of indocyanine green, triamcinolone acetonide and trypan blue on the electroretinographic response in the ratACTA OPHTHALMOLOGICA, Issue 2007C GARCHER CREUZOT Purpose: The purpose of this study was to evaluate the effects of intravitreal injection of ICG (indocyanine green), TB (trypan blue) and TA (triamcinolone acetonide) on the visual function assessed by electroretinogram (ERG) in the rat. Methods: Three groups of 12-week-old Sprague Dawley rats (n=6) received intravitreal injection in one eye of 0.1mL of either ICG 0.5mg/mL, TB 3mg/mL or TA 40mg/mL followed by a rinse with 1mL of saline solution. The controlateral eye was used as a control and was injected similarly with saline only. The scotopic ERG was recorded at different intensities (10mcds/m˛, 2500mcds/m˛ and 25000mcds/m˛) before injection and 28 days after treatment. Results: No effect of the treatment was observed on the ERG amplitudes and wave latencies in control eyes and in eyes treated with TB and TA. The ERG b-wave amplitudes and latencies were significantly reduced in eyes treated with ICG at 10mcds/m˛ and 2500mcds/m˛ but not at 25000mcds/m˛ (amplitude means: t0=174.8,V versus t28=55.0,V at 10mcds/m˛ p<0.05; t0=176.5,V versus t28=70.0,V at 2500mcds/m˛ p<0.05; t0=140.3,V versus t28=40.0,V at 25000mcds/m˛ p=0.057). The ERG a-wave amplitudes and latencies were also significantly lowered at 2500mcds/m˛ in eyes treated with ICG (amplitude means: t0=45.0,V versus t28=23,V p<0.05; latency means: t0=7.6msec versus t28=9.5msec p<0.01). Conclusions: This study shows a side effect of ICG on retinal function four weeks after a transient retinal exposure. TA and TB could be considered as interesting alternatives to ICG for macular surgery. [source] Effect of continuous infusion of asialoerythropoietin on short-term changes in infarct volume, penumbra apoptosis and behaviour following middle cerebral artery occlusion in ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2010Chrystal D Price Summary 1. Asialoerythropoietin (aEPO), a derivative of cytokine erythropoietin, has been shown to have neuroprotective effects without haematological complications when administered in single or repeated doses. The present study examines our hypothesis that aEPO may provide neuroprotection against programmed apoptotic cell death when administered in a continuous low dose. 2. Focal cerebral ischaemia was introduced by occlusion of the middle cerebral artery using a surgically placed intraluminal filament in young male Sprague Dawley rats (9 weeks old). After 90 min ischaemia, reperfusion was established by filament removal. Both study and control groups had implanted osmotic minipumps through which they received either aEPO (1 ,L/h; 20 ,g/kg per 24 h) or normal saline (1 ,L/h) for 4 days. On Day 4, infarct volume, the number of apoptotic cells and concentrations of activated caspase 3 and 9 were evaluated in the penumbra region. 3. Asialoerythropoietin was detected in the cerebrospinal fluid of the study group, whereas none was detected in the control group. Although there were no significant changes in haematocrit levels or behaviour scores (on Days 1 and 4) between the study and control groups, aEPO administration significantly reduced infarct volume in the study group compared with the control group (168 ± 19 vs 249 ± 28 mm3, respectively; P < 0.05). 4. The number of terminal deoxyribonucleotidyl transferase-mediated dUTP,digoxigenin nick end-labelling (TUNEL)-positive cells and the concentration of activated caspase 3 and 9 in the penumbra region were significantly lower in the study group compared with the control group. 5. In conclusion, our data suggest that aEPO provides a short-term, possibly histological, protection in young adult male rats when administered immediately after reperfusion. [source] | ||||||||||||||||