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Male Sprague Dawley Rats (male + sprague_dawley_rat)
Selected AbstractsSmoke 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] | |||||||||||||