Concerns about rodent models for aging research.
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Aging↗
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The effects of twisted ischaemic adnexa managed by detorsion on ovarian viability and histology: an ischaemia-reperfusion rodent model.
This prospective controlled follow-up study was designed to examine the effects of adnexal torsion on long-term ovarian histology and radical scavenger (FRS) activity, and subsequent viability following the detorsion of twisted ischaemic adnexa, in a primate centre of a university clinic. Adnexal torsion/occlusion was created by twisting the adnexa three times and fixing on to the side wall or by applying vascular clips in cycling female rats at 70 days of age. Following an ischaemic period of 4 to 36 h, the twisted adnexas were surgically removed and fixed. In the second group of rats, following the above ischaemic periods, the torsion/occlusion were relieved by detwisting or removing the vascular clips. Then the animals were reperfused for a week and adnexas were extirpated. After both ischaemia and reperfusion, the removed adnexas were examined histologically and tissue concentrations of glutathione peroxidase, superoxide dismutase, catalase and glutathione were determined. Regardless of the ischaemia time, all the twisted adnexas were black-bluish in appearance. Despite the gross ischaemic-haemorrhagic features, histological sections revealed negligible changes, with intact ovarian structure similar to controls in 4-24 h groups. Though decreased compared with controls, the change in tissue concentrations of FRS was not significant in 4-24 h groups. Only the 36 h group showed prominent congestion on all sections and a significant decrease in all radical scavenger concentrations studied. While no long-term reperfusion injury was observed histologically in 4-24 h groups, the 36 h group ended with adnexal necrosis. Our findings support the importance of early diagnosis and conservative surgical management (detorsion) in adnexal torsion. Lack of histological changes and unimpaired FRS metabolism are consistent with the recent data that vascular compromise is caused by venous or lymphatic stasis in early torsion and that adnexal integrity is not correlated with gross ischaemic appearance, thus providing evidence of adnexal resistance against ischaemia.
Adnexa Uteri↗
Role and Regulation of Chemokines in Rodent Models of Lung Inflammation.
Acute inflammatory lung injury has been induced in rats by intrapulmonary deposition of immunoglobulin G immune complexes or instillation of bacterial lipopolysaccaride. Several juxtaposed cysteine residue (CXC) chemokines (e.g., macrophage inflammatory protein 2 [MIP-2] and cytokine-induced neutrophil chemoattractant [CINC]) and CC chemokines (MIP-1alpha, MIP-1Beta, and monocyte chemoattractant protein-1 [MCP-1]) are upregulated in these acute injury models and appear in substantial amounts in bronchoalveolar (BAL) fluids during the inflammatory response. Antibody-induced blockade of either tumor necrosis factor alpha (TNFalpha ) or the complement activation product C5a results in significant reductions in BAL levels of chemokines, causing depressed inflammatory responses and diminished lung injury. These data suggest that both TNFalpha (a product of activated macrophages) and C5a participate as positive feedback mediators, resulting in maximal expression of chemokines. These chemokines are involved in recruitment of neutrophils and activation of tissue macrophages, the collective products of which cause acute lung injury mediated by the generation of oxidants and release of proteases.
Journal Article↗
Salicylate potentiates amikacin therapy in rodent models of Klebsiella pneumoniae infection.
In vitro effects of salicylate on Klebsiella pneumoniae include capsule repression and enhanced aminoglycoside activity. The effects of high-dose salicylate on amikacin therapy were assessed in animal models. In a mouse lethality model, amikacin protective doses were reduced up to 12-fold by salicylate doses of 277 mg/kg. Salicylate alone increased the LD50 for K. pneumoniae in mice by nearly 1 log unit. In a lobar pneumonia model, rats received salicylate-amikacin intravenously 3 days after challenge, and bacteria were quantified from lung tissue on day 7. Rats receiving one-fourth the minimum effective amikacin dose had 1 x 10(6) cfu/g of lung, while no bacteria were detected in those also receiving salicylate (173 mg/kg). At one-eighth the minimum effective dose of amikacin, salicylate prevented the development of pneumonia. Salicylate potentiation of antimicrobial therapy far surpassed that observed in vitro, yet the potentiation was abolished in neutropenic animals. Thus, salicylate may enhance phagocytosis rather than antibiotic action in therapy.
Amikacin↗
Topical prophylaxis for Lyme disease after tick bite in a rodent model.
To determine whether infection with the Lyme disease spirochete (Borrelia burgdorferi) can be aborted by topical application of antibiotic to the site of tick attachment, individual infected nymphal deer ticks (Ixodes dammini) were permitted to feed on the ears of mice, and various antibiotics were applied to the feeding site at intervals after the replete infecting tick had detached. Infection in each mouse was determined by serology and by xenodiagnosis at 4 weeks after the bite of the infected tick. None of these mice became infected when antibiotic was topically applied to the site of tick attachment within 2 days after the spirochete-infected ticks had detached. In contrast, all nontreated and virtually all solvent-treated mice became persistently infected. Thus, persistent infection by the agent of Lyme disease can be aborted by appropriate topical application of antibiotic.
Administration, Topical↗
Protective effects of an N-terminal fragment of bactericidal/permeability-increasing protein in rodent models of gram-negative sepsis: role of bactericidal properties.
Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) on bacterial infections were determined. Intravenous (i.v.) rBPI21 increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria. rBPI21 inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI21 increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI21 alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI21 is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI21 in models of gram-negative infection.
Animals↗
Re: initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models.
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Animals↗
RESPONSE: re: initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models
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Journal Article↗
Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes.
Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC beta inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration and albuminuria, but also overexpression of glomerular mRNA for transforming growth factor beta1 (TGF-beta1) and extracellular matrix (ECM) proteins in streptozotocin-induced diabetic rats, a model for type 1 diabetes. In this study, we examined the long-term effects of a PKC beta inhibitor on glomerular histology as well as on biochemical and functional abnormalities in glomeruli of db/db mice, a model for type 2 diabetes. Administration of a PKC beta inhibitor reduced urinary albumin excretion rates and inhibited glomerular PKC activation in diabetic db/db mice. Administration of a PKC beta inhibitor also prevented the mesangial expansion observed in diabetic db/db mice, possibly through attenuation of glomerular expression of TGF-beta and ECM proteins such as fibronectin and type IV collagen. These findings provide the first in vivo evidence that the long-term inhibition of PKC activation in the renal glomeruli can ameliorate glomerular pathologies in diabetic state, and thus suggest that a PKC beta inhibitor might be an useful therapeutic strategy for the treatment of diabetic nephropathy.
Albuminuria↗
Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people in industrialized countries. Although various anti-inflammatory and antiapoptotic modalities have shown neuroprotective effects in experimental models of TBI, to date, no specific pharmacological agent aimed at blocking the progression of secondary brain damage has been approved for clinical use. Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally been viewed as a hematopoiesis-regulating hormone. The newly discovered neuroprotective properties of Epo lead us to investigate its effect in TBI in a mouse model of closed head injury. Recombinant human erythropoietin (rhEpo) was injected at 1 and 24 h after TBI, and the effect on recovery of motor and cognitive functions, tissue inflammation, axonal degeneration, and apoptosis was evaluated up to 14 days. Motor deficits were lower, cognitive function was restored faster, and less apoptotic neurons and caspase-3 expression were found in rhEpo-treated as compared with vehicle-treated animals (P<0.05). Axons at the trauma area in rhEpo-treated mice were relatively well preserved compared with controls (shown by their density; P<0.01). Immunohistochemical analysis revealed a reduced activation of glial cells by staining for GFAP and complement receptor type 3 (CD11b/CD18) in the injured hemisphere of Epo- vs. vehicle-treated animals. We propose that further studies on Epo in TBI should be conducted in order to consider it as a novel therapy for TBI.
Animals↗
Gastric distention exacerbates ischemia in a rodent model of partial gastric devascularization.
Occult ischemia of the mobilized gastric fundus is an important etiologic factor for esophagogastric anastomotic leaks after esophagectomy. Postoperative gastric distention is another possible predisposing factor for anastomotic leakage. We hypothesized that gastric distention could worsen gastric ischemia. To test this hypothesis, gastric tissue perfusion was studied in 20 Sprague-Dawley rats. Baseline serosal gastric tissue perfusion was measured by laser-Doppler flowmetry at a point 10 mm distal to the gastroesophageal junction. Perfusion was measured after left gastric artery occlusion, gastric distention to 20 cm water pressure, and combined left gastric artery occlusion and gastric distention. Gastric tissue perfusion (in tissue perfusion units, TPU) was 64.2 +/- 9.1 TPU at baseline measurement, 18.6 +/- 4.3 TPU after left gastric artery occlusion, 22.0 +/- 4.1 TPU after gastric distention, and 7.8 +/- 1.8 TPU after combined left gastric artery occlusion and gastric distention. Distention (P < 0.0001) and arterial occlusion (P < 0.0001) both reduced gastric tissue perfusion; of the two, arterial occlusion produced the greatest reduction in perfusion (P < 0.021). The combination of distention and arterial occlusion caused greater reduction in gastric perfusion than either factor alone (P < 0.0001). In this model, gastric distention exacerbated the ischemia produced by partial gastric devascularization. In clinical esophageal surgery, postoperative gastric distention may similarly potentiate the ischemic effects of gastric transposition for esophageal reconstruction.
Anastomosis, Surgical↗
Differential spinal cord gene expression in rodent models of radicular and neuropathic pain.
BACKGROUND: Neuropathic pain and radicular low back pain both have a major impact on human health worldwide. Microarray gene analysis on central nervous system tissues holds great promise for discovering novel targets for persistent pain modulation. METHODS: Rat models of lumbar radiculopathy (L5 nerve root ligation) and neuropathy (L5 spinal nerve transection) were used for these studies. The authors measured mechanical allodynia followed by analysis of global gene expression in the lumbar spinal cord at two time points (7 days and 14 days) after surgery using the Affymetrix RAE230A GeneChip(R) (Santa Clara, CA). The expression patterns of several genes of interest were subsequently confirmed using real-time reverse transcriptase polymerase chain reaction. RESULTS: The authors observed similarly robust mechanical allodynia in both models. Second, they observed significant differences in lumbar spinal cord gene expression across chronic pain models. There was little overlap between genes altered in each injury model, suggesting that the site and type of injury produce distinct spinal mechanisms mediating the observed mechanical allodynia. The authors further confirmed a subset of the genes using reverse transcriptase polymerase chain reaction and identified several genes as either neuropathy-associated genes or radiculopathy-associated genes. CONCLUSIONS: These two models of persistent pain produce similar allodynic outcomes but produce differential gene expression. These results suggest that diverging mechanisms lead to a common behavioral outcome in these pain models. Furthermore, these distinct pathophysiologic mechanisms in neuropathic versus radicular pain may implicate unique drug therapies for these types of chronic pain syndromes.
Animals↗
Neuroprotection by encapsulated choroid plexus in a rodent model of Huntington's disease.
Choroid plexus from neonatal pigs was encapsulated in alginate microcapsules and transplanted into the rat striatum. Three days later, the same animals received unilateral injections of quinolinic acid (225 nmol) into the ipsilateral striatum. Choroid plexus transplants ameliorated the weight loss and motor impairments resulting from QA. Histological analysis demonstrated that choroid plexus transplants reduced the volume of striatal damage and protected ChAT-, but not NADPH-diaphorase-positive neurons. These data are the first to demonstrate that transplanted choroid plexus cells can protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington's disease.
Alginates↗
Membrane-permeable radical scavenger, tempol, reduces multiple organ injury in a rodent model of gram-positive shock.
OBJECTIVE: An enhanced formation of reactive oxygen species contributes to the multiple organ dysfunction syndrome (MODS) caused by endotoxin. We have recently discovered that two cell wall components, namely lipoteichoic acid (LTA) and peptidoglycan (PepG) of the gram-positive bacterium, Staphylococcus aureus, synergize to cause shock and MODS in the rat. Here, we investigate the effects of a membrane-permeable radical scavenger (tempol) on the circulatory failure and MODS (kidney, liver, lung) caused by coadministration of LTA (3 mg/kg i.v.) and PepG (10 mg/kg i.v.) in the anesthetized rat. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: Thirty-four anesthetized, male Wistar rats. INTERVENTIONS: After surgical preparation, anesthetized rats were observed for 6 hrs. Control rats were given vehicle (control plus saline, 2 mL/kg bolus injection, followed by an infusion of 1.5 mL/kg i.v., n = 6) or tempol (control plus tempol, 100 mg/kg i.v. bolus injection, followed by an infusion of 30 mg/kg i.v., n = 6). Gram-positive septic shock was induced by coadministration of LTA (3 mg/kg i.v.) and PepG (10 mg/kg i.v.) (LTA/PepG plus saline, n = 12). Another group of rats was pretreated with tempol before shock was induced (LTA/PepG plus tempol, 100 mg/kg i.v. bolus injection, 15 mins before LTA/PepG administration, followed by an infusion of 30 mg/kg i.v., n = 10). MEASUREMENTS AND MAIN RESULTS: Within 6 hrs, administration of LTA/PepG resulted in hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury, and increased plasma concentrations of nitrite/nitrate. Pretreatment of rats with tempol augmented the hypotension but attenuated the renal dysfunction and the hepatocellular injury/dysfunction caused by LTA/PepG. Tempol did not affect the increase in nitrite/nitrate caused by LTA/PepG. CONCLUSIONS: These results imply that an enhanced formation of reactive oxygen species (including superoxide anions) contributes to the kidney and liver injury and dysfunction caused by LTA/PepG in the anesthetized rat.
Animals↗
The selective guanylate cyclase inhibitor ODQ reduces multiple organ injury in rodent models of Gram-positive and Gram-negative shock.
OBJECTIVE: An enhanced formation of endogenous nitric oxide contributes to the circulatory failure caused by endotoxin (lipopolysaccharide). Many of the biological actions of nitric oxide are mediated by the guanylate cyclase/cyclic guanosine 3prime;,5'-monophosphate system. We recently discovered that two cell wall components, namely lipoteichoic acid and peptidoglycan of the Gram-positive bacterium Staphylococcus aureus, synergize to cause shock and multiple organ dysfunction syndrome in the rat. Here we investigate the effects of a selective guanylate cyclase inhibitor, 1H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ), on the circulatory failure and multiple organ dysfunction syndrome (kidney, liver, lung) caused by a) coadministration of lipoteichoic acid and peptidoglycan (Gram-positive shock) or b) lipopolysaccharide (Gram-negative shock) in the anesthetized rat. Furthermore, we investigated whether ODQ scavenges superoxide anions and/or hydroxyl radicals. DESIGN: The in vivo portion of the study was a prospective, randomized, controlled animal study. The in vitro portion included a) cultured ventricular myoblasts of the rat, H9c2(2-1) cells, and b) a cell free superoxide anion assay system. SETTING: University-based research laboratory. SUBJECTS: Seventy-five anesthetized, male Wistar rats were used for the in vivo study. INTERVENTIONS: For the in vivo portion of the study, after surgical preparation, anesthetized rats were observed for 6 hrs. All rats were pretreated and received an intravenous infusion of saline (1.5 mL.kg-1.hr-1), which was maintained throughout the experiment. The rats were assigned to nine groups. Group 1 contained control rats (sham) subjected to 2 mL/kg saline intraperitoneally, 2 hrs before the experiment (n = 7). Group 2 contained control rats (sham) that received 2 mg/kg ODQ intraperitoneally, 2 hrs before the experiment (n = 9). Group 3 contained control rats (sham) that received 2 mL/kg dimethyl sulfoxide, 30% v/v in saline intraperitoneally, as a vehicle for ODQ, 2 hrs before the experiment (n = 6). In group 4 rats, Gram-positive shock was induced by coadministration of lipoteichoic acid (3 mg/kg intravenously) and peptidoglycan (10 mg/kg intravenously) (n = 10). In group 5, rats were pretreated with ODQ (as described previously) before lipoteichoic acid/peptidoglycan (n = 9). In group 6, rats were pretreated with dimethyl sulfoxide (as described previously) before lipoteichoic acid/peptidoglycan (n = 7). In group 7, Gram-negative shock was induced by lipopolysaccharide (6 mg/kg intravenously) (n = 11). In group 8, rats were pretreated with ODQ (as described previously) before lipopolysaccharide (n = 8). In group 9, rats were pretreated with dimethyl sulfoxide (as described previously) before lipopolysaccharide (n = 8). For the in vitro portion of the study, rat cells were preincubated with vehicle (saline and/or dimethyl sulfoxide) and ODQ (0.1 microM to 1 mM) for 2 hrs. The cells then were exposed to H2O2 (1 mM) for 4 hrs at 37 degrees C, after which time cell viability was determined by measuring the mitochondrial-dependent reduction of 3-(4,5-di-methyliazol-2-yl)-2,5-diphenyltetrazolium bromide to blue formazan. Next, an aqueous solution was incubated with ODQ (as described previously), and superoxide anions were produced by using a hypoxanthine/xanthine-oxidase assay. The chemiluminescence assay was used to evaluate any potential antioxidative effects of ODQ. MEASUREMENTS AND MAIN RESULTS: In vivo, administration of lipoteichoic acid/peptidoglycan or lipopolysaccharide resulted within 6 hrs in hypotension, acute renal dysfunction, hepatocellular injury, and lung injury. Pretreatment of rats with ODQ attenuated the renal dysfunction, lung injury, and hepatocellular injury caused by lipoteichoic acid/peptidoglycan or lipopolysaccharide. In vitro, administration of H2O2 (for 4 hrs) to rat cardiomyoblasts decreased mitochondrial respiration attributable to generation of hydroxyl radicals. Pretreatment of cells with ODQ did not abolish this cell injury. In addition, ODQ did not scavenge superoxide anions. CONCLUSIONS: These results imply that ODQ, an inhibitor of guanylate cyclase, reduces the multiple organ injury and dysfunction caused by wall fragments of Gram-positive or Gram-negative bacteria in the anesthetized rat. The observed protective effects of ODQ are not attributable to the ability of ODQ to reduce the formation or the effects of superoxide anions or hydroxyl radicals.
Animals↗
Effects of Gd-DTPA after osmotic BBB disruption in a rodent model: toxicity and MR findings.
OBJECTIVE: This experiment was done to evaluate the gross neurotoxicity of intravenous Gd-DTPA administered in conjunction with osmotic blood-brain barrier (BBB) disruption and to image a human small cell lung carcinoma intracerebral tumor xenograft before and after osmotic BBB disruption. MATERIALS AND METHODS: Neurotoxicity studies were performed in normal Sprague-Dawley rats following osmotic BBB disruption by the injection of 25% mannitol in the right internal carotid artery and intravenous administration of Gd-DTPA (n = 10). Animals were observed for major neurologic changes such as seizure or substantial motor defects, and after death neuropathologic examination was performed. Human small cell lung carcinoma cells were implanted intracerebrally in athymic nude rats (n = 4). Gadopentetate dimeglumine was injected intravenously and serial T1-weighted images were obtained. Blood-brain barrier disruption was produced in each animal, followed by a second dose of intravenous Gd-DTPA, and imaging studies were repeated. RESULTS: No gross neurologic toxicity was observed. Tumors showed dense enhancement in a small area, and BBB disruption resulted in marked enhancement in most of the gray matter of the right cerebral hemisphere. CONCLUSION: Gadopentetate dimeglumine appears to be safe in doses up to 21 mmol/m2 in conjunction with barrier disruption in rats. A human small cell lung carcinoma intracerebral xenograft provides a useful method to study brain tumors.
Animals↗
Improving drug delivery to intracerebral tumor and surrounding brain in a rodent model: a comparison of osmotic versus bradykinin modification of the blood-brain and/or blood-tumor barriers.
OBJECTIVE: To compare transient blood-brain barrier disruption (BBBD) by hypertonic mannitol with pharmacological modification of the blood-tumor barrier by the vasoactive peptide bradykinin for delivery of small and large agents to nude rat intracerebral xenografts. METHODS: Female nude rats (n = 104) with 6-day intracerebral human small cell lung carcinoma tumors were treated using BBBD (n = 24), intracarotid bradykinin (n = 38), or saline (controls, n = 32) administered intra-arterially. During or immediately after infusion, the rats were given radiolabeled agent (methotrexate or dextran 70; Dupont NEN, Boston, MA). The rats were killed 10 minutes later, and samples of tumor and brain regions were obtained for scintillation counting. Twenty-two additional rats were examined using magnetic resonance imaging after administering one of two contrast agents (gadoteridol or iron oxide nanoparticles) or saline (controls) in conjunction with BBBD or bradykinin. RESULTS: After BBBD, the delivery of both small (methotrexate) and large (dextran 70) radiolabeled tracers was increased 2- to 6-fold in the tumor and 3- to 20-fold in surrounding brain, as compared with saline controls. After bradykinin treatment, there was minimal change in delivery of methotrexate or dextran 70 to tumor and brain around tumor, with the greatest increase less than 60% over controls. Magnetic resonance imaging demonstrated increased delivery of both small and large contrast agents to the treated hemisphere after BBBD. In comparison, no increased tumor enhancement could be detected after bradykinin treatment. CONCLUSION: BBBD resulted in global delivery of a variety of agents in a wide range of sizes. In this human brain tumor xenograft model, bradykinin was not effective at increasing delivery to the tumor of any agent tested.
Animals↗
The effect of groups II and III metabotropic glutamate receptor activation on neuronal injury in a rodent model of traumatic brain injury.
OBJECTIVE: The role of metabotropic glutamate receptor activation after traumatic brain injury (TBI) is not well understood. In vitro studies suggest that activation of Groups II and III metabotropic glutamate receptors may provide some degree of neuroprotection and may be potential targets for the development of therapeutic strategies. Thus, we examined the effects of Group II and Group III selective agonists on neuronal degeneration after in vivo TBI. METHODS: Fifty male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury immediately followed by an intracranial injection of 2-(2',3')-dicarboxycyclopropylglycine (DCG-IV) (Group II) or (R,S)-4-phosphonophenylglycine (Group III) in the CA2 and CA3 areas of the hippocampus. DCG-IV was injected at doses of 20 fmol, 100 fmol, and 500 fmol, and (R,S)-4-phosphonophenylglycine was injected at 8 nmol, 40 nmol, and 200 nmol. Vehicle injection control groups were used for comparison with each drug group. All animals were killed 24 hours after TBI was induced. Four 50-microm brain sections were obtained from each animal and stained for degenerating neurons with the fluorochrome Fluoro-Jade. Two independent, blinded investigators counted the number of degenerating (Fluoro-Jade-positive) neurons in the CA2 and CA3 areas of the hippocampus of each brain section. RESULTS: Compared with vehicle, the 500-fmol dose of DCG-IV significantly reduced the number of Fluoro-Jade-positive degenerating neurons (P < 0.001). Lower doses of DCG-IV were associated with a decreased but not statistically significant number of Fluoro-Jade-positive neurons. In contrast, (R,S)-4-phosphonophenylglycine had no significant effect on the number of degenerating neurons. CONCLUSION: Administration of selective Group II metabotropic glutamate receptor agonists protects neurons against in vivo TBI. These receptors may thus be a promising target for future neuroprotective drugs.
Animals↗