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Objective Using video tracking system to compare the effects of the locomotor activity between theophylline and caffeine in mice.Methods The KM mice were treated by theophylline and caffeine(both at 1,3,10,30,100 mg/kg)intraperitoneally respectively.After 10 min,the locomotor activity in the open field was recorded for 2 hours.The locomotor track,the total distance,the distances and distance ratio to total distance in central region were analyzed to evaluate the effects of these drugs on locomotor in mice.Results The mice administrated theophylline and caffeine both increased the total distances,and had similar bell-shaped dose-effect relationship.The distances reached the highest at 30 mg/kg theophylline((311±128)m)and 10 mg/kg caffeine ((279±89)m).The larger doses of caffeine inhibited the activity,and the total distance during 0～0.5 h was significantly decreased at the dose of 100 mg/kg(P＜0.05).Theophylline(30 and 100 mg/kg)and caffeine (30 mg/kg)significantly increased the distance ratio in central region(P＜0.01)and decreased the distance ratio in peripheral region(P＜0.01).Conclusion Theophylline and caffeine increase the total distance and the distance ratio in central region in mice,but have different valency and efficacy.
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Aim To determine whether pranlukast (ONO-1078), a cysteinyl leukotriene receptor antagonist, possesses therapeutic effect when administered after focal cerebral ischemia in mice. Methods Persistent focal cerebral ischemia was induced by middle cerebral artery occlusion. Pranlukast and edaravone, a positive control drug, were ip injected 1, 6 and 24 h after ischemia. The neurological deficits were evaluated by neurological scores and inclined plane test 24 and 48 h after the surgery. Forty-eight h later, the brain slices were prepared for measurements of infarct volume and the ratio of ischemic/non-ischemic hemispheres. Brain sections were cut and examined for neuron densities in different regions of the brain. The effects of pranlukast and edaravone were evaluated by the changes of these variables. Results Pranlukast (0.1 and 0.2 mg?kg -1) and edaravone (3 and 10 mg?kg -1) significantly reduced the neurological deficits, infarct volume (maximally 82.3%), ratio of ischemic/non-ischemic hemispheres, and attenuated the reduction of neuron densities in hippocampal CA1 region, cortex and striatum. Conclusion Pranlukast possesses therapeutic effect on ischemic insults when administered after ischemia as effective as edravone, indicating a therapeutic potential in the treatment of ischemic stroke.
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Phosphodiesterase(PDE) is hydrolase of 3',5'-cyclic adenosine monophosphate(cAMP) and 3',5'-cyclic guanosine monophosphate(cGMP).PDE3 are composed of two genes and distributed widely in vivo.Its inhibitors have been applied in antiplatelet aggregation and vasodilation.It has been reported that PDE3 inhibitors have neuroprotective effects on cerebral ischemia,which may provide new methods to prevention and therapy of cerebral ischemia.
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It has been proved that erythropoietin has neuroprotective effect and therapeutic action on cerebral ischemia in vivo and in vitro. The mechanisms of these actions may be involved in anti-exitotoxicity of aminoglutaric acid, regulating the synthesis of nitric oxide, antioxidation, antiinflammatory, inhibiting neuron apoptosis, accelerating angiogenesis, neurogenesis, neurotrophy and others. In addition, exogenous erythropoietin can enter brain tissue through blood-brain barrier and exert neuroprotection. So it is indicated that erythropoietin can be expected to be a new drug to prevent and treat cerebral ischemia.
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AIM:To confirm the action of the light transmission method in evaluating focal ischemic cerebral infarction on persistent focal cerebral ischemia in mice. METHODS:Persistent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Bederson's neurological scores, climbing board and hanging test were performed 24 h after ischemia, and infarct volume, brain hemisphere area, neuron density of cortex and subcortex were measured with computer-assisted imaging. Pranlukast ( 0.1 mg?kg -1) or nimodipine ( 0.4 mg?kg -1) were injected ip once daily for 3 days and to 1 h before MCAO assess the neuroprotective effect. RESULTS:The infarct volumes measured by light transmission closely correlated with that measured by TTC staining and neuron densities. The infarct volumes measured by light transmission well correlated with the neurological scores measured by integrated graded approach, too. Both pranlukast and nimodipine significantly attenuated infarct volumes and the ratio of ischemic/non-ischemic hemispheres, and reduced neurological deficits and neuron death. CONCLUSION:Light transmission and integrated graded approach can be used not only for qualitative analysis of focal cerebral ischemia, but also for evaluating the neuroprotective effect of drugs.