医学
长时程增强
缺血
海马结构
麻醉
神经保护
突触可塑性
海马体
兴奋剂
神经科学
芬戈莫德
记忆障碍
神经可塑性
药理学
内科学
心理学
认知
受体
多发性硬化
精神科
作者
Maryam Nazari,Somaye Keshavarz,Ali Rafati,Mohammad Reza Namavar,Masoud Haghani
标识
DOI:10.1016/j.brainresbull.2016.04.004
摘要
Fingolimod (FTY720) is a known sphingosine-1-phosphate (S1P) receptor agonist. Several studies have shown the therapeutic efficacy of FTY720 in neurodegenerative disorders. However, the neuroprotective mechanisms in brain ischemia have not been adequately studied. Therefore, the present study aimed to investigate the effects of FTY720 on the impairment of learning and memory and hippocampal synaptic plasticity induced by middle cerebral artery occlusion (MCAO) in ischemic brain injury. Twenty eight male rats were randomly divided into four groups of control (n = 7), sham (n = 8), ischemic-reperfusion + vehicle (I/R + V; n = 7), and I/R + FTY720 (n = 6). After 1 h of the occlusion of artery, the filament was gently withdrawn to allow reperfusion for the next 7 days. The animals first received a dose of FTY720 (0.5 mg/Kg) or its vehicle (intra-peritoneal) twenty-four hours before surgery in I/R + FTY720 and I/R + V groups, respectively. The administration of FTY720 or its vehicle continued every other day. The passive avoidance test and field potential recording were used for evaluation of learning, memory and synaptic plasticity. The brain infarct volume was measured by triphenyltetrazolim hydrochloride (TTC) staining. MCAO caused infarct damage in the rat’s brain tissue. The administration of FTY720 significantly reduced the size of the lesion, improved the memory impairment of MCAO rats, and increased the STL time. In addition, the field potential recording demonstrated a marked reduction in induction of long-term potentiation of MCAO animals. However, administration of FTY720 recovers the magnitude of the LTP without any effects on presynaptic plasticity and neurotransmitter release probability. The results of this study demonstrated that MCAO in rats impairs the retention of passive avoidance tasks and multiple injection of FTY720 improved the memory performance after MCAO by LTP induction via post-synaptic mechanisms.
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