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      Atorvastatin attenuates cognitive deficits through Akt1/caspase-3 signaling pathway in ischemic stroke.

      1 , 1 , 1 , 2

      Brain research

      Elsevier BV

      Akt1, Atorvastatin, Caspase-3, Cerebral ischemia

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          Abstract

          Neuronal damage in the hippocampal formation is more sensitive to ischemic stimulation and easily injured, causing severe learning and memory impairment. Therefore, protection of hippocampal neuronal damage is the main contributor for learning and memory impairment during cerebral ischemia. Atorvastatin has been reported to ameliorate ischemic brain damage after ischemia reperfusion (I/R). However, its molecular mechanism has not been elucidated clearly. In this study, we established four-vessel occlusion model in rats with cerebral ischemia. Here, we demonstrated that atorvastatin significantly improves the behavior of I/R-rat in open field tasks. We also found that atorvastatin significantly shortens the distance and time of loading onto the hidden platform in the positioning navigation process, decreases the latency in the space exploration process when cognitive testing with Morris water maze was performed during ischemic stroke in rats. Furthermore, the survival rate of neurons in the CA1 area of the hippocampus and the phosphorylation of Akt (Ser473) in the neurons are increased, whereas the expression of caspase-3 are inhibited by atorvastatin. However, after an intracerebroventricular injection of LY294002 (an inhibitor of Akt1), the above neuroprotective effects of atorvastatin are attenuated. In summary, our results imply atorvastatin may improve the survival rate of hippocampal neurons and reduce the impairment of learning and memory by downregulating the activation of the caspase-3 via increasing the phosphorylation of Akt1 during ischemia/reperfusion.

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          Author and article information

          Journal
          Brain Res.
          Brain research
          Elsevier BV
          1872-6240
          0006-8993
          Dec 10 2015
          : 1629
          Affiliations
          [1 ] The Third Hospital of Hebei Medical University, PR China.
          [2 ] The Third Hospital of Hebei Medical University, PR China. Electronic address: biowangxianying@126.com.
          Article
          S0006-8993(15)00794-5
          10.1016/j.brainres.2015.10.032
          26597376

          Cerebral ischemia, Atorvastatin, Akt1, Caspase-3

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