Ecdysterone protects gerbil brain from temporal global cerebral ischemia/reperfusion injury via preventing neuron apoptosis and deactivating astrocytes and microglia cells.
Ecdysterone (EDS), a common derivative of ecdysteroid, has shown its effects on alleviating cognitive impairment and improving the cognition and memory. However, the mechanisms remain unknown. Using temporal global forebrain ischemia and reperfusion-induced brain injury as a model system, we investigated the roles of EDS in improving cognitive impairment in gerbil. Our results demonstrated that intraperitoneal injection of EDS obviously increased the number of surviving neuron cells by Nissl and neuronal nuclei (NeuN) staining. Indeed, the protecting effects of EDS are because of its ability to prevent the apoptosis of neuron cells as evidenced by TUNEL staining and caspase-3 deactivation in the brain of temporal global forebrain ischemia/reperfusion-treated gerbil. Moreover, EDS administration suppressed the ischemia stimulated activity of astrocytes and microglia cells by inhibiting the production of tumor necrosis alpha (TNF-α) in the brain of gerbil. More importantly, these actions of neurons and astrocytes/microglia cells in response to EDS treatment played pivotal roles in ameliorating the cognitive impairment in the ischemia/reperfusion-injured gerbil. In view of these observations, we not only decipher the mechanisms of EDS in reducing the syndrome of ischemia, but also provide novel perspectives to combat ischemic stroke.
Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.
Wei
W
Wang
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
Tao
T
Wang
Department of Pharmacy, People's Hospital, Peking University, Beijing 100044, PR China.
Wan-Yu
WY
Feng
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
Zhan-You
ZY
Wang
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Mao-Sheng
MS
Cheng
Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China. Electronic address: neurosurgeonwangyj@hotmail.com.
Yun-Jie
YJ
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D004441:Ecdysterone / Q000494:pharmacology / Q000627:therapeutic use*; D005849:Gerbillinae; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D004441:Ecdysterone; D053148:Caspase 3
Caspase-3; Ecdysterone; Gerbil; Ischemia; Reperfusion; Tumor necrosis factor α