title: Levetiracetam Prevents Perforin Mediated Neuronal Injury Induced by Acute Cerebral Ischemia Reperfusion.
abstract: The purpose of this study is to explore the neuroprotection mechanism of levetiracetam (LEV) with acute focal cerebral ischemia-reperfusion (I/P) mouse. The cerebral artery I/P animal model was prepared with a middle artery cerebral occlusion method. For drug intervention, mice were intraperitoneally injected with LEV with a dose of either 15 or 150 mg/kg. Neuronal injury was evaluated by measuring the infarct area, apoptosis ratio, and observation of blood-brain barrier ultrastructure with transmission electron microscope. CD8(+) antibody and perforin antibody were used to make cross-reference screen through flow cytometry to determine a perforin-positive rate in CD8(+) T lymphocytes (PFN + %). Injection of LEV can reduce infarct area, apoptosis ratio, and blood-brain barrier damage 24 h later after acute I/P in WT mice. In vitro, perforin can lower hippocampal neuron viability. In vivo, removing perforin can relieve neuronal injury. High dose injection of LEV (150 mg/kg) can inhibit perforin secreting from CD8(+)T lymphocytes. In addition, LEV can still protect neurons with perforin knockout mice. Therefore, our results suggested that LEV may contribute to neuron protection after cerebral ischemia reperfusion. The possible mechanism may be related with perforin release. However, we cannot roll out other mechanisms.
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Bao
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China.
authors.forename: Xiahong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, 200032, Shanghai, China. 2853128976@qq.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, East Hospital, Tongji University School of Medicine, 150Jimo Road, Shanghai, 200120, China. ligang@tongji.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology*; D005260:Female; D000077287:Levetiracetam; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D054353:Perforin / Q000378:metabolism*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D054353:Perforin; D000077287:Levetiracetam; D010889:Piracetam
keywords: CD8+T lymphocytes; Cerebral ischemia-reperfusion; LEV; Neuroprotection; Perforin