title: Cyclosporin A ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway.
abstract: Nur77 is a potent pro-apoptotic member of the orphan nuclear receptor superfamily. It has been demonstrated that can mediate apoptosis in many system cells in response to extracellular stimuli. Our previous study revealed Nur77-mediated apoptotic also involved in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). CsA, a Nur77 inhibitor, can abolish DNA binding activity of Nur77, further inhibit the Nur77 dependent apoptosis pathway. CsA has the neuroprotective effects and has been demonstrated in ischemic stroke and traumatic brain injury. Hence, in this study was designed to explore the neuroprotective effects of CsA in EBI after SAH. Adult male SD rats were randomly assigned to four groups: (1) control group (n = 24); (2) SAH (n = 24); (3) SAH+DMSO group (n = 24); and (4) SAH+CsA (n = 24), 10 mg/kg of CsA or same volume of DMSO was administered by femoral vein injection at 15 min before SAH. CsA markedly decreased expressions of Nur77, p-Nur77, Bcl-2 and cyto C, and inhibited apoptosis.Improvement of neurological deficit, alleviation of brain edema and amelioration of EBI were obtained after prophylactic use of CsA. TUNEL-positive cells were reduced markedly in brain cortex by CsA. These findings suggest that neuroprotective effects of CsA during early peroid after SAH may be related to its inhibition of Nur77 dependent apoptosis pathway.
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province 210008, China.
authors: Yuxiang
authors: Y
authors: Dai
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province 210008, China.
authors: Qing
authors: Q
authors: Sun
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province 210008, China.
authors: Xing
authors: X
authors: Zhang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province 210008, China.
authors: Yangchun
authors: Y
authors: Hu
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province 210008, China.
authors: Mengliang
authors: M
authors: Zhou
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province 210008, China. Electronic address: shijixinnj@hotmail.com.
authors: Jixin
authors: J
authors: Shi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology; D053148:Caspase 3 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009460:Neurologic Examination; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000150:complications
chemical_list: D007166:Immunosuppressive Agents; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine; D053148:Caspase 3
keywords: Apoptosis; Arly brain injury; Cyclosporin A; Nur77; Subarachnoid hemorrhage