title: An apoE-derived mimic peptide, COG1410, alleviates early brain injury via reducing apoptosis and neuroinflammation in a mouse model of subarachnoid hemorrhage.
abstract: This study investigated the neuroprotective effects of COG1410, an apoliporotein E (apoE)-derived mimic peptide, against early brain injury (EBI) after subarachnoid hemorrhage (SAH). SAH was induced in C57BL/6J mice (n=68) by endovascular perforation. Mice received intravenous injection of COG1410 (2mg/kg) or equal volume of vehicle (saline). The mortality rate, neurological score, rotarod latencies, cell apoptosis, microglial activation, pro-inflammatory cytokines production and protein levels of apoptotic and inflammatory markers were assessed at 24h after sham operation or SAH. Results showed that COG1410 alleviated the neurological deficits associated with SAH. Compared with vehicle treatment group, the number of apoptotic cells and activated microglia decreased significantly in the COG1410 treated group. COG1410 enhanced Akt activation and suppressed caspase-3 cleavage. The imbalance of Bax and Bcl-2 induced by SAH was regulated by COG1410. Additionally, COG1410 attenuated cytokines production of IL-1β, IL-6 and TNF-α and suppressed the activation of JNK/c-Jun and NF-κB. Taken together, COG1410 protected against EBI via reducing apoptosis and neuroinflammation, through mechanisms that involve the regulation of apoptotic signaling and microglial activation. COG1410 is a potential neuroprotective agent for SAH treatment.
authors.affiliation: Departement of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Chongqing 400016, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Pang
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Cerebrovascular Disease, The Affiliated Hospital of Zunyi Medical College, Zunyi 563003, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.affiliation: Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.affiliation: Cognosci, Inc., Research Triangle Park, NC 27710, USA.
authors.forename: Fengqiao
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: jiangy0122@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Departement of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Chongqing 400016, China. Electronic address: sunxch1445@qq.com.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000517:prevention & control*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C524548:COG1410; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Apolipoprotein E; Apoptosis; Early brain injury; Neuroinflammation; Subarachnoid hemorrhage