An apoE-derived mimic peptide, COG1410, alleviates early brain injury via reducing apoptosis and neuroinflammation in a mouse model of subarachnoid hemorrhage. (3rd August 2016)

• Record Type: Journal Article
• Authors: Wu, Yue; Pang, Jinwei; Peng, Jianhua; Cao, Fang; Vitek, Michael P.; Li, Fengqiao; Jiang, Yong; Sun, Xiaochuan
• Is Part Of: Neuroscience letters. Volume 627(2016)
• Page Start: 92
• Page End: 99
• Publication Date: 2016-08-03
• Subjects: Apolipoprotein E -- Subarachnoid hemorrhage -- Early brain injury -- Apoptosis -- Neuroinflammation; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.05.058
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: An apoE-derived peptide, COG1410, alleviated neurological deficits in SAH mice. Anti-apoptotic and anti-inflammatory effects of COG1410 contribute to the neuroprotective effect of COG1410. COG1410 regulates apoptotic and inflammatory signals, and suppresses microglial activation in the acute phase of SAH. 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/6 J mice (n = 68) by endovascular perforation. Mice received intravenous injection of COG1410 (2 mg/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 24 h 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.