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An apoE-derived mimic peptide, COG1410, alleviates early brain injury via reducing apoptosis and neuroinflammation in a mouse model of subarachnoid hemorrhage.
- Source :
-
Neuroscience letters [Neurosci Lett] 2016 Aug 03; Vol. 627, pp. 92-9. Date of Electronic Publication: 2016 May 27. - Publication Year :
- 2016
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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.<br /> (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Cerebral Cortex drug effects
Cerebral Cortex metabolism
Cerebral Cortex pathology
Disease Models, Animal
Encephalitis etiology
Encephalitis metabolism
Interleukin-1beta metabolism
Interleukin-6 metabolism
Male
Mice
Mice, Inbred C57BL
Microglia drug effects
Microglia physiology
Subarachnoid Hemorrhage complications
Survival Analysis
Tumor Necrosis Factor-alpha metabolism
Apolipoproteins E administration & dosage
Apoptosis drug effects
Encephalitis prevention & control
Neuroprotective Agents administration & dosage
Subarachnoid Hemorrhage prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7972
- Volume :
- 627
- Database :
- MEDLINE
- Journal :
- Neuroscience letters
- Publication Type :
- Academic Journal
- Accession number :
- 27241720
- Full Text :
- https://doi.org/10.1016/j.neulet.2016.05.058