1. Apolipoprotein E mimetic peptide CN-105 improves outcome in a murine model of SAH
- Author
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Yanli Tan, Ji Liu, Guanen Zhou, Haichen Wang, Daniel T. Laskowitz, Chuan Fang, and Bradley J. Kolls
- Subjects
0301 basic medicine ,Apolipoprotein E ,Male ,Subarachnoid hemorrhage ,Traumatic brain injury ,subarachnoid hemorrhage ,Central nervous system ,Inflammation ,Microgliosis ,Neuroprotection ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Vasospasm, Intracranial ,microgliosis ,cardiovascular diseases ,Gliosis ,vasospasm ,apolipoprotein E ,Neurons ,business.industry ,Brain ,Vasospasm ,Cerebral Arteries ,medicine.disease ,nervous system diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Neuroprotective Agents ,Vasoconstriction ,inflammation ,Anesthesia ,Nerve Degeneration ,Encephalitis ,Original Article ,Neurology (clinical) ,Microglia ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Oligopeptides ,030217 neurology & neurosurgery - Abstract
ObjectiveSubarachnoid haemorrhage (SAH) accounts for 3% of all strokes, and is associated with significant morbidity and mortality. There is growing evidence implicating apolipoprotein E (apoE) in mediating adaptive anti-inflammatory and neuroprotective responses following ischaemic and traumatic brain injury. In the current study, we test the efficacy of a small apoE mimetic peptide, CN-105 in a murine model of SAH.MethodsMice subjected to SAH received repeated intravenous injections of CN-105 every 12 hours for 3 days, with the first dose given 2 hours after injury. Daily functional outcomes were assessed by rotarod and neurological severity score. Haemorrhage grade and cerebral vascular diameters were measured at 5 days post-SAH. Cerebral microgliosis, neuronal degeneration and survival were analysed at 5 and 35 days post-SAH, respectively.ResultsCN-105 reduces histological evidence of inflammation, reduces vasospasm and neuronal injury and is associated with improved long-term behavioural outcomes in a murine model of SAH.ConclusionsGiven its favourable pharmacokinetic profile, central nervous system penetration and demonstration of clinical safety, CN-105 represents an attractive therapeutic candidate for treatment of brain injury associated with SAH.
- Published
- 2018