RT Journal Article
SR Electronic
T1 Apolipoprotein E mimetic peptide CN-105 improves outcome in a murine model of SAH
JF Stroke and Vascular Neurology
FD BMJ Publishing Group Ltd
SP 222
OP 230
DO 10.1136/svn-2018-000152
VO 3
IS 4
A1 Liu, Ji
A1 Zhou, Guanen
A1 Kolls, Bradley J
A1 Tan, Yanli
A1 Fang, Chuan
A1 Wang, Haichen
A1 Laskowitz, Daniel T
YR 2018
UL http://svn.bmj.com/content/3/4/222.abstract
AB Objective Subarachnoid 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.Methods Mice 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.Results CN-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.Conclusions Given 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.