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-in...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.展开更多
基金This work was partially supported by DOD contract CDMRP#W81XWH-16-C-0142.
文摘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.
