Over 325,000 people die from cardiac arrest each year. Prognosis is poor and survivors typically experience persistent neurologic deficits. Currently, neuroprotective treatments to reduce brain injury in cardiac arrest survivors are limited and ineffective. This study evaluates the potential neuroprotection induced by intranasal insulin in a rodent model of asphyxial cardiac arrest. Male Long Evans rats were subjected to eight minutes of asphyxial cardiac arrest followed by cardiopulmonary resuscitation (CPR). Rats were administered intranasal insulin at the onset of CPR. Rodents were euthanized at 30 minutes post-return of spontaneous circulation. Regional brain homogenates of the hippocampus, cortex, and striatum were analyzed by Western blot for phosphorylated Akt. In a further study, rats were monitored for 10 days. Neurologic function score (NFS) was assessed daily and behavioral tests were conducted on days 7-10. As hypothesized, preliminary data indicated that intranasal insulin treated rats performed significantly better than control rats in all three behavioral tasks. Contrary to the hypothesis, Akt phosphorylation was not the primary mechanism of intranasal insulin-mediated neuroprotection. This study is the first to demonstrate that intranasal insulin, administered at the onset of CPR, results in significant neuroprotection. Further work is required to elucidate the mechanism of neuroprotection induced by intranasal insulin. This primary work strongly suggests that intranasal insulin could be the first highly effective neuroprotective treatment for cardiac arrest patients.
Stavnezer, Amy Jo
Chalek, Adam D., "Optimizing Intranasal Insulin Treatment During CPR Based on Delivery to the Brain, Mechanistic Target Engagement, and Neurologic Outcomes in a Rodent Model of Cardiac Arrest" (2019). Senior Independent Study Theses. Paper 8767.
Bachelor of Arts
Senior Independent Study Thesis
© Copyright 2019 Adam D. Chalek