Novel Tissue Protector for Subarachnoid Hemorrhage

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DESCRIPTION (provided by applicant): There are approximately 30,000 new cases of aneurysmal subarachnoid hemorrhage (SAH) in this country, making it a significant health care problem. Despite advances in the medical and surgical care of patients with SAH, this condition still has a high morbidity and mortality, with a 30 day mortality of nearly 50%. In order to examine the pathophysiology of vasospasm following SAH and to take advantage of transgenic technology, we recently characterized a murine model of SAH. This model is an extension of the standard monofilament middle cerebral artery occlusion (MCAO) model performed in our lab and by others around the world (Parra et al. 2002). Using this model, we now demonstrate that animals expressing the epsilon 4 isoform of apolipoprotein-E (apoE4) are significantly more impaired on behavioral tests following SAH than their apoES counterparts. This situation is similar to Alzheimer's disease where patients expressing apoE4 are significantly more impaired and have an earlier age of onset than their apoES counterparts. Cognosci has developed novel mimetic peptides of apoE holo-protein which appear to retain the anti-inflammatory and neuroprotective properties of apoE holo-protein. In pilot studies, we show that 1 of these peptides, COG1410, can significantly improve survival when administered following SAH, compared to animals receiving SAH and saline vehicle as a control. Based on these pilot studies, we now wish to fully test the ability of apoE peptide mimetics to inhibit the behavioral and vasospastic deficits that follow experimental application of subarachnoid hemorrhage in a mouse model.