F Abukhali, V. S. Hedna, S Ansari, P Saravanapavan, S Ganji1, Peter Y. Cai, Michael F. Waters and Sylvain Dor
Scientific Tracks Abstracts: J Neurol Neurophysiol
Introduction:Middle cerebral artery (MCA) occlusion is the leading cause of ischemic stroke worldwide. ?Malignant MCA stroke? (MMS), which denotes a large infarction of the MCA territory with associated cytotoxic edema, has a mortality nearing 80%. Current treatments such as osmo-therapy and hemicraniectomy are designed to reduce post-stroke cytotoxic edema, but have substantial limitations and fail to significantly decrease morbidity and/or mortality. The current studyproposes a non- surgical alternative by using a mixed arginine vasopressin receptor antagonist as an efficient modality to prevent and treat MMS by influencing cerebral water homeostasis through modulating BBB permeability. Conivaptan (mixed V1a/V2 vasopressin receptor antagonist), which is currently FDA approved to treat euvolemichyponatremia, was investigated and showed promising results to reduce cerebral edema on post-ischemic stroke in a murine model. Methods: Temporary intraluminal MCA occlusion model (t-MCAO) was performed in two experimental groups of male C57BL/6 mice aged between 8 to 12 weeks. Single dose of intraperitoneal (IP) Conivaptan 10 mg/kg (1.2ml) premixed with 5% dextrose (5D) was administered in the treatment group (n=6). The control group (n=6) received 1.2ml of intraperitoneal 5% dextrose (single dose). Both treatments were administered at 30 minutes of MCA occlusion. Brain sections were stained with 1% TTC 24 hours after t-MCAO to measure brain edema via calculation. Results: Brain edema average in Conivaptan group was 0.1050.066 mm 3 and in control group was 0.2750.068 mm 3 . Conivaptan demonstrated statistically significant potential to reduce brain edema 24 hours post t-MCAO (p = 0.011).
