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 study proposes 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 euvolemic hyponatremia, was investigated and showed promising results to reduce cerebral edema on post-ischemic stroke in a murine model.
Methods: Temporary intraluminal MCA occlusion model (tMCAO) was performed in two experimental groups of male C57BL/6 mice aged between 8 to 12 weeks. Single dose of intraperitoneal (IP) Conivaptan 10mg/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 5% dextrose intraperitoneally (single dose). Both treatments were administered at 30 minutes of MCA occlusion. Brain sections were stained with 1% TTC 24 hours after tMCAO to measure brain edema via calculation.
Results: Brain edema average in Conivaptan group was 0.105±0.066mm3 and in control group was 0.275±0.068mm3. Conivaptan demonstrated statistically significant potential to reduce brain edema 24 hours post tMCAO (p = 0.011).
Conclusions: Conivaptan significantly reduced cerebral edema in the murine MCA occlusion model. These encouraging results support the effectiveness of Conivaptan in brain edema and neuro-protection in the setting of MMS.
Patient Care: By proofing the efficacy of Conivaptan in preventing and/or treating brain edema in ischemic stroke murine model, this drug can potentially help treating patients undergoing devastating outcomes regarding malignant MCA stroke.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Know about the early measures facing malignant MCA stroke, 2) The role of vasopressin receptor antagonists, specifically Conivaptan, in prevention and treatment of brain edema in ischemic stroke.