Abstract TP169: Cannabidiol as a Therapy for Experimental Subarachnoid Hemorrhage

Abstract

Subarachnoid hemorrhage (SAH), commonly caused by a ruptured aneurysm, carries a high rate of disability and death. Patients who survive the initial bleed continue to be at risk of secondary insults. Preclinical studies demonstrate SAH induces dysregulation of the cerebrovasculature and increases neuroinflammation, which contributes to early brain injury and delayed cerebral ischemia. Few treatment options currently exist for SAH patients, making it imperative to identify novel therapies to improve outcomes following SAH. Cannabidiol (CBD) has gained attention for its potential therapeutic properties and widespread mechanistic actions. First utilized for the treatment of pain, preclinical studies demonstrate CBD has anti-inflammatory, neuroprotective, and vascular stabilization properties in experimental models of injury. Our objective was to determine the novel therapeutic potential of CBD for SAH injury. Male and female C57Bl/6J mice were subjected to the endovascular perforation model of SAH and treated daily with CBD (10 mg/kg; intraperitoneal (i.p.)) or vehicle control. We demonstrate that fewer mice developed ischemic cortical infarcts following CBD treatment compared to controls, indicating CBD reduces the potential development of delayed cerebral ischemia following SAH. Consistently, we demonstrate a significantly lower mortality rate in animals treated with CBD following SAH. We also detected a CBD-mediated decrease in astrocyte and microglia activation 1-7 days post-injury, as well as reduced levels of iron (Prussian blue), which contributes to apoptosis and cognitive dysfunction. Overall, treatment with CBD following experimental SAH may act to normalize vascular and inflammatory responses to decrease mortality, risk of delayed infarcts, and neurodegeneration, though further investigation is required.