Wednesday, April 2, 2025
4/2/2025
Cannabidiol (CBD) as a Potential Therapeutic for Experimental Subarachnoid Hemorrhage - ABSTRACT Subarachnoid hemorrhage (SAH), commonly caused by a ruptured aneurysm, carries a high rate of disability and death. Preclinical studies demonstrate SAH induces dysregulation of the cerebrovasculature, which con- tributes 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. However, understanding of the effects of CBD on blood vessels in the brain is limited, and no studies have directly investigated CBD as a treatment for SAH, representing critical gaps in knowledge. The overall objectives of this application are to determine the therapeutic potential of CBD for SAH injury and identify processes by which CBD improves vascular health. The central hypothesis is that daily CBD treatment improves vascular integrity to increase cerebral blood flow (CBF) and prevent DCI, thereby improving functional outcomes and mortality following SAH. The rationale for this project is that determination of CBD’s therapeutic efficacy in SAH will generate a strong scientific framework from which new strategies for SAH therapy can be developed. The central hypothesis will be tested by pursuing two specific aims: 1) Determine CBD’s efficacy to improve functional outcomes and mortality following SAH, and 2) Identify the impact of CBD therapy on cerebral microvessel pathology follow- ing SAH. Under the first aim, multiple doses of CBD will be tested in mice following SAH injury (endovascular perforation) to determine the most effective dose that improves sensory/motor function and cognitive out- comes, and reduces mortality. For the second aim, the efficacy of CBD to reduce the development of vaso- spasm and blood-brain barrier leakage will be investigated utilizing intravital microscopy and ex vivo micro- Computed Tomography imaging. The research proposed in this application is innovative because it proposes the use of a compound with a wide variety of molecular targets capable of ameliorating multiple aspects of SAH pathology. The proposed research is significant because it is expected to provide scientific justification for the continued mechanistic investigation of CBD as a much-needed novel therapeutic for SAH patients, advancing the field of stroke research.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).