Abstract WP263: Early Brain Injury After Subarachnoid Hemorrhage and It’s Potential Role in Epileptogenesis

Abstract

Introduction: Subarachnoid hemorrhage (SAH) accounts for up to 5% of strokes each year and has a mortality around 40%. Early brain injury (EBI) develops within the first 72 hours of the SAH and involves neuroinflammation, activation of platelets and clotting factors, blood-brain barrier dysfunction, and neuronal loss. These changes set the stage for the development of further delayed brain injury and long-term impairments such as the development of seizures which is common after SAH. In this study we investigate the association of EBI and epileptogenesis. Methods: Using the endovascular perforation (EVP) model of SAH in rats, our lab has performed histological studies of EBI for markers including Iba-1 (inflammation), fibrinogen (microthrombosis), EBA (vascular integrity), and Flurojade B (FJB, neuronal degeneration). We coupled the EVP model with the implantation of subdural electrodes for long-term video electroencephalography (EEG) to characterize the development of interictal spikes and seizures following SAH. The EEG activity was continuously monitored for 4 months post-SAH. Results: Results of our study show a two- to three-fold increase in immunoreactivity of Iba-1, fibrinogen, EBA, and FJB following SAH compared to sham controls. EEG analysis demonstrated the presence of frequent interictal spikes during the first week post-SAH that often cluster and are periodic. By 3-4 weeks after SAH, clinical and subclinical seizures are observed that then increase in frequency and duration over time. Conclusions: This is the first study using long-term EEG monitoring to investigate the occurrence of seizures in the animal model of SAH. EBI after SAH is multifactorial and likely drives long-term deficits such as the development of a chronic epileptic condition. Neuroinflammation is a potential driver of epileptogenesis post-SAH. The use of immunomodulatory drugs in the late development of seizures in SAH may warrant further investigation.