Abstract 195: Sulforaphane Protects Against Subarachnoid Hemorrhage and Alters the Expression of Inflammatory and Extracellular Matrix Remodeling Genes in a Mouse Model of Intracranial Aneurysm

Abstract

Introduction: Oxidative stress has been shown to play an important role in the pathogenesis of intracranial aneurysm (IA). Sulforaphane is an isothiocyanate that exhibits antioxidant properties via the Nrf2 transcription factor. We tested whether sulforaphane would protect against IA formation and subarachnoid hemorrhage (SAH) in a mouse model. Methods: C57BL/6 mice were treated intraperitoneally with either 0.5mg/kg/day of sulforaphane (treatment group, n = 32) or a vehicle solution (control group, n = 26) prior to being subjected to a well-established IA induction protocol involving unilateral nephrectomy, mineralocorticoid administration, and intracranial injection of elastase. Sulforaphane/vehicle treatments were begun seven days prior to elastase injection, and continued daily for the duration of the experiment. Animals were followed for 14 days until sacrifice, with measurement of the number of aneurysms formed and ruptured in each animal. Intracranial vessel tissue was collected, pooled, and analyzed using real-time PCR (RT-PCR) with experiments performed in triplicate (n = 3). Results: There was a lower incidence of IA in the treatment group (1.06 +/- 0.24 per animal) than in the control group (1.54 +/- 0.33), but this trend did not reach significance. The incidence of SAH in the treatment group (0.53 +/- 0.09 per animal) was approximately 50% lower than in the control group (1.08 +/- 0.21, p = 0.012). RT-PCR showed significant (p < 0.05) differences in the expression of interferon gamma, matrix metalloproteinase 9, collagen Ia2, interleukin-6, myosin heavy chain, and SM22 between the treatment and control groups. Conclusions: Treatment with sulforaphane resulted in a significantly lower incidence of SAH in a mouse model of IA. The expression of genes involved in inflammation and extracellular matrix remodeling were altered by sulforaphane administration.