Abstract WP134: Calcium Release-activated Calcium Channel Inhibition Improves Neurological Outcome and Suppresses Inflammation in Female Mice Following Cerebral Ischemic Injury

• Published in: Stroke (1970) 2019-02, Vol.50 (Suppl_1)
• Main Authors: Mizuma, Atsushi, Kacimi, Rachid, Stauderman, Ken, Dunn, Michael J, Hebbar, Sudarshan, Yenari, Midori A
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.50.suppl_1.WP134

Abstract only Purpose: Calcium release-activated calcium (CRAC) channels activate microglia via store-operated Ca 2+ entry. We previously reported that the specific CRAC channel inhibitor (CM-EX-137) had neuroprotective effects in a model of experimental stroke due to suppression of microglial activation in male mice. However, it is well known that sex differences can influence stroke outcome as well as immune responses. Whether CRAC channel inhibition in female mice is similarly neuroprotective is unknown. The purpose of this study is to determine whether female mice respond similarly CRAC channel inhibition in a stroke model Subjects and Methods: C57/BL6 female mice, aged 2 months were subjected to distal middle cerebral artery occlusion (dMCAO) were treated with CM-EX-137 (5mg/kg IP; dMCAO-CM) or vehicle control (dMCAO-vehicle) daily for 3d. Stroke surgeries were carried out during the same phase of the estrus cycle (diestrus) to avoid potential confounds due to varying estrogen levels. These groups were also compared to sham groups. CM-EX-137 was injected immediately after occlusion and at 24 & 48h. Brains were extracted 3d post dMCAO. Neurological functions were evaluated before surgery, and 1 & 3d later. Lesion size was estimated from cresyl violet stains. Microglia and astrocyte activation were assessed using immunohistochemistry. Results: Neurological function at both 24 and 72 h post ischemia were significantly improved in dMCAO-CM group, compared with dMCAO-vehicle group (n=7/group; p