Abstract WP106: Remote Ischemic Per-Conditioning (RIPerC) is Protective after Embolic Stroke in Ovariectomized Female Mice

Abstract

RIPerC by sub-lethal limb ischemia is protective in multiple animal models of reperfusion injury including stroke, and in certain clinical trials. We reported that RIPerC is effective with and without IV-tPA after embolic stroke (eMCAO) in young male mice ( Hoda et al; Stroke. 2012: MS ID# 660373; in press ). Our objective here was to determine if RIPerC is also effective in ovariectomized (OVX) female mice. Methods: eMCAO was induced in 68 WT C57/BL OVX females by injecting fibrin-rich clot into the right hemisphere, and occlusion was confirmed with laser Doppler instruments (LDI). Animals were randomized for the treatments after eMCAO and outcome measurements were blindly performed. RIPerC therapy or sham procedure was performed non-invasively using a rodent blood pressure cuff on the left hind limb at 2 hrs post-eMCAO (4 cycles/ each cycle 10 minutes/ 10 minutes interval). Either IV-tPA or IV-saline was infused at 4 hours post-eMCAO. Cerebral blood flow (CBF) by LDI and plasma nitric oxide (NO) was measured at 6 hours post-eMCAO. At 24 hours post-eMCAO, Bederson neurological deficit score (NDS) was assessed, and infarct size was estimated by TTC-staining. Results: RIPerC alone significantly improved the CBF, plasma NO level and NDS (P<0.05), and also reduced the infarct size (Relative reduction ~31%; P<0.01) as compared to eMCAO control group. IV-tPA alone at 4 hours post-eMCAO neither improved NDS nor reduced the infarct, although IV-tPA improved the CBF as compared to eMCAO control group due to its recanalization effects (P<0.01). In comparison to IV-tPA alone treatment, RIPerC combination with IV-tPA did not show significant improvement in CBF. But when compared to eMCAO control group, the combination therapy showed further improvements in CBF at 6 hours post-eMCAO (P<0.001). Combination therapy also significantly improved the NDS (P<0.05) and reduced the infarct size (Relative reduction ~21%; P<0.05) as compared to eMCAO control group at 24 hours post-eMCAO. Conclusion: RIPerC is an effective therapy after eMCAO in females. Further work is needed to determine the effectiveness of RIPerC in aged animals and in animals with comorbidities.