Abstract 013: Hippocampal Neuroinflammation Occurs After Focal Cerebral Ischemic Stroke That May Contribute To Post-Stroke Memory Loss

Abstract

Chronic hypertension is a leading risk factor for ischemic stroke. Post-stroke dementia occurs in up to 80% of stroke survivors, and its prevalence is increasing due to an aging population. Memory is impaired in rodent models of transient middle cerebral artery occlusion (tMCAO). However, the impact of cerebral ischemia on brain regions involved in memory that are distant from the ischemic site, such as the hippocampus, remains unclear, but may involve neuroinflammation that is known to disrupt memory. We tested the hypothesis that neuroinflammation occurs in the hippocampus after tMCAO, contributing to memory dysfunction, and is more severe during chronic hypertension. Adult normotensive male Wistar rats and spontaneously hypertensive rats (SHR) underwent 45 minutes of ischemia induced using the intravascular filament method of tMCAO and seven days of reperfusion (or sham; n=6-8/group). A novel object recognition task was used days 5-7 post-tMCAO, and recognition index calculated to assess long-term memory function. Neuroinflammation in the hippocampal CA1 region of ipsi- and contralesional hemispheres was assessed immunohistochemically: microglial activation using Iba1 staining and neuronal expression of tumor necrosis factor alpha (TNFα). Data are mean ± SEM and comparisons made via a two-way ANOVA to determine the interaction between hypertension and stroke with a post-hoc Tukey test. Sham operated SHR and Wistar rats performed similarly well in the memory task and had recognition indices 0.65-0.70. However, memory was impaired in rats that had tMCAO, with recognition indices decreasing to 0.52±0.02 in Wistar rats and 0.52±0.03 in SHR (F 1,24 =21.60; p<0.01). Ischemia increased the number of TNFα expressing neurons regardless of hypertensive status in hippocampus of ipsi- (F 1,25 =7.87; p<0.01) and contra-lesional hemispheres (F 1,25 =4.22; p<0.05). There was a significant effect of ischemia on microglial activation in the hippocampus of both SHR and Wistar rats that only occurred ipsi-lesionally (F 1,24 =5.48; p<0.05). These findings demonstrate that hippocampal neuroinflammation is present seven days after transient focal cerebral ischemia that may contribute to post-stroke memory impairment.