Enriched Housing Rehabilitation for Stroke Recovery in Spontaneously Hypertensive Rats
Authors: Wolf Victoria L. , Abdul Yasir , Li Weiguo , Ergul Adviye 
Published: May 2022

Long‐term disability due to stroke is a major global health burden, and there is an urgent need for interventions targeting the post‐acute phase of stroke to improve motor and cognitive deficits. Hypertension is a major contributor to overall risk for stroke and is associated with worse functional outcomes and mortality. Previous studies from our laboratory suggest that the spontaneously hypertensive rat (SHR) model of experimental hypertension develops profound, progressive post‐stroke cognitive impairment. Enriched housing (EH) conditions have shown promise as a rehabilitation strategy to enhance brain plasticity and improve behavior in preclinical studies using relatively young, healthy, adult male animals. However, the impact of hypertension on stroke recovery outcomes in response to EH remains unknown. The goal of this study was to test EH conditions for stroke rehabilitation in an established preclinical model of hypertension. We hypothesized that EH would improve the sensorimotor and cognitive recovery response to stroke in male SHRs compared to standard housing (SH) conditions. SHRs (aged 17w) were subjected to either sham or 60‐min. middle cerebral artery occlusion (MCAO) surgery to induce stroke. Stroke severity was controlled for using the following inclusion criteria: adhesive removal time (ART) > 35 sec. and either a modified Bederson score <= 6 or weight loss > 10%). Animals were then randomized to EH or SH conditions. EH conditions consisted of a novel environment to promote exercise and social interaction and was implemented for 2 hrs/day, 5 days/week for 4w starting 1w after surgery. Blood pressure was monitored by tail‐cuff plethysmography at baseline, 1, 3, and 7w post‐surgery. Animals were followed for an additional 4w after rehabilitation intervention for behavioral outcome measures. Motor recovery was assessed using ART (Figure 1), and novel object recognition (NOR, Figure 2) and 2‐trial Y‐maze were used to determine cognitive recovery. Stroked animals had significantly increased adhesive removal times at 3d and 6w post‐MCAO compared to sham animals, but EH conditions did not significantly impact this sensorimotor deficit. Stroke+EH animals had a significant decrease from their pre‐stroke recognition indices 1w post‐stroke compared to Sham+EH animals, suggesting there may have been some acute deficits in non‐spatial working memory. There were no significant differences among groups in time spent in the novel arm of the 2‐trial y‐maze, suggesting that stroke did not alter spatial working memory. Overall, these findings suggest that there are significant sensorimotor deficits post‐stroke, and the mild improvement in ART over time in stroked hypertensive animals occurs independently of EH. Cognitive deficits were similar in stroke and sham animals, regardless of rehabilitation, except for 1w post‐stroke, which is likely before EH would have had a significant impact on non‐spatial working memory. However, this effect might be skewed by a significant increase in NOR exploration time in Sham+EH animals. Unlike in previous studies in our laboratory, 60‐min. MCAO did not appear to induce significant post‐stroke cognitive impairment in these hypertensive animals compared to sham procedure.