Abstract

Background and Purpose: Social isolation (SI) has been linked epidemiologically with high rates of morbidity and mortality following stroke. Clinically, social support and coping strategies have been shown to be significant factors in caregiver’s health-related quality of life. In order to discover the biological mechanisms underlying the benefits of social interaction the development of pre-clinical animal models are needed. The goal of our study was to examine the effect of post stroke pair housing and SI in different behavioral paradigms, which can be used as a validated model to assess chronic functional recovery. Methods: C57BL/6 male mice (8-12 weeks) were paired for 14 days before 60 min of transient intraluminal middle cerebral artery occlusion (MCAO) or sham surgery (n=8-10/group) and randomly assigned to six different housing conditions: 1. Stroke isolated (STiso), 2. Stroke pair housed (PH) with sham, 3. Stroke PH with stroke and their respective sham controls (Gps 4, 5, and 6). Behavioral assessments (3 Chamber sociability task, tail suspension test and sucrose consumption test), were performed at 42 days (Cohort 1) or every 7Th day for 6 weeks (Cohort 2). Brain atrophy was calculated using cresyl violet staining and blood samples were collected for interleukin-6 (IL-6) measurements. Results: Post stroke PH mice, either with sham or stroke partner showed significantly higher (p<0.05) sociability after MCAO. In the 2nd cohort, a two-factor interaction ‘group versus days’ showed a significant difference between post stroke SI and PH groups (F 3,24 = 5.41; p< 0.01, RM ANOVA with Bonferroni correction). Post stroke SI mice showed reduced sucrose consumption (p<0.05) and increased immobility (p<0.05) indicating a depressive phenotype. Post stroke SI mice had significantly more tissue loss (40.8 ± 1.3% in SI vs. 17.5 ± 1.5% in PH; p<0.001) and showed higher levels of IL-6, a biomarker of social stress and inflammation. Conclusions: Our findings suggest that post stroke isolation reduces sociability and exacerbates depressive behavior, whereas pair housing aids early functional recovery. Moreover, the sociability (“empathy”) task can be a useful model for chronic post stroke behavioral recovery.

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