Abstract W MP50: Pair Housing Reverses the Detrimental Effect of Social Isolation and Restores BDNF and MBP in Aged Mice after Stroke

Abstract

Background: Age is an important non-modifiable risk factor for stroke. Stroke rates double every decade after age 55. Social isolation (SI) exacerbates behavioural deficits, slows functional recovery and worsens histological injury after stroke in young animals, primarily by increasing the inflammatory response. However, the inflammatory response differs in aging, and whether the detrimental effects of SI are seen in aged animals is unknown. We hypothesize that acute and chronic post stroke SI will worsen stroke pathology and recovery in aged mice and pair housing (PH) will reverse these effects. Methods: Eighteen-month-old male C57BL/6 mice were pair housed (PH) for two weeks prior to stroke and randomly assigned to various housing conditions immediately after stroke. Behavioral analysis was done weekly starting at day 7. Mice were sacrificed either at 72 hours or 4 weeks after 60-minute right MCAO or sham surgery (n=9-10/group). Results: Mice isolated after stroke (ST-ISO) mice had significantly greater hemispheric infarct volume and neurological deficit scores (p<.05. n=13/group) than pair-housed (PH) stroke mice at 72 hours. SI mice that were isolated immediately after stroke showed significantly higher plasma IL-6 levels compared to PH sham (P<.001, n=13/group ) or PH stroke mice (P<.05) after 72 hour, but levels were similar by 4 weeks post-stroke (n=9-14/group). No change in tissue atrophy was seen after 4 weeks, however a significant interaction [F (1, 28) = 259.6, P<0.001] between housing and stroke was found in the Novel Object Recognition Task (NORT) at day 14. PH led to increased expression of Brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP) by IHC and western blot (n=5/group for IHC and n= 4/ western blot). Conclusions: Social isolation immediately after stroke led to enhanced injury acutely. Despite similar infarcts at 4 weeks, SI mice had delayed behavioral recovery. Pair housing led to increased expression of BDNF and myelin protein expression. Therefore, the beneficial effects of pair housing may be related to BDNF and MBP expression and enhanced recovery after injury in aged animals.