Hyperforin improves post-stroke social isolation-induced exaggeration of PSD and PSA via TGF-β

Abstract

Stroke survivors often experience social isolation, which can lead to post-stroke depression (PSD) and post-stroke anxiety (PSA) that can compromise neurogenesis and impede functional recovery following the stroke. The present study aimed to investigate the effects and mechanisms of post-stroke social isolation-mediated PSD and PSA on hippocampal neurogenesis and cognitive function. The effects of the natural antidepressant hyperforin on post-stroke social isolation-mediated PSD and PSA were also investigated. In the present study, a model of PSD and PSA using C57BL/6J male mice was successfully established using middle cerebral artery occlusion combined with post-stroke isolated housing conditions. It was observed that PSD and PSA were more prominent in the isolated mice compared with the pair-housed mice at 14 days post-ischemia (dpi). Mice isolated 3 dpi exhibited decreased transforming growth factor-β (TGF-β) levels and impairment of hippocampal neurogenesis and memory function at 14 dpi. Intracerebroventricular administration of recombinant TGF-β for 7 consecutive days, starting at 7 dpi, restored the reduced hippocampal neurogenesis and memory function induced by social isolation. Furthermore, intranasal administration of hyperforin for 7 consecutive days starting at 7 dpi improved PSD and PSA and promoted hippocampal neurogenesis and memory function in the isolated mice at 14 dpi. The inhibition of TGF-β with a neutralizing antibody prevented the effects of hyperforin. In conclusion, the results revealed a previously uncharacterized role of hyperforin in improving post-stroke social isolation-induced exaggeration of PSD and PSA and, in turn, promoting hippocampal neurogenesis and cognitive function via TGF-β.