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

Zhang,Yujing; Yu,Peiyun; Liu,Hong; Yao,Hua; Yao,Shanglong; Yuan,Shi‑Ying; Zhang,Jian‑Cheng

doi:10.3892/ijmm.2018.3971

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

Authors:
- Yujing Zhang
- Peiyun Yu
- Hong Liu
- Hua Yao
- Shanglong Yao
- Shi‑Ying Yuan
- Jian‑Cheng Zhang
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Affiliations: Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Anesthesiology, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: November 2, 2018 https://doi.org/10.3892/ijmm.2018.3971
Pages: 413-425
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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