PT  - JOURNAL ARTICLE
AU  - Zhang, Xuyang
AU  - Zhang, Qingzhu
AU  - Zhang, Qian
AU  - Wang, Haomiao
AU  - Yin, Yi
AU  - Li, Huanhuan
AU  - Huang, Qianying
AU  - Guo, Chao
AU  - Zhong, Jun
AU  - Zhou, Tengyuan
AU  - Chen, Yujie
AU  - Chen, Zhi
AU  - Shan, Qiao
AU  - Hu, Rong
TI  - Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling
AID  - 10.1523/ENEURO.0021-24.2024
DP  - 2024 Jun 01
TA  - eneuro
PG  - ENEURO.0021-24.2024
VI  - 11
IP  - 6
4099  - http://www.eneuro.org/content/11/6/ENEURO.0021-24.2024.short
4100  - http://www.eneuro.org/content/11/6/ENEURO.0021-24.2024.full
SO  - eNeuro2024 Jun 01; 11
AB  - Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.