Current Status and Progress in Stem Cell Therapy for Intracerebral Hemorrhage

Ding, Ning; Luo, Ran; Zhang, Qian; Li, Huanhuan; Zhang, Shuixian; Chen, Huanran; Hu, Rong

doi:10.1007/s12975-023-01216-7

Cited by 3 publications

(1 citation statement)

References 164 publications

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“…NSC therapy has shown promise in treating various neurological diseases, including neurovegetative diseases ( Boese et al, 2020 ), traumatic brain injury ( Fang et al, 2022 ), and stroke ( Ding et al, 2023 ). However, the microenvironmental changes that occur after pathological damage typically impede neurogenesis and tissue repair ( Ge et al, 2023 ), resulting in neurological deficits.…”

Section: Discussionmentioning

confidence: 99%

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling

Zhang,

Zhang

et al. 2024

eNeuro

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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 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.Significance StatementIntracerebral hemorrhage (ICH) has been associated with cognitive dysfunction, yet its underlying mechanism remains elusive. Tetrahydrofolate (THF) has shown potential in promoting the proliferation of neural stem cells (NSCs), but its specific impact on cognitive recovery following ICH is still to be confirmed. Through the utilization of the Nestin-GFP genetic marker to track endogenous NSCs in mice, our study revealed that THF could regulate PTEN pathway to ameliorate cognitive impairment post-ICH by enhancing the proliferation of NSCs and sustaining neurogenesis. These findings contribute to valuable insights into the molecular mechanisms involved and suggest potential clinical applications for enhancing cognitive function recovery after ICH.

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Section: Discussionmentioning

confidence: 99%

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling

Zhang,

Zhang

et al. 2024

eNeuro

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Human-mouse chimeric brain models constructed from iPSC-derived brain cells: Applications and challenges

Zhao,

Liu,

Wang

et al. 2024

Experimental Neurology

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Evaluation on the efficacy of neural stem cells supernatant combined with AKT inhibitor in intracerebral hemorrhage model in vitro

Luo

2024

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Objective: Intracerebral hemorrhage (ICH), charactered by bleeding and subsequent cortical neuronal injury, is a kind of cerebrovascular disease with high disability and mortality. Although neural stem cells (NSC) transplantation emerges as a potential therapy for ICH by protecting injured cortical neurons, its efficacy remains limited. It is acknowledged that AKT (Protein Kinase B, PKB) inhibitors, as classical cytostatic agents, play a role in a variety of biological processes, including cell growth, proliferation, differentiation, and apoptosis. Therefore, this study aims to evaluate the combined effects of NSC supernatant and AKT inhibitors on cortical neurons in ICH. Methods: Primary cortical neurons were cultured and treated with hemin chloride (hemin) to induce ICH in vitro model. The combined strategy of both NSC supernatant and AKT inhibitor was applied. Cell viability was assessed using CCK-8 assays, and apoptosis was evaluated through Hoechst 33342/PI co-staining. Statistical analysis was conducted using SPSS 17.0 software. Results: The combination of NSC supernatant and AKT inhibitors significantly enhanced cell viability and reduced apoptosis in hemin-induced cortical neuronal injury compared to individual treatments. The synergistic effect was demonstrated by increased cell counts and viability in the NSC supernatant + AKT inhibitor group. Conclusion: NSC supernatant combined with AKT inhibitors synergistically enhances therapeutic and anti-apoptotic effects in cortical neuronal injury induced by hemin, showing a potential as a novel therapeutic strategy for neuronal injury in ICH models.

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Current Status and Progress in Stem Cell Therapy for Intracerebral Hemorrhage

Cited by 3 publications

References 164 publications

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling

Human-mouse chimeric brain models constructed from iPSC-derived brain cells: Applications and challenges

Evaluation on the efficacy of neural stem cells supernatant combined with AKT inhibitor in intracerebral hemorrhage model in vitro

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