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Published on: January 18, 2016
Fecal microbiota transplantation alleviates neuronal Apoptosis, necroptosis and reactive microglia activation after
Dingzhi Chen1, Jieqiong Xie1, Xueyuan Chen1
1Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Objective:
This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.
Methods:
A total of fifty male Sprague-Dawley rats were categorized into four groups: Sham, MCAO, MCAO+vehicle and FMT. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining.Additionally, Western blot and immunofluorescence were used to detect the expression levels of Apoptotic and Necroptosis markers in neurons of ischemic brain tissue, and immunofluorescence was used to analyze the degree of activation of microglia.
Results:
FMT group exhibited a decline in neurological function score compared to the MCAO and MCAO + vehicle group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the SHAM group, the MCAO group displayed a significant increase in the expression levels of necroptosis-related proteins Phospho-RIP1, Phospho-RIP3, Phospho-MLKL, apoptotic proteins Bax and Cleaved caspase-3, and the iNOS positive microglia in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05).Conversely, compared to the MCAO + vehicle group, the FMT group showed decreased expression levels of Phospho-RIP1, Phospho-RIP3, Phospho-MLKL, Bax, Cleaved caspase-3, and iNOS-positive microglia, while the expression of Bcl-2 was increased.
Conclusion:
Fecal microbiota transplantation offers a promising approach to improving neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and the polarization of inflammatory microglial cells.
Insights
Fecal microbiota transplantation (FMT) improved neurological function in ischemic stroke rats by reducing brain infarcts. FMT inhibited neuronal apoptosis, necroptosis, and inflammatory microglial activation, offering a promising therapeutic strategy.
Area of Science:
- Neuroscience
- Gastroenterology
- Regenerative Medicine
Background:
- Ischemic stroke leads to significant neurological deficits.
- Fecal microbiota transplantation (FMT) is an emerging therapy with potential in neurological disorders.
- Understanding the mechanisms of FMT in stroke recovery is crucial.
Purpose of the Study:
- To investigate the mechanisms by which FMT improves neurological function in rats post-ischemic stroke.
- To evaluate the effects of FMT on neuronal apoptosis, necroptosis, and microglial activation.
Main Methods:
- Fifty male Sprague-Dawley rats were divided into Sham, MCAO, MCAO+vehicle, and FMT groups.
- Neurological function and infarct volume were assessed using scoring and TTC staining.
- Western blot and immunofluorescence detected apoptosis/necroptosis markers and microglial activation.
Main Results:
- FMT group showed reduced neurological deficit scores and infarct volume compared to control groups (P < 0.05).
- FMT decreased the expression of necroptosis (Phospho-RIP1/3, Phospho-MLKL) and apoptosis (Bax, Cleaved caspase-3) markers, while increasing Bcl-2.
- FMT reduced iNOS-positive microglia, indicating decreased inflammatory activation.
Conclusions:
- Fecal microbiota transplantation demonstrates therapeutic potential for ischemic stroke in rats.
- FMT ameliorates stroke-induced brain injury by inhibiting neuronal cell death pathways.
- FMT modulates microglial polarization, reducing neuroinflammation and promoting recovery.
