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Updated: Oct 12, 2025
A Model for Encephalomyosynangiosis Treatment after Middle Cerebral Artery Occlusion-Induced Stroke in Mice
Published on: June 22, 2022
OM-MSCs Alleviate the Golgi Apparatus Stress Response following Cerebral Ischemia/Reperfusion Injury via the
Jialin He1, Jianyang Liu1, Yan Huang2
1Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China.
Abstract:
The mechanism of Golgi apparatus (GA) stress responses mediated by GOLPH3 has been widely studied in ischemic stroke, and the neuroprotection effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) against cerebral ischemia/reperfusion injury (IRI) has been preliminarily presented. However, the exact role of OM-MSCs in the GA stress response following cerebral IRI remains to be elucidated. In the present study, we used an oxygen-glucose deprivation/reoxygenation (OGD/R) model and reversible middle cerebral artery occlusion (MCAO) model to simulate cerebral IRI in vitro and in vivo. Our results showed that the level of GOLPH3 protein, reactive oxygen species (ROS), and Ca2+ was upregulated, SPCA1 level was downregulated, and GA fragmentation was increased in ischemic stroke models, and OM-MSC treatment clearly ameliorated these GA stress responses in vitro and in vivo. Subsequently, the knockdown of PEDF in OM-MSCs using PEDF-specific siRNA further demonstrated that secretion of PEDF in OM-MSCs protected OGD/R-treated N2a cells and MCAO rats from GA stress response. Additionally, rescue experiment using specific pathway inhibitors suggested that OM-MSCs could promote the phosphorylation of the PI3K/Akt/mTOR pathway, thereby mitigating OGD/R-induced GA stress response and excessive autophagy. In conclusion, OM-MSCs minimized the GA stress response following cerebral IRI, at least partially, through the PEDF-PI3K/Akt/mTOR pathway.
Insights
Olfactory mucosa mesenchymal stem cells (OM-MSCs) protect against brain injury by reducing Golgi apparatus stress. OM-MSCs achieve this neuroprotection via PEDF secretion and activating the PI3K/Akt/mTOR pathway.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Golgi apparatus (GA) stress, mediated by GOLPH3, is implicated in ischemic stroke.
- Olfactory mucosa mesenchymal stem cells (OM-MSCs) show preliminary neuroprotective effects against cerebral ischemia/reperfusion injury (IRI).
- The precise role of OM-MSCs in GA stress following cerebral IRI requires further investigation.
Purpose of the Study:
- To elucidate the role of OM-MSCs in mitigating Golgi apparatus stress responses after cerebral IRI.
- To investigate the underlying mechanisms, including the involvement of PEDF and the PI3K/Akt/mTOR pathway.
Main Methods:
- Utilized in vitro (oxygen-glucose deprivation/reoxygenation - OGD/R) and in vivo (reversible middle cerebral artery occlusion - MCAO) models to simulate cerebral IRI.
- Assessed GA stress markers (GOLPH3, ROS, Ca2+, SPCA1, GA fragmentation).
- Investigated the effect of OM-MSC treatment, PEDF knockdown in OM-MSCs, and pathway inhibitors (PI3K/Akt/mTOR).
Main Results:
- Cerebral IRI models exhibited increased GOLPH3, ROS, Ca2+, GA fragmentation, and decreased SPCA1.
- OM-MSC treatment ameliorated these GA stress responses both in vitro and in vivo.
- OM-MSCs protected cells and rats from GA stress, mediated by PEDF secretion.
- OM-MSCs promoted PI3K/Akt/mTOR pathway phosphorylation, reducing OGD/R-induced GA stress and excessive autophagy.
Conclusions:
- OM-MSCs effectively minimize Golgi apparatus stress following cerebral IRI.
- This neuroprotection is, at least partially, achieved through the PEDF-PI3K/Akt/mTOR signaling pathway.
- OM-MSCs represent a potential therapeutic strategy for cerebral IRI by modulating GA stress responses.
