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Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
Mitochondrial transplantation following cardiopulmonary resuscitation improves neurological function in rats by
Jie Zhu1, Zhen Wang1, Mengda Xu2
1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
Aim:
Explore the effects of mitochondrial transplantation (MT) after cardiopulmonary resuscitation (CPR) on the polarization of microglia/macrophages (MG/MΦ) and neurological function.
Methods:
Seventy-five Sprague-Dawley rats were randomly divided into five groups: sham, normal saline (NS), vehicle, mitochondria (Mito), and non-functional mitochondria (N-Mito) group. Rats in sham group underwent surgical procedures without cardiac arrest, while the other four groups underwent cardiac arrest and CPR, and then received NS, respiration buffer, mitochondrial suspension or non-functional mitochondria, immediately after the restoration of spontaneous circulation (ROSC). The number of mitochondria in the hippocampus, the morphology and structure of mitochondria in MG/MΦ, the phenotype of MG/MΦ, and hippocampal tissue injury, neuroinflammation, and neuronal apoptosis were detected on days 1 and 3 after ROSC. Neurodeficit score (NDS) was performed on days 1, 3, 7, 15 and 30 after ROSC.
Results:
Compared with other groups, the number of mitochondria in the hippocampus was increased, and the morphology and structure of mitochondria in MG/MΦ were significantly improved in the Mito group. Our results show higher expression of M2-type markers in MG/MΦ and decreased hippocampal tissue damage in the Mito group. Levels of NSE and S100β in serum, and TNF-α, IL-6 in the hippocampus were decreased, while the levels of TGF-β and IL-10 were increased in the Mito group. Apoptosis rate of neurons in the Mito group was decreased and the NDS of the Mito group was higher than the other groups.
Conclusions:
Exogenous MT can improve neurological function after CPR by promoting the polarization of MG/MΦ to M2-type cells, and this could be a potential method for brain protection after CPR.
Insights
Mitochondrial transplantation (MT) improved neurological function after cardiopulmonary resuscitation (CPR). MT promoted microglia/macrophages (MG/MΦ) to M2-type cells, offering potential brain protection post-CPR.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Cardiopulmonary resuscitation (CPR) can lead to neurological damage.
- Microglia/macrophages (MG/MΦ) play a crucial role in neuroinflammation and brain injury post-CPR.
- Modulating MG/MΦ polarization is a potential therapeutic strategy for brain protection.
Purpose of the Study:
- To investigate the effects of mitochondrial transplantation (MT) on microglia/macrophages (MG/MΦ) polarization after CPR.
- To evaluate the impact of MT on neurological function and brain injury following CPR.
- To explore MT as a potential neuroprotective therapy after CPR.
Main Methods:
- Seventy-five rats underwent cardiac arrest and CPR, followed by treatment with saline, vehicle, functional mitochondria (Mito), or non-functional mitochondria (N-Mito).
- Mitochondrial quantity and morphology in the hippocampus, MG/MΦ phenotype, hippocampal tissue injury, neuroinflammation, and neuronal apoptosis were assessed.
- Neurological deficit score (NDS) was measured at multiple time points post-CPR.
Main Results:
- Mitochondrial transplantation (Mito group) increased mitochondrial numbers and improved mitochondrial morphology in hippocampal MG/MΦ.
- MT promoted MG/MΦ polarization towards an M2-type phenotype, reducing hippocampal tissue damage and neuroinflammation.
- The Mito group exhibited decreased neuronal apoptosis, reduced levels of inflammatory markers (TNF-α, IL-6), and improved neurological deficit scores.
Conclusions:
- Exogenous mitochondrial transplantation (MT) enhances neurological function after CPR.
- MT promotes MG/MΦ polarization to M2-type cells, contributing to neuroprotection.
- Mitochondrial transplantation represents a promising therapeutic approach for brain protection following CPR.
