Mitochondrial transplantation following cardiopulmonary resuscitation improves neurological function in rats by inducing M2-type MG/MΦ polarization

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 S100[beta] in serum, and TNF-[alpha], IL-6 in the hippocampus were decreased, while the levels of TGF-[beta] 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. Keywords: Cardiac arrest, Mitochondrial transplantation, Neurological function, Microglia, Macrophages