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

J Transl Med. 2024 Nov 11;22(1):1014. doi: 10.1186/s12967-024-05815-2.

Abstract

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.

Keywords: Cardiac arrest; Macrophages; Microglia; Mitochondrial transplantation; Neurological function.

MeSH terms

  • Animals
  • Apoptosis
  • Cardiopulmonary Resuscitation*
  • Cell Polarity
  • Cytokines / metabolism
  • Heart Arrest / pathology
  • Heart Arrest / therapy
  • Hippocampus* / pathology
  • Macrophages*
  • Male
  • Microglia* / metabolism
  • Microglia* / pathology
  • Mitochondria* / metabolism
  • Nervous System / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley*

Substances

  • Cytokines