Human umbilical cord blood mononuclear cells ameliorate ischemic brain injury via promoting microglia/macrophages M2 polarization in MCAO Rats

Exp Brain Res. 2023 Jun;241(6):1585-1598. doi: 10.1007/s00221-023-06600-1. Epub 2023 May 4.

Abstract

Cerebral infarction is one of the most prevalent cerebrovascular disorders. Microglia and infiltrating macrophages play a key role in regulating the inflammatory response after ischemic stroke. Regulation of microglia/macrophages polarization contributes to the recovery of neurological function in cerebral infarction. In recent decades, human umbilical cord blood mononuclear cells (hUCBMNCs) have been considered a potential therapeutic alternative. However, the mechanism of action is yet unclear. Our study aimed to explore whether hUCBMNCs treatment for cerebral infarction is via regulation of microglia/macrophages polarization. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and were treated by intravenous routine with or without hUCBMNCs at 24 h following MCAO. We evaluated the therapeutic effects of hUCBMNCs on cerebral infarction by measuring animal behavior and infarct volume, and further explored the possible mechanisms of hUCBMNCs for cerebral infarction by measuring inflammatory factors and microglia/macrophages markers using Elisa and immunofluorescence staining, respectively. We found that administration with hUCBMNCs improved behavioral functions and reduced infarct volume. Rats treated with hUCBMNCs showed a significant reduction in the level of IL-6, and TNF-α and increased the level of IL-4 and IL-10 compared to those treated without hUCBMNCs. Furthermore, hUCBMNCs inhibited M1 polarization and promoted M2 polarization of microglia/macrophages after MCAO. We conclude that hUCBMNCs could ameliorate cerebral brain injury by promoting microglia/macrophages M2 polarization in MCAO Rats. This experiment provides evidence that hUCBMNCs represent a promising therapeutic option for ischemic stroke.

Keywords: Ischemic stroke; Microglia/macrophages; Neuroinflammation; Umbilical cord blood cells.

MeSH terms

  • Animals
  • Brain Injuries*
  • Brain Ischemia* / drug therapy
  • Fetal Blood
  • Humans
  • Infarction, Middle Cerebral Artery / drug therapy
  • Ischemic Stroke*
  • Macrophages
  • Male
  • Microglia
  • Rats
  • Rats, Sprague-Dawley
  • Stroke*