Intracardiac Injection of Dental Pulp Stem Cells After Neonatal Hypoxia-Ischemia Prevents Cognitive Deficits in Rats

Neurochem Res. 2018 Dec;43(12):2268-2276. doi: 10.1007/s11064-018-2647-z. Epub 2018 Sep 25.

Abstract

Neonatal hypoxia-ischemia (HI) is associated to cognitive and motor impairments and until the moment there is no proven treatment. The underlying neuroprotective mechanisms of stem cells are partially understood and include decrease in excitotoxicity, apoptosis and inflammation suppression. This study was conducted in order to test the effects of intracardiac transplantation of human dental pulp stem cells (hDPSCs) for treating HI damage. Seven-day-old Wistar rats were divided into four groups: sham-saline, sham-hDPSCs, HI-saline, and HI-hDPSCs. Motor and cognitive tasks were performed from postnatal day 30. HI-induced cognitive deficits in the novel-object recognition test and in spatial reference memory impairment which were prevented by hDPSCs. No motor impairments were observed in HI animals. Immunofluorescence analysis showed human-positive nuclei in hDPSC-treated animals closely associated with anti-GFAP staining in the lesion scar tissue, suggesting that these cells were able to migrate to the injury site and could be providing support to CNS cells. Our study evidence novel evidence that hDPSC can contribute to the recovery following hypoxia-ischemia and highlight the need of further investigation in order to better understand the exact mechanisms underlying its neuroprotective effects.

Keywords: Cellular therapy; Dental pulp stem cells; Memory; Neonatal hypoxia-ischemia; hDPSCs.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / prevention & control*
  • Dental Pulp / cytology
  • Dental Pulp / physiology
  • Dental Pulp / transplantation*
  • Female
  • Heart Ventricles
  • Humans
  • Hypoxia-Ischemia, Brain / complications
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / therapy*
  • Injections
  • Male
  • Maze Learning / physiology
  • Pregnancy
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Stem Cell Transplantation / methods*
  • Stem Cells / physiology