Stem cell restores thalamocortical plasticity to rescue cognitive deficit in neonatal intraventricular hemorrhage

Exp Neurol. 2021 Aug;342:113736. doi: 10.1016/j.expneurol.2021.113736. Epub 2021 May 1.

Abstract

Severe neonatal intraventricular hemorrhage (IVH) patients incur long-term neurologic deficits such as cognitive disabilities. Recently, the intraventricular transplantation of allogeneic human umbilical cord blood-derived mesenchymal stem cells (MSCs) has drawn attention as a therapeutic potential to treat severe IVH. However, its pathological synaptic mechanism is still elusive. We here demonstrated that the integration of the somatosensory input was significantly distorted by suppressing feed-forward inhibition (FFI) at the thalamocortical (TC) inputs in the barrel cortices of neonatal rats with IVH by using BOLD-fMRI signal and brain slice patch-clamp technique. This is induced by the suppression of Hebbian plasticity via an increase in tumor necrosis factor-α expression during the critical period, which can be effectively reversed by the transplantation of MSCs. Furthermore, we showed that MSC transplantation successfully rescued IVH-induced learning deficits in the sensory-guided decision-making in correlation with TC FFI in the layer 4 barrel cortex.

Keywords: Barrel cortex; Functional MRI (fMRI); Intraventricular hemorrhage; Mesenchymal stem cell; Sensory-guided decision making; Thalamocortical input.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiology*
  • Cerebral Intraventricular Hemorrhage / diagnostic imaging
  • Cerebral Intraventricular Hemorrhage / physiopathology
  • Cerebral Intraventricular Hemorrhage / therapy*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / therapy*
  • Excitatory Postsynaptic Potentials / physiology
  • Humans
  • Inhibitory Postsynaptic Potentials / physiology
  • Magnetic Resonance Imaging / methods
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Thalamus / diagnostic imaging
  • Thalamus / physiology*