Downregulation of Thbs4 caused by neurogenic niche changes promotes neuronal regeneration after traumatic brain injury

Neurol Res. 2020 Aug;42(8):703-711. doi: 10.1080/01616412.2020.1795590. Epub 2020 Jul 20.

Abstract

Objective: Following brain injury, the neurogenic niche provides a permissive cue for iatrogenesis rather than neurogenesis; reactive astrocytes play essential roles in orchestrating this process, markedly forming a glial scar around the area of damaged brain tissue. The objective of this study was to alter the neurogenic niche at the injured cortex and study its impact on neurogenesis.

Methods: We constructed a stromal cell-derived factor 1 (SDF-1) gradient matrix to attract reactive astrocytes to the glial scar core.

Results: SDF-1 reacted with the astrocytes in the injured site. By changing the neurogenic niche of the injured part of the brain after traumatic brain injury (TBI), SDF-1 downregulated thrombospondin 4 (Thbs4) promoting neuronal cell regeneration and playing a beneficial role in nerve function recovery after brain injury.

Discussion: The matrix we created in this study could attract and interact with reactive glial cells and, thus, we called it a glial pump. Using the glial pump, we identified a new mechanism of brain injury repair and neuronal regeneration after TBI, which relied on Thbs4 downregulation after the altered neurogenic niche promoted neuronal regeneration and functional recovery.

Keywords: SDF-1; Thrombospondin 4 (Thbs4); Traumatic brain injury; neurogenic niche; neuronal regeneration.

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / physiology*
  • Brain Injuries, Traumatic / physiopathology*
  • Brain Regeneration*
  • Chemokine CXCL12 / metabolism
  • Down-Regulation
  • Mice, Inbred C57BL
  • Neurogenesis*
  • Thrombospondins / metabolism*

Substances

  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Thrombospondins
  • thrombospondin 4