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

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:

• Traumatic brain injury
• neurogenic niche
• Thrombospondin 4 (Thbs4)
• SDF-1
• neuronal regeneration

Acknowledgments

This work was supported by grants (2018YFA0107900, 31771491, 81471242, 81601069) from the National Nature Science Foundation and Ministry of Science and Technology of China.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by the National Nature Science Foundation [81601069,31771491]; Ministry of Science [2018YFA0107900]; and Technology of China [81471242].