Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice
S G Kernie1, T M Erwin, L F Parada
1Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA. Steven.Kernie@utsouthwestern.edu
Abstract:
The persistence of neural stem cells into adulthood has been an area of intense investigation in recent years. There is limited knowledge about how an acquired brain injury might affect the ability of neural precursor cells to proliferate and repopulate injured areas. In the present study we utilize a controlled cortical impact model of traumatic brain injury in adult mice and subsequent BrdU labeling to demonstrate that there is significant proliferation of neural precursors in response to traumatic brain injury in areas both proximal and distal to the injury site. The fate of the proximal proliferation is almost exclusively astrocytic at 60-days post injury and demonstrates that newly generated cells make up much of the astrogliotic scar. Moreover, in areas more distal from the injury site, neurogenesis occurs within the granular layer of the dentate gyrus at a level more than five-fold greater than in controls. These data demonstrate that neural proliferation plays key roles in the remodeling that occurs after traumatic brain injury and suggests a mechanism as to how functional recovery after traumatic brain injuries continues to occur long after the injury itself.
Insights
Traumatic brain injury stimulates neural precursor cell proliferation. Newly formed cells contribute to scar tissue and increase neurogenesis in specific brain regions, aiding recovery.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Regenerative Medicine
Background:
- Neural stem cells persist into adulthood, but their response to acquired brain injury is poorly understood.
- Investigating how traumatic brain injury (TBI) impacts neural precursor cell proliferation and tissue repair is crucial.
Purpose of the Study:
- To examine the proliferation and fate of neural precursor cells following traumatic brain injury in adult mice.
- To determine the impact of TBI on neurogenesis in the dentate gyrus.
Main Methods:
- Utilized a controlled cortical impact model to induce TBI in adult mice.
- Employed Bromodeoxyuridine (BrdU) labeling to track cell proliferation and fate.
- Analyzed cell populations proximal and distal to the injury site at 60 days post-injury.
Main Results:
- Significant proliferation of neural precursors was observed both near and far from the TBI site.
- Cells proliferating near the injury predominantly differentiated into astrocytes, forming part of the astrogliotic scar.
- Neurogenesis in the dentate gyrus granular layer increased over five-fold compared to control levels.
Conclusions:
- Neural precursor cell proliferation is a key response to TBI, contributing to tissue remodeling.
- The generation of new neurons in the dentate gyrus may underlie long-term functional recovery after TBI.
- These findings highlight the brain's capacity for repair and suggest therapeutic targets for TBI recovery.
