Display options
Cite
George KK, Heithoff BP, Shandra O, et al. Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction. J Neurotrauma. 2021;doi: 10.1089/neu.2021.0204.
George, K. K., Heithoff, B. P., Shandra, O., & Robel, S. (2021). Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction. Journal of neurotrauma, . https://doi.org/10.1089/neu.2021.0204
George, Kijana Kaaria, et al. "Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction." Journal of neurotrauma vol. (2021). doi: https://doi.org/10.1089/neu.2021.0204
George KK, Heithoff BP, Shandra O, Robel S. Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction. J Neurotrauma. 2021 Nov 22; doi: 10.1089/neu.2021.0204. Epub 2021 Nov 22. PMID: 34806422.
Copy Download .nbib Format: NLM
Share it on

J Neurotrauma. 2021 Nov 22; doi: 10.1089/neu.2021.0204. Epub 2021 Nov 22.

Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction.

Journal of neurotrauma

Kijana Kaaria George, Benjamin Patrick Heithoff, Oleksii Shandra, Stefanie Robel

Affiliations

  1. Virginia Tech Carilion Research Institute, 145763, Roanoke, Virginia, United States.
  2. Virginia Tech, 1757, Graduate Program in Translational Biology, Medicine, and Health, Blacksburg, Virginia, United States; [email protected].
  3. Virginia Tech, 1757, Department of Biological Sciences, Blacksburg, Virginia, United States; [email protected].
  4. Virginia Tech Carilion Research Institute, 145763, Roanoke, Virginia, United States; [email protected].
  5. University of Alabama at Birmingham Department of Cell Biology, 189176, Department of Cell, Developmental and Integrative Biology, Birmingham, Alabama, United States; [email protected].

PMID: 34806422 DOI: 10.1089/neu.2021.0204

Abstract

Mild traumatic brain injury/ concussion (mTBI) accounts for 70-90% of all reported TBI cases and causes long-lasting neurological consequences in 10 to 40% of patients. Recent clinical studies revealed increased blood-brain barrier (BBB) permeability in mTBI patients, which correlated with secondary damage after mTBI. However, the cascade of cellular events initiated by exposure to blood-borne factors resulting in sustained damage are not fully resolved. We previously reported that astrocytes respond atypically to mTBI rapidly losing many proteins essential to their homeostatic function while classic scar formation does not occur. Here, we tested the hypothesis that mTBI-induced BBB damage causes atypical astrocytes through exposure to blood-borne factors. Using a mTBI mouse model, 2-photon imaging, an endothelial cell-specific genetic ablation approach, and serum-free primary astrocyte cultures, we demonstrated that areas with atypical astrocytes coincide with BBB damage and that exposure of astrocytes to plasma proteins is sufficient to initiate loss of astrocyte homeostatic proteins. While mTBI resulted in frequent impairment of both physical and metabolic BBB properties and leakage of small-sized blood-borne factors, deposition of the coagulation factor fibrinogen or vessel rupture were rare. Surprisingly, even months after mTBI BBB repair did not occur in areas with atypical astrocytes. Together, these findings implicate that even relatively small BBB disturbances are sustained long-term and render nearby astrocytes dysfunctional, likely at the cost of neuronal health and function.

Keywords: BLOOD-BRAIN BARRIER DYSFUNCTION; GLIA CELL RESPONSE TO INJURY; IMMUNOHISTOCHEMISTRY; TRAUMATIC BRAIN INJURY; blood brain barrier

Publication Types