The Role of Spreading Depolarizations in Mild Traumatic Brain Injuries

Author

Natalie J. Pinkowski, University of New MexicoFollow

Publication Date

Spring 4-8-2024

Abstract

Mild traumatic brain injuries (mTBIs) often lead to acute symptoms like disorientation and discoordination, but the underlying mechanisms are unknown. Although most patients recover quickly from a single mTBI, repeated injuries can be debilitating. After an mTBI, a neurometabolic cascade produces metabolic burden and vulnerability. Spreading depolarizations (SDs) have been observed after mTBIs. Here we investigated SDs’ role in short-term motor behavioral deficits post-mTBI. We hypothesized that SDs contribute to the deficits, and exacerbated symptoms after repeated mTBIs. To test this, we used acute motor behavioral tests and long-term behavioral and cognitive tests after initiating SDs by mTBI, chemical, or optogenetic methods. We found SDs alone to sufficiently induce acute motor symptoms similar to mTBI, two mTBIs or two SDs exacerbate deficits, and four mTBIs lead to long term cognitive deficits. Identifying SDs as contributors to acute deficits post-mTBI suggests them as potential targets for promoting brain recovery.

Keywords

neuroscience, mouse model, mouse behavior, motor deficits, cerebral blood flow, neurometabolic

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

C. Fernando Valenzuela

Second Committee Member

Russell Morton

Third Committee Member

Erin Milligan

Fourth Committee Member

Jonathan Brigman

Fifth Committee Member

Jay Naik

Sixth Committee Member

Andrew Mayer

Recommended Citation

Pinkowski, Natalie J.. "The Role of Spreading Depolarizations in Mild Traumatic Brain Injuries." (2024). https://digitalrepository.unm.edu/biom_etds/254