Document Type

Thesis

Date of Degree

Spring 2013

Degree Name

MS (Master of Science)

Degree In

Interdisciplinary Studies

First Advisor

Michael J. Welsh

Abstract

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3- after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a-/- mice and found reduced neurodegeneration after FPI. Both HCO3- administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

Keywords

acid, ASIC, brain injury

Pages

iv, 23 pages

Bibliography

Includes bibliographical references (pages 19-23).

Copyright

Copyright 2013 Terry Yin

Included in

Cell Biology Commons

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