Citation

Rodriguez UA, Zeng Y, Deyo DJ, Parsley MO, Hawkins BE, Prough DS, DeWitt D. J. Neurotrauma 2018; 35(2): 375-392.

Affiliation

U. of Texas Medical Branch, Anesthesiology , 301 University Blvd. , Suite 2A , Galveston, Texas, United States , 77555-0830 ; ddewitt@utmb.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5256

PMID

29160141

Abstract

To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry, LDF), mean arterial blood pressure (MAP) cerebral vascular resistance were measured for two hrs post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C, FJC) 24 and 48 hrs post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze, MWM) were assessed two weeks post-bTBI. Since impact TBI (i.e. non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function due, in part, to the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO‾), the effects of the administration of the ONOO‾ scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for two hrs post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and the numbers of FJC-positive cells in the brain and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend towards increased cerebral perfusion, suggesting that ONOO‾ may contribute to blast-induced cerebral vascular dysfunction.

Language: en

Keywords

LEARNING AND MEMORY; NEURONAL CELL DEATH; OXIDATIVE STRESS; TRAUMATIC BRAIN INJURY; VASCULAR REACTIVITY