Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats

Mol Cell Neurosci. 2014 Mar:59:119-26. doi: 10.1016/j.mcn.2014.02.004. Epub 2014 Feb 15.

Abstract

Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory.

Keywords: Blast neurotrauma; Glia; Myo-inositol; Prefrontal cortex; Working memory.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Betaine / metabolism
  • Blast Injuries / metabolism
  • Blast Injuries / physiopathology*
  • Brain Injuries / metabolism
  • Brain Injuries / physiopathology*
  • Creatine / metabolism
  • Ethanolamines / metabolism
  • Glutamic Acid / metabolism
  • Glycerylphosphorylcholine / metabolism
  • Inositol / metabolism*
  • Lactic Acid / metabolism
  • Male
  • Memory, Short-Term*
  • Pattern Recognition, Physiological
  • Prefrontal Cortex / injuries
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Ethanolamines
  • Lactic Acid
  • Glutamic Acid
  • Betaine
  • Inositol
  • gamma-Aminobutyric Acid
  • Glycerylphosphorylcholine
  • phosphorylethanolamine
  • Creatine