title: Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.
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.
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA.
authors.forename: Venkata Siva Sai Sujith
authors.initials: VS
authors.lastname: Sajja
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit MI.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Perrine
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit MI; Department of Anesthesiology, Wayne State University School of Medicine, Detroit MI.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ghoddoussi
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Hall
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit MI; Department of Anesthesiology, Wayne State University School of Medicine, Detroit MI.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Galloway
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA; Salem VA Medical Center, Research & Development Service, Salem, VA, USA. Electronic address: pvord@vt.edu.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: VandeVord
mesh_terms: D000818:Animals; D001622:Betaine / Q000378:metabolism; D001753:Blast Injuries / Q000378:metabolism / Q000503:physiopathology*; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D003401:Creatine / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D007294:Inositol / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term; D046709:Pattern Recognition, Physiological; D017397:Prefrontal Cortex / Q000293:injuries / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D004983:Ethanolamines; D019344:Lactic Acid; D018698:Glutamic Acid; D001622:Betaine; D007294:Inositol; D005680:gamma-Aminobutyric Acid; D005997:Glycerylphosphorylcholine; C005448:phosphorylethanolamine; D003401:Creatine
keywords: Blast neurotrauma; Glia; Myo-inositol; Prefrontal cortex; Working memory