Psychosocial impairment following mild blast-induced traumatic brain injury in rats

Nicholas S Race; Katharine D Andrews; Elizabeth A Lungwitz; Sasha M Vega Alvarez; Timothy R Warner; Glen Acosta; Jiayue Cao; Kun-Han Lu; Zhongming Liu; Amy D Dietrich; Sreeparna Majumdar; Anantha Shekhar; William A Truitt; Riyi Shi

doi:10.1016/j.bbr.2021.113405

Psychosocial impairment following mild blast-induced traumatic brain injury in rats

Behav Brain Res. 2021 Aug 27:412:113405. doi: 10.1016/j.bbr.2021.113405. Epub 2021 Jun 23.

Authors

Affiliations

¹ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Medical Scientist Training Program, Indiana University School of Medicine, Indianapolis, IN, USA.
² Medical Scientist Training Program, Indiana University School of Medicine, Indianapolis, IN, USA; Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ PULSe Interdisciplinary Life Science Program, Purdue University, West Lafayette, IN, USA.
⁵ Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Anatomy, Cellular Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶ Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
⁷ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA.
⁸ Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA; School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA.
⁹ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA; School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA.
¹⁰ Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Clinical and Translational Sciences Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
¹¹ Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Anatomy, Cellular Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: btruitt@iu.edu.
¹² Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; PULSe Interdisciplinary Life Science Program, Purdue University, West Lafayette, IN, USA; Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA; Center for Paralysis Research, West Lafayette, IN, USA. Electronic address: riyi@purdue.edu.

Abstract

Traumatic brain injury (TBI) is associated with increased risk for mental health disorders, impacting post-injury quality of life and societal reintegration. TBI is also associated with deficits in psychosocial processing, defined as the cognitive integration of social and emotional behaviors, however little is known about how these deficits manifest and their contributions to post-TBI mental health. In this pre-clinical investigation using rats, a single mild blast TBI (mbTBI) induced impairment of psychosocial processing in the absence of confounding physical polytrauma, post-injury motor deficits, affective abnormalities, or deficits in non-social behavior. Impairment severity correlated with acute upregulations of a known oxidative stress metabolite, 3-hydroxypropylmercapturic acid (3-HPMA), in urine. Resting state fMRI alterations in the acute post-injury period implicated key brain regions known to regulate psychosocial behavior, including orbitofrontal cortex (OFC), which is congruent with our previous report of elevated acrolein, a marker of neurotrauma and 3-HPMA precursor, in this region following mbTBI. OFC of mbTBI-exposed rats demonstrated elevated mRNA expression of metabotropic glutamate receptors 1 and 5 (mGluR1/5) and injection of mGluR1/5-selective agonist in OFC of uninjured rats approximated mbTBI-induced psychosocial processing impairment, demonstrating a novel role for OFC in this psychosocial behavior. Furthermore, OFC may serve as a hotspot for TBI-induced disruption of psychosocial processing and subsequent mental health disorders.

Keywords: Blast; Brain injury; Head trauma; Psychosocial; Safety learning.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / analogs & derivatives
Acetylcysteine / analysis
Acetylcysteine / urine
Acrolein / analysis
Acrolein / metabolism
Animals
Blast Injuries / psychology
Brain / physiopathology
Brain Concussion / physiopathology
Brain Concussion / psychology*
Brain Injuries / psychology
Disease Models, Animal
Magnetic Resonance Imaging
Male
Prefrontal Cortex / metabolism
Prefrontal Cortex / physiopathology*
Psychosocial Functioning*
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / analysis
Receptors, Metabotropic Glutamate / metabolism

Substances

Receptors, Metabotropic Glutamate
Acrolein
S-(3-hydroxypropyl)cysteine N-acetate
Acetylcysteine

Abstract

Publication types

MeSH terms

Substances

Grants and funding