Study of neurometabolic and behavioral alterations in rodent model of mild traumatic brain injury: a pilot study

• Published in: NMR in biomedicine Vol. 29; no. 12; pp. 1748 - 1758
• Main Authors: Singh, Kavita, Trivedi, Richa, Haridas, Seenu, Manda, Kailash, Khushu, Subash
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-12-2016; Wiley Subscription Services, Inc
• Subjects: Animals; Anxiety; Behavior; Behavior, Animal; behavioral study; Biomarkers - metabolism; Brain Concussion - complications; Brain Concussion - physiopathology; cortex; Disease Models, Animal; hippocampus; Hippocampus - metabolism; Humans; Male; Mental Disorders - etiology; Mental Disorders - physiopathology; mild traumatic brain injury; Molecular Imaging - methods; neurometabolic; Pilot Projects; Proton Magnetic Resonance Spectroscopy - methods; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Rodents; Sensitivity and Specificity; spectroscopy; Taurine - metabolism; Traumatic brain injury; cortex; anxiety; neurometabolic; hippocampus; spectroscopy; behavioral study; mild traumatic brain injury
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.3627

Mild traumatic brain injury (mTBI) is the most common form of TBI (70–90%) with consequences of anxiety‐like behavioral alterations in approximately 23% of mTBI cases. This study aimed to assess whether mTBI‐induced anxiety‐like behavior is a consequence of neurometabolic alterations. mTBI was induced using a weight drop model to simulate mild human brain injury in rodents. Based on injury induction and dosage of anesthesia, four animal groups were included in this study: (i) injury with anesthesia (IA); (ii) sham1 (injury only, IO); (iii) sham2 (only anesthesia, OA); and (iv) control rats. After mTBI, proton magnetic resonance spectroscopy (1H‐MRS) and neurobehavioral analysis were performed in these groups. At day 5, reduced taurine (Tau)/total creatine (tCr, creatine and phosphocreatine) levels in cortex were observed in the IA and IO groups relative to the control. These groups showed mTBI‐induced anxiety‐like behavior with normal cognition at day 5 post‐injury. An anxiogenic effect of repeated dosage of anesthesia in OA rats was observed with normal Tau/tCr levels in rat cortex, which requires further examination. In conclusion, this mTBI model closely mimics human concussion injury with anxiety‐like behavior and normal cognition. Reduced cortical Tau levels may provide a putative neurometabolic basis of anxiety‐like behavior following mTBI.
This mild traumatic brain injury (mTBI) model closely mimics human concussion injury with anxiety‐like behavior and normal cognition observed at day 5 using the open field test and novel object recognition test. 1H‐MRS shows reduced cortical taurine levels and normal hippocampal metabolic profile. This model may indicate a putative neurometabolic basis of anxiety‐like behavior following mTBI.