A Novel Histological Technique to Assess Severity of Traumatic Brain Injury in Rodents: Comparisons to Neuroimaging and Neurological Outcomes

Abstract

Here we evaluate an alternative protocol to histologically examine blood-brain barrier (BBB) breakdown, brain edema, and lesion volume following traumatic brain injury (TBI) in the same set of rodent brain samples. We further compare this novel histological technique to measurements determined by magnetic resonance imaging (MRI) and a neurological severity score (NSS). Sixty-six rats were randomly assigned to a sham-operated, mild TBI, moderate TBI, or severe TBI group. 48 h after TBI, NSS, MRI and histological techniques were performed to measure TBI severity outcome. Both the histological and MRI techniques were able to detect measurements of severity outcome, but histologically determined outcomes were more sensitive. The two most sensitive techniques for determining the degree of injury following TBI were NSS and histologically determined BBB breakdown. Our results demonstrate that BBB breakdown, brain edema, and lesion volume following TBI can be accurately measured by histological evaluation of the same set of brain samples.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment

“…TBI was performed, as previously described [ 40 – 43 ]. Rats received inhaled isoflurane as anesthetic with 5% for induction and 1.5–2.5% for maintenance, with equal amounts of medical air and oxygen.…”

“…Two blinded observers calculated NSS, as previously described [ 43 , 45 – 48 ]. Points were assigned for motor function and behavioral changes for an overall score between 0, which represented an intact neurological state, and 25, for the highest neurological impairment.…”

“…MRI was utilized for T2 and diffusion-weighted imaging at 72 h following TBI, as described previously [ 43 ]. A 3 T MRI was used (Ingenia, Philips Medical Systems, Best, The Netherlands) using an eight-channel receive-only coil.…”

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model

“…Traumatic brain injury was performed, as previously described ( Jones et al, 2008 ; Kabadi et al, 2010 ; Frank et al, 2021a , b ). Rats received inhaled isoflurane as anesthetic with 5% for induction and 1.5–2.5% for maintenance, with equal parts medical air and oxygen.…”

“…Two blinded observers calculated Neurological Severity Score (NSS), as previously described ( Boyko et al, 2011a , 2013a ; Ohayon et al, 2012 ; Zlotnik et al, 2012a ; Frank et al, 2021b ). Points were assigned for motor function and behavioral changes for an overall score between 0, indicating an intact neurological state, and 25, representing highest neurological impairment.…”