A closed-head, rotational traumatic brain injury model demonstrates deficits in righting reflex, neurological function, and auditory brainstem responses in rats.

Abstract

Aims: The pathophysiology of traumatic brain injury (TBI) is incompletely understood and warrants further investigation with preclinical models that recapitulate aspects of the human condition. Therefore, our goal was to quantify the initial presentation of deficits in a closed-head rotational TBI model in male and female rats in return of righting reflex (RORR) and global neurological function including gross sound reflex scores as a measure of acoustic startle.

Methods: A total of 116 rats (43 female) were included in this study that underwent TBI (n = 53), Sham (n = 42), or No Anesthesia control (n = 21) procedures to assess RORR, the Revised Neurobehavioral Severity Scale (NSS-R), or Auditory Brainstem Responses (ABR).

Results: TBI rats had a trend toward a prolonged RORR, which was significantly increased in the TBI compared to control group when normalized to the duration of anesthesia. Gross neurological function was impaired in TBI rats, such that descriptively the largest component was due to acoustic startle deficits. These deficits were not explained by worse (higher) hearing thresholds in auditory brainstem responses, although TBI rats had increased thresholds at 16 and 20 kHz, and a trend at 10 kHz compared to Shams on post-TBI day 1 that was not different by day 8.

Conclusions: This model reproduces acoustic startle, and hearing impairment aspects of human TBI that influence quality of life. Additional studies are necessary to integrate variables from new clinical classification systems including blood-based and imaging biomarkers to aid in the translation to improve patient-oriented outcomes.