Challenges in the Development of Rodent Models of Mild Traumatic Brain Injury

Abstract

Approximately 75% of traumatic brain injuries (TBI) are classified mild (mTBI). Despite the high frequency of mTBI, it is the least well studied. The prevalence of mTBI among service personnel returning from Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF) and the recent reports of an association between repeated mTBI and the early onset of Alzheimer's and other types of dementias in retired athletes has focused much attention on mTBI. The study of mTBI requires the development and validation of experimental models and one of the most basic requirements for an experimental model is that it replicates important features of the injury or disease in humans. mTBI in humans is associated with acute symptoms such as loss of consciousness and pre- and/or posttraumatic amnesia. In addition, many mTBI patients experience long-term effects of mTBI, including deficits in speed of information processing, attention and concentration, memory acquisition, retention and retrieval, and reasoning and decision-making. Although methods for the diagnosis and evaluation of the acute and chronic effects of mTBI in humans are well established, the same is not the case for rodents, the most widely used animal for TBI studies. Despite the magnitude of the difficulties associated with adapting these methods for experimental mTBI research, they must be surmounted. The identification and testing of treatments for mTBI depends of the development, characterization and validation of reproducible, clinically relevant models of mTBI.

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

“…(1) a short period of posttraumatic apnea <30 sec (recognized as an animal analog to human loss of consciousness,20 (2) a short period of righting reflex <6 min, (3) no sign of skull fractures and (4) no history of major hemorrhage(s) at the time of euthanasia. Moreover, our interinjury interval was 48 h, which is similar to our previous work,13, 19 a temporal window during which the mouse brain is known to be vulnerable to subsequent injuries21 in order to mimic human situations (combat or sports) in which additional injuries are sustained prior to full recovery from the previous injury.…”

Repeated mild traumatic brain injury: potential mechanisms of damage

“…[26][27][28] This review focuses on potential mechanisms of damage underlying the cumulative and chronic effects of repeated "closed-head" mTBI, referring to single mTBI in the context of studies exploring subsequent injuries. For more detailed discussion of single mTBI, the reader is referred to Dewitt et al 29 for review. The importance of using clinically relevant experimental models of mTBI is receiving increasing attention and will be touched upon here (see Xiong et al, 30 Angoa-Pérez et al, 31 Laplaca et al, 32 Namjoshi et al, 33 and Zhang et al 34 for further insights).…”

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

“…Owing to the fact that mild traumatic brain injury (mTBI) is three times more common than moderate and severe brain injury combined 1 , a reliable model of mTBI is needed to facilitate research regarding pathophysiology, neurobiological and behavioural outcomes, and therapeutic strategies. For example, partially due to the limitations of current animal models 2 , in the past decade there have been over 200 failed clinical drug trials for the treatment of TBI 3 .…”