Clinical Relevance of Behavior Testing in Animal Models of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with patients often suffering from consequences such as cognitive deficits, social abnormalities, anxiety, depression, pain, and motor dysfunction. Given that these impairments often have a significant impact on the patient's quality of life, a key aim of therapeutic intervention in TBI is to mitigate these effects. Translational strategies to develop such interventions have heavily featured animal models of TBI. To assess the efficacy of interventions in these models, a range of behavioral outcomes are utilized. However, in light of the past translational failures that have plagued the TBI field, the clinical relevance of these preclinical behavioral tests is now being scrutinized. This article will summarize the behavioral consequences of TBI in humans; describe common methods available for testing cognition, social function, motor ability, pain, as well as depression-and anxiety-like behaviors in animal models of TBI; provide an overview of the results from TBI animal model studies that have utilized these methods; and discuss these pre-clinical behavior methods and findings in terms of their relevance to the clinical TBI setting. We conclude that there is translational value in these methods and their related findings, but also suggest strategies and future research to improve the clinical relevance of behavior testing in animal models of TBI.

The Neurobehavioral Effects of Buprenorphine and Meloxicam on a Blast-Induced Traumatic Brain Injury Model in the Rat

“…This suggests that the effect of a single dose of meloxicam can preserve motor performance for longer than the duration of action of the drug [12-24 hours (49, 50)]. This acute phase protective effect was attributed to the neuroprotective effects of this NSAID medication, namely, reduction of inflammatory cytokines, free radical synthesis, and altering arachidonic acid metabolism (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). This same protective effect is not seen with buprenorphine, which correlates with a study performed by Santiago et al (36) that showed buprenorphine can be used for post-operative pain alleviation after spinal cord injury without affecting behavioral, physiological, or anatomical parameters in rats (36).…”

“…A rotating pole test was used to assess neurological motor dysfunction in the rats after bTBI, with and without pain medications ( 52 , 53 ). The rotating pole test was performed as described earlier ( 22 ).…”

“…Open field tests are often used to measure locomotor activity and anxiety-like behaviors in rodents ( 53 – 55 ). The rats' ambulatory behavior was measured using a locomotor activity apparatus (Omnitech Electronics, Columbus, OH).…”

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

“…Although sociability deficits occur in Service members with mTBI and in blast-exposed Veterans, preclinical studies addressing this issue are inconclusive ( 39 , 63 ). Shultz et al provides an overview of social interaction testing in the context of TBI, emphasizing the need for increased use of automated tracking capable of detecting social behaviors ( 64 ). Sociability in preclinical studies is measured by the duration of an animal's interaction with an unfamiliar animal of the same species.…”

FGF20 protected against BBB disruption after traumatic brain injury by activating the AKT/GSK3β pathway to upregulate junction protein expression and inhibiting JNK/NFκB-dependent neuroinflammation

“…FGF20 is also associated with 5-HT and depressive symptoms in adults [53]. Notably, some patients experience anhedonia and despair after TBI [54]. We speculated that FGF20 can ameliorate neurological deficits following TBI and that exogenous FGF20 can accelerate skull healing after TBI because of the important role of FGF20 in skull closure observed in developing mice [55].…”