Loss of Consciousness and Righting Reflex Following Traumatic Brain Injury: Predictors of Post-Injury Symptom Development (A Narrative Review)

Abstract

Identifying predictors for individuals vulnerable to the adverse effects of traumatic brain injury (TBI) remains an ongoing research pursuit. This is especially important for patients with mild TBI (mTBI), whose condition is often overlooked. TBI severity in humans is determined by several criteria, including the duration of loss of consciousness (LOC): LOC < 30 min for mTBI and LOC > 30 min for moderate-to-severe TBI. However, in experimental TBI models, there is no standard guideline for assessing the severity of TBI. One commonly used metric is the loss of righting reflex (LRR), a rodent analogue of LOC. However, LRR is highly variable across studies and rodents, making strict numeric cutoffs difficult to define. Instead, LRR may best be used as predictor of symptom development and severity. This review summarizes the current knowledge on the associations between LOC and outcomes after mTBI in humans and between LRR and outcomes after experimental TBI in rodents. In clinical literature, LOC following mTBI is associated with various adverse outcome measures, such as cognitive and memory deficits; psychiatric disorders; physical symptoms; and brain abnormalities associated with the aforementioned impairments. In preclinical studies, longer LRR following TBI is associated with greater motor and sensorimotor impairments; cognitive and memory impairments; peripheral and neuropathology; and physiologic abnormalities. Because of the similarities in associations, LRR in experimental TBI models may serve as a useful proxy for LOC to contribute to the ongoing development of evidence-based personalized treatment strategies for patients sustaining head trauma. Analysis of highly symptomatic rodents may shed light on the biological underpinnings of symptom development after rodent TBI, which may translate to therapeutic targets for mTBI in humans.

p17/C18-ceramide–mediated mitophagy is an endogenous neuroprotective response in preclinical and clinical brain injury

“…The impact energy was obtained by multiplying the mass of the weight (kg) with the gravity force (9.8 m/s 2 ) and the height from where it is launched (0.91 or 0.60 m, respectively), as previously reported ( 31 ). The loss of the righting reflex (loss of consciousness) was evaluated based on the latency of self-righting immediately after the injuries, which correlates with injury severity ( 32 ). The average time elapsed before recovery of the righting reflex was significantly increased in both rmTBI ( P < 0.0001) and rlmTBI ( P < 0.0001) mice, compared with the sham controls (Fig.…”

Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury

“…The time duration for loss of righting reflex (LRR) after injury/sham and discontinuation of anesthesia is comparable to the duration of lost consciousness in TBI patients. 31 LRR was used as an index of injury severity in this study as used before. 32–35 On the first day of injury, LRR was considerably longer (366 ± 53 sec) in rmFPI mice than in shams (138 ± 110; Fig.…”

Disorders of nomenclature

“…Aside from having no connection to DoC, its use as an outcome measure is controversial, and though some studies have included it in their results, high variability observed with LRR has been widely reported. As noted in a recent review comparing the prognostic value of brief loss of consciousness that may occur in human mild TBI versus LRR in rodent studies: “LRR is a highly heterogeneous measure subject to large individual variability, such that two rodents experiencing the same injury with identical parameters may have drastically different LRR.” 8 Independent of the mischaracterization of brief LRR as a model of DoC, the extremely low variability in LRR reported in this paper is another anomaly that calls into question its integrity and reliability (Box 1 ).…”