Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective

Abstract

Traumatic brain injury (TBI) is a major worldwide healthcare problem. Despite promising outcomes from many preclinical studies, the failure of several clinical studies to identify effective therapeutic and pharmacological approaches for TBI suggests that methods to improve the translational potential of preclinical studies are highly desirable. Rodent models of TBI are increasingly in demand for preclinical research, particularly for closed head injury (CHI), which mimics the most common type of TBI observed clinically. Although seemingly simple to establish, CHI models are particularly prone to experimental variability. Promisingly, bioengineering-oriented research has advanced our understanding of the nature of the mechanical forces and resulting head and brain motion during TBI. However, many neuroscience-oriented laboratories lack guidance with respect to fundamental biomechanical principles of TBI. Here, we review key historical and current literature that is relevant to the investigation of TBI from clinical, physiological and biomechanical perspectives, and comment on how the current challenges associated with rodent TBI models, particularly those involving CHI, could be improved.

Systematic Review of Traumatic Brain Injury and the Impact of Antioxidant Therapy on Clinical Outcomes

“…The clinical management of acute-phase TBI includes pharmacological and nonpharmacological interventions aiming to stabilize patients and minimize secondary injury (Namjoshi et al, 2013). However, results from multiple randomized controlled trials (RCTs) showed mixed effects of the nonpharmacological interventions such as decompressive craniotomy, hyperosmotic therapy, and hypothermia on clinical outcomes (e.g., mortality and Glasgow Coma Scale scores) of TBI (Lu, Gary, Neimeier, Ward, & Lapane, 2012).…”

Repeated mild traumatic brain injury: potential mechanisms of damage

“…80,81 Mechanical input parameters and subsequent outcomes can be more variable in closed-head models incorporating rotational head movement. 33 However, resulting tissue strains are greater than those produced by the pure translational forces that define open-head models 16,82 and are more reflective of human head movement following impact-related mTBI.…”

“…78 However, significant numbers of degenerating neurons in the hippocampus following the repeated mTBI suggest that a more severe injury was induced. The immunosuppressant FK506 (Tacrolimus) or moderate hypothermia (32)(33) C for 1 h) following 2 impactacceleration mTBIs at a 3-h inter-injury interval significantly attenuates axonal and cerebral microvascular changes by inhibiting calcineurin, free-radical and metabolically mediated cascades. 241 Following 2 closed-head mTBIs incorporating rotational acceleration, given on consecutive days, the liver X receptor agonist GW3965 improves cognition, axonal integrity, and Ab clearance in an Apolipoprotein E (ApoE)-dependent manner.…”

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

“…6,7 Mild TBI leads to a variety of adverse sensory, motor, cognitive, and emotional outcomes. The injury with mild TBI appears to stem from the brain tissue deformation that results from the shockwave transmitted through brain and cerebrospinal fluid (CSF) by the impact force, or from the brain compression-expansion during rapid head acceleration-deceleration, 8 which leads to diffuse axonal injury and subsequent secondary degenerative events. 9 A variety of animal models of TBI have been developed to elucidate the biomechanics, pathophysiology, and/or treatment approaches for TBI.…”

“…9 A variety of animal models of TBI have been developed to elucidate the biomechanics, pathophysiology, and/or treatment approaches for TBI. 8 Some animal models of TBI use lateral fluid percussion or controlled piston impact to the exposed dura, which typically causes brain destruction at the site of impact. These approaches thus model severe penetrating TBI rather than mild TBI.…”