Relationships between injury kinematics, neurological recovery, and pathology following concussion

Abstract

Mild traumatic brain injury (mTBI) affects millions of individuals annually primarily through falls, traffic collisions, or blunt trauma and can generate symptoms that persist for years. Closed-head rotational loading is the most common cause of mild traumatic brain injury and is defined by a rapid rotational acceleration of brain tissue within an intact skull. Injury kinematics – the mechanical descriptors of injury-inducing motion – explain movement of the head, energy transfer to the brain, and, therefore, determine injury severity. However, the relationship between closed-head rotational injury kinematics – such as angular velocity, angular acceleration, and injury duration – and outcome after mild traumatic brain injury is not completely understood. To address this gap in knowledge, we analyzed archived surgical records of 24 swine experiencing a diffuse closed-head rotational acceleration mild traumatic brain injury against 12 sham animals. Kinematics were contrasted against acute recovery outcomes, specifically apnea time, extubation time, standing time, and recovery duration. Compared to controls, animals experiencing a mild traumatic brain injury were far more likely to have apnea (p < 0.001), shorter time to extubation (p = 0.023), and longer time from extubation to standing (p = 0.006). Using least absolute shrinkage and selection operator (LASSO)-based regressions, kinematic parameters, including maximum negative angular velocity and time from peak angular velocity to maximum angular deceleration, were selected to explain variation in apnea time, standing time, and recovery duration. Simplified linear models employing the least absolute shrinkage and selection operator (LASSO)-selected variables explained a modest degree of variation in apnea time (adjusted R2 = 0.18), standing time (adjusted R2=0.19), and recovery duration (adjusted R2 = 0.27). Neuropathology was correlated with multiple injury kinematics, with maximum angular acceleration exhibiting the strongest correlation (R2 = 0.66). Together, these data suggest the interplay between multiple injury kinematics, including maximum negative angular velocity (immediately preceding cessation of head motion) and time from peak angular velocity to maximum angular deceleration, best explain acute recovery metrics and neuropathology after mild traumatic brain injury in swine. Future experiments that independently manipulate individual kinematic parameters could be instrumental in developing translational diagnostics for clinical mild traumatic brain injury.

Hippocampal Interneuronal Dysfunction and Hyperexcitability in a Porcine Model of Concussion

“…The animal’s head was secured to a padded bite plate under anesthesia and attached to the HYGE device. We utilized a coronal plane of rotation that induces a modest delay in return-of-consciousness post-injury (compared to anesthetized sham animals) and minimal subdural bleeding, but produces patterns of diffuse axonal injury, such as swellings in the form of discrete axonal bulbs and axonal varicosities observed at the roots of the cortical gyri, at the interface of the grey and white matter, and within the deep white matter (Johnson, Stewart et al 2016, Johnson, Weber et al 2018, Grovola, Paleologos et al 2021, Wofford, Grovola et al 2021). To induce a mild injury phenotype (concussion), a single rapid head rotation was performed within a range of rotational velocities (168 – 269 rad/sec, n = 9), with the mean angular peak velocity being 226 ± 13 rad/sec.…”

Sex differences in the extent of acute axonal pathologies after experimental concussion

“…In this study, swine were subjected to precisely controlled coronal rotational injuries that ranged from 253 to 262 rad/s, with no difference between female and male injury group (Table 1 ). Rotational kinematics were recorded using angular velocity transducers (Applied Technology Associates) and calculated as previously noted [ 60 ].…”

“…Preemptive analgesia of sustained release buprenorphine (0.2 mg/kg) was injected subcutaneously post-injury. Following previous description [ 60 ], recovery duration was defined as the time elapsed between extubation of animals and when animals were weight-bearing on all four limbs. Sham animals received all procedures described above except for the head rotation.…”

Neurotrauma Prevention Review: Improving Helmet Design and Implementation

“…Rotational acceleration produces axonal shearing, obstructing axonal function, and causing an accumulation of amyloid-beta precursor protein that peaks after 24—48 h [ 52 – 54 ]. In addition, shearing and mechanical forces produce plasma membrane instability resulting in potassium leakage and neuronal depolarization [ 55 , 56 ]. As a result, the excitatory neurotransmitter glutamate is released and binds NMDA receptors, generating a cycle of potentially neurotoxic hyperexcitation [ 54 , 57 – 59 ].…”