Pupillary Light Response Deficits in 4-Week-Old Piglets and Adolescent Children after Low-Velocity Head Rotations and Sports-Related Concussions.

Neurological disorders and traumatic brain injury (TBI) are among the leading causes of death and disability. The pupillary light reflex (PLR) is an emerging diagnostic tool for concussion in humans. We compared PLR obtained with a commercially available pupillometer in the 4 week old piglet model of the adolescent brain subject to rapid nonimpact head rotation (RNR), and in human adolescents with and without sports-related concussion (SRC). The 95% PLR reference ranges (RR, for maximum and minimum pupil diameter, latency, and average and peak constriction velocities) were established in healthy piglets (N = 13), and response reliability was validated in nine additional healthy piglets. PLR assessments were obtained in female piglets allocated to anesthetized sham (N = 10), single (sRNR, N = 13), and repeated (rRNR, N = 14) sagittal low-velocity RNR at pre-injury, as well as days 1, 4, and 7 post injury, and evaluated against RRs. In parallel, we established human PLR RRs in healthy adolescents (both sexes, N = 167) and compared healthy PLR to values obtained <28 days from a SRC (N = 177). In piglets, maximum and minimum diameter deficits were greater in rRNR than sRNR. Alterations peaked on day 1 post sRNR and rRNR, and remained altered at day 4 and 7. In SRC adolescents, the proportion of adolescents within the RR was significantly lower for maximum pupil diameter only (85.8%). We show that PLR deficits may persist in humans and piglets after low-velocity head rotations. Differences in timing of assessment after injury, developmental response to injury, and the number and magnitude of impacts may contribute to the differences observed between species. We conclude that PLR is a feasible, quantifiable involuntary physiological metric of neurological dysfunction in pigs, as well as humans. Healthy PLR porcine and human reference ranges established can be used for neurofunctional assessments after TBI or hypoxic exposures (e.g., stroke, apnea, or cardiac arrest).

Multiple Head Rotations Result in Persistent Gait Alterations in Piglets.

Multiple/repeated mild traumatic brain injury (mTBI) in young children can cause long-term gait impairments and affect the developmental course of motor control. Using our swine model for mTBI in young children, our aim was to (i) establish a reference range (RR) for each parameter to validate injury and track recovery, and (ii) evaluate changes in gait patterns following a single and multiple (5×) sagittal rapid non-impact head rotation (RNR). Gait patterns were studied in four groups of 4-week-old Yorkshire swine: healthy (n = 18), anesthesia-only sham (n = 8), single RNR injury (n = 12) and multiple RNR injury (n = 11). Results were evaluated pre-injury and at 1, 4, and 7 days post-injury. RR reliability was validated using additional healthy animals (n = 6). Repeated mTBI produced significant increases in gait time, cycle time, and stance time, as well as decreases in gait velocity and cadence, on Day One post-injury compared to pre-injury, and these remained significantly altered at Day Four and Day Seven post-injury. The gait metrics of the repeated TBI group also significantly fell outside the healthy RR on Day One, with some recovery by Day Four, while many remained altered at Day Seven. Only a bilateral decrease in hind stride length was observed at Day Four in our single RNR group compared to pre-injury. In sum, repeated and single sagittal TBI can significantly impair motor performance, and gait metrics can serve as reliable, objective, quantitative functional assessments in a juvenile porcine RNR TBI model.