Multiple Head Rotations Result in Persistent Gait Alterations in Piglets

Abstract

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.

Altered Auditory and Visual Evoked Potentials following Single and Repeated Low-Velocity Head Rotations in 4-Week-Old Swine

“…Auditory and visually evoked potentials were captured using methods published previously in healthy piglets [46,47] on each animal before head rotations, to establish a pre-injury baseline, and again at 1, 4, and 7 days after to examine the acute time-course of mild TBI on stimulus processing. Other neurofunctional measures were also collected using this experimental injury paradigm and include piglet gait and pupillary light reflexes, using previously published methods [48,49].…”

“…The 8 min interval between impacts for the repeated RNR group was determined from the same high-school soccer heading data, where girls and boys received 4 and 6 impacts per h, respectively, where impacts were spaced 8 min apart for both sexes. Further details on the determination of piglet head rotation magnitudes are described in [48]. EEG measurements were taken on a pre-injury day (D-1), one (D1), four (D4) and seven days (D7) post-injury (Figure 1).…”

Recent insights from non-mammalian models of brain injuries: an emerging literature

“…These rats also experienced deficits in behavior, exhibited anxiety and increased corticosterone levels following rTBI ( 70 ). When piglets experienced one high-level rotational injury versus one high-level rotational injury with four subsequent mid-level rotational injuries administered 8 min apart, the multiple rotation injury group experienced greater gait times 1 day post after injury ( 71 ). Overall, gait patterns were normal in the single rotation group but were abnormal following the additional rotations ( 71 ), suggesting the long-term effect of repeated rotational brain injury on locomotor behavior.…”

“…When piglets experienced one high-level rotational injury versus one high-level rotational injury with four subsequent mid-level rotational injuries administered 8 min apart, the multiple rotation injury group experienced greater gait times 1 day post after injury ( 71 ). Overall, gait patterns were normal in the single rotation group but were abnormal following the additional rotations ( 71 ), suggesting the long-term effect of repeated rotational brain injury on locomotor behavior. Recent studies underscored the accumulating nature of symptoms in adolescents with repeated concussions, with higher symptom scores observed after the second concussion compared to the initial one ( 72 ).…”

Porcine Models of Neurotrauma and Neurological Disorders

“…Oeur et al applied single and repeated low-velocity head rotations in piglets and also gathered data from adolescent humans presenting with concussion, and found that deficits in the pupillary light reflex were altered after injury compared to reference ranges, suggesting that pupillometry could be a valuable tool for neurofunctional assessment [2]. Mull et al reported significant gait alterations in piglets following rotational acceleration that were more severe and longer lasting when multiple rotations were applied, and they also validated reference ranges for assessing gait alterations in piglets [3]. Dr. Oeur and colleagues also investigated auditory and visually evoked potentials following rotational acceleration in piglets, and found that single and repeated injury groups exhibited different alterations to their evoked potential responses [4].…”