Oeur Anna, Mull Mackenzie, Riccobono Giancarlo, Arbogast Kristy B, Ciuffreda Kenneth J, Joshi Nabin, Fedonni Daniele, Master Christina L, Margulies Susan S
Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA.
Center for Injury Research and Prevention, Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA.
Biomedicines. 2023 Feb 16;11(2):587. doi: 10.3390/biomedicines11020587.
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).
神经疾病和创伤性脑损伤（TBI）是导致死亡和残疾的主要原因之一。瞳孔对光反射（PLR）是一种新兴的用于诊断人类脑震荡的工具。我们比较了在4周龄仔猪模型（该模型的青少年大脑经受快速非撞击性头部旋转（RNR））以及患有和未患有与运动相关脑震荡（SRC）的人类青少年中，使用市售瞳孔测量仪获得的PLR。在健康仔猪（N = 13）中建立了95%的PLR参考范围（RR，针对最大和最小瞳孔直径、潜伏期以及平均和峰值收缩速度），并在另外9只健康仔猪中验证了反应可靠性。在分配到麻醉假手术组（N = 10）、单次（sRNR，N = 13）和重复（rRNR，N = 14）矢状面低速RNR的雌性仔猪中，在损伤前以及损伤后第1、4和7天进行PLR评估，并与RR进行比较。同时，我们在健康青少年（男女皆有，N = 167）中建立了人类PLR RR，并将健康PLR与在距SRC <28天内获得的值（N = 177）进行比较。在仔猪中，rRNR组的最大和最小直径缺陷大于sRNR组。变化在sRNR和rRNR后第1天达到峰值，并在第4天和第7天仍保持改变。在患有SRC的青少年中，仅最大瞳孔直径在RR范围内的青少年比例显著较低（85.8%）。我们表明，在低速头部旋转后，人类和仔猪中可能会持续存在PLR缺陷。损伤后评估时间的差异、对损伤的发育反应以及撞击的次数和强度可能导致物种间观察到的差异。我们得出结论，PLR是一种可行的、可量化的用于评估猪和人类神经功能障碍的非自愿生理指标。所建立的健康猪和人类PLR参考范围可用于TBI或缺氧暴露（如中风丶呼吸暂停或心脏骤停）后的神经功能评估。
