Oculomotor deficits, such as insufficiencies in accommodation, convergence, and saccades, are common following traumatic brain injury (TBI). Previous studies in patients with mild TBI attributed these deficits to insufficient activation of subcortical oculomotor nuclei, although the exact mechanism is unknown. A possible cause for neuronal dysfunction in these regions is biomechanically induced plasma membrane permeability. We used our established porcine model of head rotational TBI to investigate whether cell permeability changes occurred in subcortical oculomotor areas following single or repetitive TBI, with repetitive injuries separated by 15 min, 3 days, or 7 days. Swine were subjected to sham conditions or head rotational acceleration in the sagittal plane using a HYGE pneumatic actuator. Two hours prior to the final injury, the cell-impermeant dye Lucifer Yellow was injected into the ventricles to diffuse throughout the interstitial space to assess plasmalemmal permeability. Animals were sacrificed 15 min after the final injury for immunohistological analysis. Brain regions examined for cell membrane permeability included caudate, substantia nigra pars reticulata, superior colliculus, and cranial nerve oculomotor nuclei. We found that the distribution of permeabilized neurons varied depending on the number and spacing of injuries. Repetitive injuries separated by 15 min or 3 days resulted in the most permeability. Many permeabilized cells lost neuron-specific nuclear protein reactivity, although no neuronal loss occurred acutely after injury. Microglia contacted and appeared to begin phagocytosing permeabilized neurons in repetitively injured animals. These pathologies within oculomotor areas may mediate transient dysfunction and/or degeneration that may contribute to oculomotor deficits following diffuse TBI.

中文翻译：

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皮层下动眼神经区域的神经元在猪重复性弥漫性创伤性脑损伤后容易受到质膜损伤。

外伤性脑损伤 (TBI) 后常见的动眼神经缺陷，例如调节、会聚和眼跳不足。先前对轻度 TBI 患者的研究将这些缺陷归因于皮层下动眼神经核的激活不足，尽管确切机制尚不清楚。这些区域中神经元功能障碍的一个可能原因是生物力学诱导的质膜通透性。我们使用我们建立的头部旋转 TBI 猪模型来研究单次或重复 TBI 后皮层下动眼神经区域是否发生细胞通透性变化，重复损伤间隔 15 分钟、3 天或 7 天。使用 HYGE 气动执行器在矢状面对猪进行假手术或头部旋转加速。在最后一次受伤前两小时，将细胞不可渗透染料 Lucifer Yellow 注入心室以扩散到整个间质空间，以评估质膜渗透性。在最后一次损伤后 15 分钟处死动物进行免疫组织学分析。检查细胞膜通透性的大脑区域包括尾状核、黑质网状部、上丘和颅神经动眼神经核。我们发现透化神经元的分布因损伤的数量和间隔而异。相隔 15 分钟或 3 天的重复损伤导致最大的渗透性。许多透化细胞失去了神经元特异性核蛋白反应性，尽管在损伤后没有发生急性神经元丢失。小胶质细胞接触并似乎开始吞噬反复受伤的动物中的透化神经元。