Neurons in Subcortical Oculomotor Regions are Vulnerable to Plasma Membrane Damage after Repetitive Diffuse Traumatic Brain Injury in Swine
- 1 September 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 37 (17), 1918-1932
- https://doi.org/10.1089/neu.2019.6738
Abstract
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.This publication has 62 references indexed in Scilit:
- Mechanisms of TBI and Visual Consequences in Military and Veteran PopulationsOptometry and Vision Science, 2013
- Trauma-Induced Plasmalemma Disruptions in Three-Dimensional Neural Cultures Are Dependent on Strain Modality and RateJournal of Neurotrauma, 2011
- Dynamic Changes in Neural Circuit Topology Following Mild Mechanical Injury In VitroAnnals of Biomedical Engineering, 2011
- Mild Traumatic Brain Injury and Diffuse Axonal Injury in SwineJournal of Neurotrauma, 2011
- Traumatic Axonal Injury in the Optic Nerve: Evidence for Axonal Swelling, Disconnection, Dieback, and ReorganizationJournal of Neurotrauma, 2011
- Different Strokes for Different Folks: The Rich Diversity of Animal Models of Focal Cerebral IschemiaJournal of Cerebral Blood Flow & Metabolism, 2010
- Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head InjuryJournal of Neuropathology and Experimental Neurology, 2009
- Acute Plasmalemma Permeability and Protracted Clearance of Injured Cells after Controlled Cortical Impact in MiceJournal of Cerebral Blood Flow & Metabolism, 2007
- Early reduction of NeuN antigenicity induced by soman poisoning in mice can be used to predict delayed neuronal degeneration in the hippocampusNeuroscience Letters, 2006
- An In Vitro Model of Traumatic Neuronal Injury: Loading Rate-Dependent Changes in Acute Cytosolic Calcium and Lactate Dehydrogenase ReleaseJournal of Neurotrauma, 1997