ArticleActa neuropathologica communications2026
Spatial associations between neuronal membrane damage and vasculature after repetitive diffuse TBI in pigs.
Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Closed-head traumatic brain injury (TBI) generally results in diffusely distributed neuropathology. However, factors influencing the micro-scale distribution of this neuropathology remain unknown. Because neurovasculature exhibits different mechanical properties from the surrounding parenchyma, we postulated that these material transitions would increase the likelihood of biophysical damage and resultant neuropathology. Accordingly, we measured the incidence of neuronal plasmalemmal damage in perivascular domains using an established porcine model of single or repetitive closed-head rotational acceleration induced TBI. We found a significant increase in the proportion of regions containing permeabilized neurons in the cortex, thalamus, and midbrain following a single head rotation. We next employed an unbiased sampling methodology that mapped the distribution of vasculature (location, size, and directionality) and permeabilized neurons to determine if neuronal permeability increased based on proximity to vasculature. We identified an increase in the number of permeabilized neurons and a significant decrease in the number of larger (> 100 μm) vessels in the midbrain after repetitive TBI separated by 3 days. Furthermore, we identified that perivascular areas exhibited an increased density of neuronal permeability relative to more distal, extraperivascular spaces but only when excluding blood vessels that had no associations with permeabilized neurons. Neuronal permeability distribution was not affected by vessel size. These data suggest that vascular changes and neuronal damage may be unique consequences based on injury biomechanics, timing between repetitive injuries, and neuroanatomical features. While neuroanatomical features such as distance to the nearest vessel contribute to the distribution of neuronal mechanoporation, our findings indicate that perivascular proximity is a secondary, not primary, factor influencing this distribution. More research is needed to identify other factors that affect the susceptibility and distribution of neuronal plasmalemmal pathology.
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