Journal of neurotrauma
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Journal of neurotrauma · Oct 2016
Ultrastructure of diaschisis lesions following traumatic brain injury.
We used controlled cortical impact in mice to model human traumatic brain injury (TBI). Local injury was accompanied by distal diaschisis lesions that developed within brain regions anatomically connected to the injured cortex. At 7 days after injury, histochemistry documented broadly distributed lesions, particularly in the contralateral cortex and ipsilateral thalamus and striatum. ⋯ Cell bodies and processes that were silver positive at the light microscopy level showed hydropic disintegration consisting of: loss of nuclear heterochromatin; dilated somal and neuritic processes with a paucity of filaments, tubules, and mitochondria; and increased numbers of electron-dense membranous structures. Importantly the cell membrane itself was still intact 3 weeks after injury. Although the full biochemical nature of these lesions remains to be deciphered, the morphological preservation of damaged neurons and processes raises the question of whether this is a reversible process.
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Journal of neurotrauma · Oct 2016
Minimal traumatic brain injury in mice - PAR-1 and thrombin related changes.
Minimal traumatic brain injury (mTBI) is partially defined by the existence of retrograde amnesia and is associated with microscopic bleeds containing activated coagulation factors. In a previous study, we have found that mTBI immediately releases thrombin-like activity in the brain, which induces amnesia by activating protease-activated receptor 1 (PAR-1) and blocking long-term potentiation (LTP). In the present study, we assessed the effects of mTBI on thrombin and PAR-1 levels in the brain using the same model. ⋯ Interestingly, the late elevation in thrombin-like activity was also associated with elevation of the major central nervous system thrombin inhibitor, protease nexin-1, 72 h post-mTBI (10%; p < 0.005). When thrombin was injected into brain ventricles, an increased sensitivity to seizure-like activity was detected at 72 h post-mTBI. The results are compatible with astrocyte activation post-mTBI resulting in increased thrombin secretion, PAR-1 expression, and seizure sensitivity.
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Journal of neurotrauma · Oct 2016
Minor Functional Deficits in Basic Response Patterns for Reinforcement following Frontal Traumatic Brain Injury in Rats.
Traumatic brain injury (TBI) is a major contributor to numerous psychiatric conditions and chronic behavioral dysfunction. Recent studies in experimental brain injury have begun to adopt operant methodologies to assess these deficits, all of which rely on the process of reinforcement. No studies have directly examined how reinforced behaviors are affected by TBI, however. ⋯ Further, injured rats were specifically impaired at lower response requirements on the progressive ratio. Taken together, these findings indicate that simple reinforced behaviors are mostly unaffected after TBI, except in the case of variable ratio schedules, but the altered performance on the higher-order progressive ratio schedule suggests changes involving motivation or potentially perseveration. These findings validate operant measures of more complex behaviors for brain injury, all of which rely on reinforcement and can be taken into consideration when adapting and developing novel functional assessments.
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Journal of neurotrauma · Oct 2016
Serum Neurofilament Light in American Football Athletes Over the Course of a Season.
Despite being underreported, American football boasts the highest incidence of concussion among all team sports, likely due to exposure to head impacts that vary in number and magnitude over the season. This study compared a biological marker of head trauma in American football athletes with non-contact sport athletes and examined changes over the course of a season. Baseline serum neurofilament light polypeptide (NFL) was measured after 9 weeks of no contact and compared with a non-contact sport. ⋯ Over the course of the season, an increase (effect size [ES] = 1.8; p < 0.001) was observed post-camp relative to baseline (1.52 ± 1.18 pg•mL-1), which remained elevated until conference play, when a second increase was observed (ES = 2.6; p = 0.008) over baseline (4.82 ± 2.64 pg•mL-1). A lack of change in non-starters resulted in substantial differences between starters and non-starters over the course of the season. These data suggest that a season of collegiate American football is associated with elevations in serum NFL, which is indicative of axonal injury, as a result of head impacts.
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Journal of neurotrauma · Oct 2016
Microglial/macrophage polarization dynamics following traumatic brain injury.
Activated microglia and macrophages exert dual beneficial and detrimental roles after central nervous system injury, which are thought to be due to their polarization along a continuum from a classical pro-inflammatory M1-like state to an alternative anti-inflammatory M2-like state. The goal of the present study was to analyze the temporal dynamics of microglia/macrophage polarization within the lesion micro-environment following traumatic brain injury (TBI) using a moderate-level controlled cortical impact (CCI) model in mice. We performed a detailed phenotypic analysis of M1- and M2-like polarized microglia/macrophages, as well as nicotinamide adenine dinucleotide phosphate oxidase (NOX2) expression, through 7 days post-injury using real-time polymerase chain reaction (qPCR), flow cytometry and image analyses. ⋯ In a follow up study, we administered a selective NOX2 inhibitor, gp91ds-tat, to CCI mice starting at 24 h post-injury to investigate the relationship between NOX2 and M1-like/Mtran phenotypes. Delayed gp91ds-tat treatment altered M1-/M2-like balance in favor of the anti-inflammatory M2-like phenotype, and significantly reduced oxidative damage in neurons at 7 days post-injury. Therefore, our data suggest that despite M1-like and M2-like polarized microglia/macrophages being activated after TBI, the early M2-like response becomes dysfunctional over time, resulting in development of pathological M1-like and Mtran phenotypes driven by increased NOX2 activity.