Journal of neurotrauma
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Journal of neurotrauma · Jan 2018
Mild traumatic brain injury reduces spine density of projection neurons in the medial prefrontal cortex and impairs extinction of contextual fear memory.
Epidemiology studies have found that a comorbidity exists between traumatic brain injury (TBI) and stress-related disorders. However, the anatomical and cellular bases for this association is poorly understood. An inability to extinguish the memory of a traumatic event lies at the core of many stress-related disorders. ⋯ The reduction in spine density on layer II/III pyramidal neurons we observed may diminish the efficacy of these neurons to inhibit the output of the central amygdala, thereby reducing the ability of the IL to suppress fear responses after extinction training. Consistent with this, mFPI rats display enhanced freezing behavior during and after extinction training as compared to sham-operated controls, although the ability to form contextual fear memories was not impaired. These results may have implications in stress-related disorders associated with mTBI.
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Journal of neurotrauma · Jan 2018
Minocycline Attenuates High Mobility Group Box 1 Translocation, Microglial Activation, and Thalamic Neurodegeneration after Traumatic Brain Injury in Postnatal Day 17 Rats.
In response to cell injury, the danger signal high mobility group box-1 (HMGB) is released, activating macrophages by binding pattern recognition receptors. We investigated the role of the anti-inflammatory drug minocycline in attenuating HMGB1 translocation, microglial activation, and neuronal injury in a rat model of pediatric traumatic brain injury (TBI). Post-natal day 17 Sprague-Dawley rats underwent moderate-severe controlled cortical impact (CCI). ⋯ Minocycline-treated rats demonstrated delayed motor recovery early after injury but had no injury effect on Morris-water maze whereas vehicle-treated rats performed worse than sham on the final two days of testing (both p < 0.05 vs. vehicle). Minocycline globally attenuated HMGB1 translocation and microglial activation in injured brain in a pediatric TBI model and afforded selective thalamic neuroprotection. The HMGB1 translocation and thalamic injury may represent novel mechanistic and regional therapeutic targets in pediatric TBI.
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Journal of neurotrauma · Jan 2018
Repetitive Mild Closed Head Injury Alters Protein Expression and Dendritic Complexity in a Mouse Model.
Worldwide head injuries are a growing problem. In the United States alone, 1.7 million people suffer a head injury each year. While most of these injuries are mild, head injury sufferers still sustain symptoms that can have major medical and economical impacts. ⋯ We found an increase in TDP-43 protein at 60 days post-injury in the hippocampus and a decrease in autophagy factors three days post-injury. Alterations in dendritic complexity were neuronal subtype and location specific. Measurements of neurotropic factors suggest that an increase in complexity in the cortex may be a consequence of neuronal loss of the less connected neurons.
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Journal of neurotrauma · Jan 2018
Repeat mild traumatic brain injury in adolescent rats increases subsequent β-amyloid pathogenesis.
Single moderate-to-severe traumatic brain injuries (TBIs) may increase subsequent risk for neurodegenerative disease by facilitating β-amyloid (Aβ) deposition. However, the chronic effects on Aβ pathogenesis of repetitive mild TBIs (rTBI), which are common in adolescents and young adults, remain uncertain. We examined the effects of rTBI sustained during adolescence on subsequent deposition of Aβ pathology in a transgenic APP/PS1 rat model. ⋯ These increases in hippocampal Aβ plaque load were driven by increases in both plaque number and size. Similar, though less-pronounced, effects were observed in extrahippocampal regions. Increases in Aβ plaque deposition were observed both ipsilaterally and contralaterally to the injury site and in both males and females. rTBIs sustained in adolescence can increase subsequent deposition of Aβ pathology, and these effects are critically dependent on interinjury interval.
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Journal of neurotrauma · Jan 2018
Primary Blast Causes Delayed Effects without Cell Death in Shell-encased Brain Cell Aggregates.
Previous work in this laboratory used underwater explosive exposures to isolate the effects of shock-induced principle stress without shear on rat brain aggregate cultures. The current study has utilized simulated air blast to expose aggregates in suspension and enclosed within a spherical shell, enabling the examination of a much more complex biomechanical insult. Culture medium-filled spheres were exposed to single pulse overpressures of 15-30 psi (∼6-7 msec duration) and measurements within the sphere at defined sites showed complex and spatially dependent pressure changes. ⋯ The imposition of a spherical shell between the single pulse shock wave and the target brain tissue introduces greatly increased complexity to the insult. This work shows that brain tissue can not only discriminate the nature of the pressure changes it experiences, but that a portion of its response is significantly delayed. These results have mechanistic implications for the study of primary blast-induced TBI and also highlight the importance of rigorously characterizing the actual pressure variations experienced by target tissue in primary blast studies.