Journal of neurotrauma
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Journal of neurotrauma · Sep 2018
Long-Term Functional and Structural Consequences of Primary Blast Overpressure to the Eye.
Acoustic blast overpressure (ABO) injury in military personnel and civilians is often accompanied by delayed visual deficits. However, most animal model studies dealing with blast-induced visual defects have focused on short-term (≤1 month) changes. Here, we evaluated long-term (≤8 months) retinal structure and function deficits in rats with ABO injury. ⋯ Age, but not blast exposure, altered Y-maze outcomes. GFAP was greatly increased in blast-exposed retinas. ABO exposure resulted in visual and retinal changes that persisted up to 8 months post-blast, mimicking some of the visual deficits observed in human blast-exposed patients, thereby making this a useful model to study mechanisms of injury and potential treatments.
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Journal of neurotrauma · Sep 2018
Circular Ribonucleic Acid Expression Alteration in Exosomes from the Brain Extracellular Space after Traumatic Brain Injury in Mice.
Traumatic brain injury (TBI) has high morbidity and mortality rates. The mechanisms underlying TBI are unclear and may include the change in biological material in exosomes. Circular ribonucleic acids (circRNAs) are enriched and stable in exosomes, which can function as microRNA (miRNA) sponges to regulate gene expression levels. ⋯ The most highly correlated pathways that we identified were involved primarily with glutamatergic synapse and the cyclic guanosine monophosphate-protein kinase G signaling pathway. The circRNA-miRNA network predicted the potential roles of these differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our study broadens the horizon of research on gene regulation in exosomes from the brain extracellular space after TBI and provides novel targets for further research on both the molecular mechanisms of TBI and the potential intervention therapy targets.
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Journal of neurotrauma · Sep 2018
Selective Vulnerability of the Foramen Magnum in a Rat Blast Traumatic Brain Injury Model.
Primary blast traumatic brain injury (bTBI) accounts for a significant proportion of wartime trauma. Previous studies have demonstrated direct brain injury by blast waves, but the effect of the location of the blast epicenter on the skull with regard to brain injury remains poorly characterized. ⋯ At all blast overpressures studied (668-1880 kPa), rats subjected to FM-bTBI demonstrated strikingly higher mortality, increased durations of both apnea and hypoxia, and increased severity of convexity subdural hematomas, than rats subjected to B-bTBI. Together, these data suggest a unique role for the foramen magnum region in mortality and brain injury following blast exposure, and emphasize the importance of the choice of blast focus location in experimental models of bTBI.
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Journal of neurotrauma · Sep 2018
Memory Deficit in an Object Location Task after Mild Traumatic Brain Injury Is Associated with Impaired Early Object Exploration and Both Are Restored by Branched Chain Amino Acid Dietary Therapy.
The relation between traumatic brain injury (TBI) and memory dysfunction is well established, yet imprecise. Here, we investigate whether mild TBI causes a specific deficit in spatial episodic memory. Fifty-eight (29 TBI, 29 sham) mice were run in a spatial recognition task. ⋯ In addition, the TBI-specific impairment was accompanied by a decrease in exploratory behavior during the first 3 mins of the initial exposure to the test objects. These memory and exploratory behavioral deficits were linked as branched-chain amino acid (BCAA) dietary therapy restored both memory performance and normal exploratory behavior. Our findings 1) support the use of BCAA therapy as a potential treatment for mild TBI and 2) suggest that poor memory performance post-TBI is associated with a deficit in exploratory behavior that is likely to underlie the encoding needed for memory formation.
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Journal of neurotrauma · Sep 2018
FGF21 Protects the Blood-Brain Barrier by Upregulating PPARγ via FGFR1/β-klotho after Traumatic Brain Injury.
Blood-brain barrier (BBB) disruption and dysfunction result in brain edema, which is responsible for more than half of all deaths after severe traumatic brain injury (TBI). Fibroblast growth factor 21 (FGF21) has a potential neuroprotective function in the brain. However, the effects and underlying possible mechanism of action on BBB integrity following TBI remain unknown. ⋯ In addition, the specific FGFR1 and peroxisome proliferator-activated receptor gamma (PPARγ) inhibitors PD173074 and GW9662, respectively, were applied to further explore the possible mechanism of rhFGF21 in BBB maintenance after TBI. rhFGF21 markedly reduced neurofunctional behavior deficits and cerebral edema degree, preserved BBB integrity, and recued brain tissue loss and neuron apoptosis in the mouse model after TBI. Both in vivo and in vitro, rhFGF21 upregulated TJ and AJ proteins, thereby preserving the BBB. Moreover, rhFGF21 activated PPARγ in TNF-α-induced HBMECs through formation of an FGF21/FGFR1/β-klotho complex. rhFGF21 protected the BBB through FGF21/FGFR1/β-klotho complex formation and PPARγ activation, which upregulated TJ and AJ proteins.