Articles: traumatic-brain-injuries.
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Molecular neurobiology · Dec 2016
Traumatic Brain Injury Increases the Expression of Nos1, Aβ Clearance, and Epileptogenesis in APP/PS1 Mouse Model of Alzheimer's Disease.
To test the hypothesis that an amyloidogenic genetic background predisposes to worsening of post-TBI outcome, we investigated whether traumatic brain injury (TBI) in amyloid precursor protein (APP)/PS1 mice aggravates epileptogenesis and/or enhances somatomotor and cognitive impairment. To elaborate the mechanisms of worsening outcomes, we studied changes in the expression of genes involved in APP processing and Tau pathways in the perilesional cortex, ipsilateral thalamus, and ipsilateral hippocampus 16 weeks post-TBI. Mild (mTBI) or severe TBI (sTBI) was triggered using controlled cortical impact in 3-month-old APP/PS1 mice and wild-type (Wt) littermates. ⋯ Motor impairment correlated (p < 0.001) with the increased cortical expression of genes encoding proteins related to β-amyloid (Aβ) clearance, including Clu (r = 0.83), Abca1 (r = 0.78), A2m (r = 0.76), Apoe (r = 0.70), and Ctsd (r = 0.63). Immunohistochemical analysis revealed a focal reduction in Aβ load lateral to lesion core in APP/PS1-sTBI mice compared to APP/PS1-sham mice (p < 0.05). The present study provides the first comprehensive evidence of exacerbated epileptogenesis and its molecular mechanisms in Alzheimer's disease (AD)-related genetic background after TBI.
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J Trauma Acute Care Surg · Dec 2016
Early resuscitation with lyophilized plasma provides equal neuroprotection compared with fresh frozen plasma in a large animal survival model of traumatic brain injury and hemorrhagic shock.
Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is highly lethal. In previous models of combined TBI + HS, we showed that early resuscitation with fresh frozen plasma (FFP) improves neurologic outcomes. Delivering FFP, however, in austere environments is difficult. Lyophilized plasma (LP) is a logistically superior alternative to FFP, but data are limited regarding its efficacy for treatment of TBI. We conducted this study to determine the safety and long-term outcomes of early treatment with LP in a large animal model of TBI + HS. ⋯ Early treatment with LP in TBI + HS is safe and provides neuroprotection that is comparable to FFP.
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Molecular neurobiology · Dec 2016
bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury.
Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced blood-brain barrier (BBB) breakdown. Exogenous basic fibroblast growth factor (bFGF) has been shown to have neuroprotective function in brain injury. The present study therefore investigates the beneficial effects of bFGF on the BBB after TBI and the underlying mechanisms. ⋯ Both the in vivo and in vitro effects are related to the activation of the downstream signaling pathway, PI3K/Akt/Rac-1. Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors LY294002 or si-Rac-1, respectively, partially reduces the protective effect of bFGF on BBB integrity. Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the TBI model and OGD-induced HBMECs injury, and that activation of the PI3K/Akt /Rac-1 signaling pathway underlies these effects.
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Although mild traumatic brain injury (mTBI) comprises 80% of all TBI, the morphological examination of the orbitofrontal cortex (OFC) in relation to clinical symptoms such as aggression, anxiety and depression in a strictly mTBI sample has never before been performed. ⋯ This study found increased aggression, anxiety, and depression, in the mTBI group as well as evidence of cortical thinning in the right lateral OFC. The association between clinical symptoms and the number of mTBI with loss of consciousness suggests the number and severity of mTBI may influence clinical symptoms long after injury. Future studies examining other brain regions involved in the production and regulation of affective processes and inclusion of subjects with well-characterized mood disorders could further elucidate the relationship between mTBI, brain morphology, and clinical symptoms.
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Bedside monitoring of cerebral blood flow (CBF) may provide new insights into the pathophysiology of brain injury, allow early detection of secondary ischemia, and help guide therapy. ⋯ CBF, cerebral blood flowCBV, cerebral blood volumeICG, indocyanine greenICP, intracranial pressureMAP, mean arterial pressuremttICG, mean transit time of indocyanine greenNIRS, near-infrared spectroscopy.