Journal of neurotrauma
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Journal of neurotrauma · Aug 2014
Therapeutic Effects of Pharmacologically induced Hypothermia against Traumatic Brain Injury in Mice.
Preclinical and clinical studies have shown therapeutic potential of mild-to-moderate hypothermia for treatments of stroke and traumatic brain injury (TBI). Physical cooling in humans, however, is usually slow, cumbersome, and necessitates sedation that prevents early application in clinical settings and causes several side effects. Our recent study showed that pharmacologically induced hypothermia (PIH) using a novel neurotensin receptor 1 (NTR1) agonist, HPI-201 (also known as ABS-201), is efficient and effective in inducing therapeutic hypothermia and protecting the brain from ischemic and hemorrhagic stroke in mice. ⋯ HPI-363 decreased the mRNA expression of tumor necrosis factor-α and interleukin-1β (IL-1β), but increased IL-6 and IL-10 levels. Compared with TBI control mice, HPI-363 treatments improved sensorimotor functional recovery after TBI. These findings suggest that the second generation NTR-1 agonists, such as HPI-363, are efficient hypothermic-inducing compounds that have a strong potential in the management of TBI.
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Journal of neurotrauma · Aug 2014
Risk factors for posttraumatic massive cerebral infarction secondary to space-occupying epidural haematoma.
Post-traumatic massive cerebral infarction (MCI) is a fatal complication of concurrent epidural hematoma (EDH) and brain herniation that commonly requires an aggressive decompressive craniectomy. The risk factors and surgical indications of MCI have not been fully elucidated. In this retrospective study, post-traumatic MCI was diagnosed in 32 of 176 patients. ⋯ Incidence of post-traumatic MCI increased from 16.4% in those having any two of the six risk factors to 47.7% in those having any three or more of the six risk factors (p<0.001). Patients with concurrent EDH and brain herniation exhibited an increased risk for post-traumatic MCI with the accumulation of several critical clinical factors. Early decompressive craniectomy based on accurate risk estimation is recommended in efforts to improve patient functional outcomes.
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Journal of neurotrauma · Aug 2014
Traumatic Brain Injury Induced Ependymal Ciliary Loss decreases Cerebral Spinal Fluid Flow.
Traumatic brain injury (TBI) afflicts up to 2 million people annually in the United States and is the primary cause of death and disability in young adults and children. Previous TBI studies have focused predominantly on the morphological, biochemical, and functional alterations of gray matter structures, such as the hippocampus. However, little attention has been given to the brain ventricular system, despite the fact that altered ventricular function is known to occur in brain pathologies. ⋯ We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a particle tracking technique, we demonstrate that cerebrospinal fluid flow is diminished, thus potentially negatively affecting waste and nutrient exchange. Interestingly, injury-induced ventricular system pathology resolves completely by 30 days after injury as ependymal cell ciliogenesis restores cilia density to uninjured levels in the affected lateral ventricle.
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Journal of neurotrauma · Aug 2014
Eotaxin-3 activates Smad through the TGF-β1 pathway in chronic subdural hematoma outer membranes.
Chronic subdural hematoma (CSDH) is considered to be an inflammatory disease. Eosinophils are frequently expressed in the outer membrane of CSDH and are major sources of transforming growth factor beta (TGF-β). The mothers against decapentaplegic (Smad)-signaling pathway, which is activated by TGF-β, has been shown to be involved with fibrosis. ⋯ Smad3 was shown to be present in fibroblasts. These findings indicate that eotaxin-3 is expressed in CSDH fluid, inducing eosinophils into the outer membrane and resulting in elevation of TGF-β with the Smad pathway activated by TGF-β. These data suggest a potential mechanism for CSDH formation and growth.
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Journal of neurotrauma · Aug 2014
Randomized Controlled TrialEffects of serotonergic medications on locomotor performance in humans with incomplete spinal cord injury.
Incomplete spinal cord injury (iSCI) often results in significant motor impairments that lead to decreased functional mobility. Loss of descending serotonergic (5HT) input to spinal circuits is thought to contribute to motor impairments, with enhanced motor function demonstrated through augmentation of 5HT signaling. However, the presence of spastic motor behaviors in SCI is attributed, in part, to changes in spinal 5HT receptors that augment their activity in the absence of 5HT, although data demonstrating motor effects of 5HT agents that deactivate these receptors are conflicting. ⋯ Results indicate that neither medication led to improvements in locomotion, with a significant decrease in peak overground gait speed observed after 5HT antagonists (from 0.8±0.1 to 0.7±0.1 m/s; p=0.01). Additionally, 5-HT medications had differential effects on EMG activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing flexor activity. Our data therefore suggest that acute manipulation of 5HT signaling, despite changes in muscle activity, does not improve locomotor performance after iSCI.