Journal of neurotrauma
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Journal of neurotrauma · Oct 2010
Randomized Controlled TrialEndothelin-1 is increased in cerebrospinal fluid and associated with unfavorable outcomes in children after severe traumatic brain injury.
Severe pediatric traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Hypoperfusion of injured brain tissues after TBI is also associated with unfavorable outcomes. Therapeutic hypothermia is an investigational treatment strategy for use in patients with severe TBI that has shown differential effects on various cerebrospinal fluid (CSF) mediators in pediatric patients. ⋯ ET-1 is increased in children with severe TBI and is associated with unfavorable outcomes. This increase in ET-1 may mediate the hypoperfusion or cerebrovascular dysfunction accompanying severe TBI in children. Importantly, hypothermia does not affect the brain's ET-1 response as measured in the CSF.
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Journal of neurotrauma · Oct 2010
Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.
Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. ⋯ Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.
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Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that exogenous administration of VEGF(165) increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. ⋯ It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI.
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Journal of neurotrauma · Oct 2010
N-acetylcysteine improves hemodynamics and reduces oxidative stress in the brains of newborn piglets with hypoxia-reoxygenation injury.
Reactive oxygen species have been implicated in the pathogenesis of hypoxic-ischemic injury. It has been shown previously that treating an animal with N-acetyl-L-cysteine (NAC), a scavenger of free radicals, significantly minimizes hypoxic-ischemic-induced brain injury in various acute models. Using a subacute swine model of neonatal hypoxia-reoxygenation (H-R), we evaluated the long-term beneficial effect of NAC against oxidative stress-induced brain injury. ⋯ Compared with H-R controls, significantly higher amounts of anesthetic and sedative medications were required to maintain the NAC-treated piglets in stable condition throughout the experimental period, indicating a stronger recovery. Post-resuscitation NAC treatment also significantly attenuated the increase in cortical caspase-3 and lipid hydroperoxide concentrations. Our findings suggest that post-resuscitation administration of NAC reduces cerebral oxidative stress with improved cerebral oxygen delivery, and probably attenuates apoptosis in newborn piglets with H-R insults.
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Journal of neurotrauma · Oct 2010
Injury-induced regulation of steroidogenic gene expression in the cerebellum.
Sex steroids assist adult neural tissue in the protection from and repair of damage resulting from neural injury; some steroids may be synthesized in the brain. Songbirds are especially useful models to explore steroidal neuroprotection and repair. First, the full suite of cholesterol transporters and steroidogenic enzymes are expressed in the zebra finch (ZF) brain. ⋯ Sex differences in response to the lesions were detected for TSPO, StAR, and aromatase. All birds responded to experimental conditions by showing time-dependent changes in the expression of TSPO, SCC, and aromatase, suggesting that acute trauma or stress may impact neurosteroidogensis for many days. These data suggest that the cerebellum is an active site of steroid synthesis in the brain, and each steroidogenic factor likely provides neuroprotection and promotes repair.