Journal of neurotrauma
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Journal of neurotrauma · Jun 2012
Clinical TrialCO(2)-Dependent vasomotor reactivity of cerebral arteries in patients with severe traumatic brain injury: time course and effect of augmentation of cardiac output with dobutamine.
Failing cerebral blood flow (CBF) autoregulation may contribute to cerebral damage after traumatic brain injury (TBI). The purpose of this study was to describe the time course of CO(2)-dependent vasoreactivity, measured as CBF velocity in response to hyperventilation (vasomotor reactivity [VMR] index). We included 13 patients who had had severe TBI, 8 of whom received norepinephrine (NE) based on clinical indication. ⋯ Cardiac output and mean CBF velocity increased significantly during dobutamine administration, but VMR index did not change significantly. In conclusion, CO(2) vasomotor reactivity was abnormal in the first 24 h after TBI in most of the patients, but recovered within 48 h in those patients who did not receive NE, in contrast to those eventually receiving the drug. Addition of dobutamine to NE had variable but overall insignificant effects on CO(2) vasomotor reactivity.
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Journal of neurotrauma · Jun 2012
Experimental syringohydromyelia induced by adhesive arachnoiditis in the rabbit: changes in the blood-spinal cord barrier, neuroinflammatory foci, and syrinx formation.
There are many histological examinations of syringohydromyelia in the literature. However, there has been very little experimental work on blood permeability in the spinal cord vessels and ultrastructural changes. We prepared an animal model of spinal adhesive arachnoiditis by injecting kaolin into the subarachnoid space at the eighth thoracic vertebra of rabbits. ⋯ The dilated perivascular spaces indicate alterations of fluid exchange between the subarachnoid and extracellular spaces. Syringomyelia revealed that nerve fibers and nerve cells were exposed on the surface of the syrinx, and necrotic tissue was removed by macrophages to leave a syrinx. Both pathologies differ in their mechanism of development: hydromyelia is attributed to disturbed reflux of cerebrospinal fluid, while tissue necrosis due to disturbed intramedullary blood flow is considered to be involved in formation of the syrinx in syringomyelia.
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Journal of neurotrauma · Jun 2012
tPA-S481A prevents neurotoxicity of endogenous tPA in traumatic brain injury.
Traumatic brain injury (TBI) is associated with loss of autoregulation due to impaired responsiveness to cerebrovascular dilator stimuli, which leads to cerebral hypoperfusion and neuronal impairment or death. Upregulation of tissue plasminogen activator (tPA) post-TBI exacerbates loss of cerebral autoregulation and NMDA-receptor-mediated impairment of cerebral hemodynamics, and enhances excitotoxic neuronal death. However, the relationship between NMDA-receptor activation, loss of autoregulation, and neurological dysfunction is unclear. ⋯ Lateral fluid percussion brain injury was produced in anesthetized piglets. Pial artery reactivity was measured via a closed cranial window, and cerebrospinal fluid (CSF) extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) was quantified by enzyme-linked immunosorbent assay (ELISA). tPA-S481A prevented impairment of cerebral autoregulation and reduced histopathologic changes after TBI by inhibiting upregulation of the ERK isoform of MAPK. Treatment with this tPA variant provides a novel approach for limiting neuronal toxicity caused by untoward NMDA-receptor activation mediated by increased tPA and glutamate following TBI.
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Journal of neurotrauma · Jun 2012
Lateralized response of dynorphin a peptide levels after traumatic brain injury.
Traumatic brain injury (TBI) induces a cascade of primary and secondary events resulting in impairment of neuronal networks that eventually determines clinical outcome. The dynorphins, endogenous opioid peptides, have been implicated in secondary injury and neurodegeneration in rodent and human brain. To gain insight into the role of dynorphins in the brain's response to trauma, we analyzed short-term (1-day) and long-term (7-day) changes in dynorphin A (Dyn A) levels in the frontal cortex, hippocampus, and striatum, induced by unilateral left-side or right-side cortical TBI in mice. ⋯ In naive animals, Dyn A was symmetrically distributed between the two hemispheres. Thus, trauma may reveal a lateralization in the mechanism mediating the response of Dyn A-expressing neuronal networks in the brain. These networks may differentially mediate effects of left and right brain injury on lateralized brain functions.
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Journal of neurotrauma · Jun 2012
Endothelial progenitor cells promote astrogliosis following spinal cord injury through Jagged1-dependent Notch signaling.
Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. ⋯ Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.