Journal of neurotrauma
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Journal of neurotrauma · Sep 2012
Comparative StudyOpinions on the preclinical evaluation of novel therapies for spinal cord injury: a comparison between researchers and spinal cord-injured individuals.
We previously conducted a survey to gather the opinions and perspectives of scientific and clinical researchers on what levels of preclinical evidence were needed to justify translating a promising neuroprotective or neuroregenerative therapy in spinal cord injury (SCI) into a human clinical trial (Kwon et al., 2010 ). Here we conducted an analogous survey of individuals living with SCI in which we gathered their expectations for the levels of preclinical evidence achieved by researchers in substantiating the neuroprotective and neuroregenerative therapies being offered to them in clinical trials. In total, 214 individuals with SCI completed the survey, and their responses were compared to the responses of the 235 scientists and clinicians who completed our previous survey. ⋯ SCI individuals also reported strong support for independent replication studies. In general, individuals with SCI had high expectations for the levels of preclinical evidence required to justify translating novel therapies into clinical trials. These expectations should be considered in the decisions to translate specific experimental therapies for SCI.
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Journal of neurotrauma · Sep 2012
Involvement of mitogen-activated protein kinase pathways in expression of the water channel protein aquaporin-4 after ischemia in rat cortical astrocytes.
Brain edema after ischemic brain injury is a key determinant of morbidity and mortality. Aquaporin-4 (AQP4) plays an important role in water transport in the central nervous system and is highly expressed in brain astrocytes. However, the AQP4 regulatory mechanisms are poorly understood. ⋯ Treatment with SB203580, a selective p38 MAPK inhibitor, or SP600125, a selective c-Jun N-terminal kinase inhibitor, significantly attenuated the return of AQP4 to its normal level, and SB203580, but not SP600125, significantly decreased cell death. In an in vivo study, AQP4 expression was upregulated 1-3 days after reperfusion, which was consistent with the time course of p38 phosphorylation and activation, and decreased by the p38 inhibition after transient middle cerebral artery occlusion (MCAO). These results suggest that p38 MAPK may regulate AQP4 expression in cortical astrocytes after ischemic injury.
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Journal of neurotrauma · Sep 2012
Dynamics of rabbit brain edema in focal lesion and perilesion area after traumatic brain injury: a MRI study.
To understand the dynamics of brain edema in different areas after traumatic brain injury (TBI) in rabbit, we used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) to monitor blood-brain barrier (BBB) permeability and cytotoxic brain edema after weight drop-induced TBI in rabbit. The dynamics of BBB permeability and brain edema were quantified using K(trans) and apparent diffusion coefficient (ADC) in the focal and perifocal lesion areas, as well as the area contralateral to the lesion. In the focal lesion area, K(trans) began to increase at 3 h post-TBI, peaked at 3 days, and decreased gradually while remaining higher than sham injury animals at 7 and 30 days. ⋯ Specifically cytotoxic edema was predominant in the focal lesion area while vasogenic edema predominated in the perifocal area in acute phase. Furthermore, secondary opening of the BBB after TBI may appear if secondary injury is not controlled. BBB damage may be a driving force for cytotoxic brain edema and could be a new target for TBI intervention.
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Journal of neurotrauma · Sep 2012
Combination of temperature-sensitive stem cells and mild hypothermia: a new potential therapy for severe traumatic brain injury.
Stem cell transplantation holds great potential for the treatment of traumatic brain injury (TBI). However, the micro-environment of reduced oxygen and accumulated toxins leads to low survival rates of grafted cells, which dramatically limits their clinical application. Mild hypothermia has been demonstrated to improve the micro-environment after severe TBI. ⋯ We found that, compared with UCSMC or tsUCSMC treatment alone, their combination with hypothermia could significantly improve motor and cognitive function with more survival of the grafted cells. Furthermore, we observed that combined therapy with hypothermia and tsUCSMCs exerted the most protective effect on the recovery of neurological function of all the tested treatments, with the highest survival and proliferation rates, and the lowest apoptosis rate. Thus this may represent a new therapeutic strategy for the treatment of severe TBI.