Journal of neurotrauma
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Journal of neurotrauma · Mar 2012
Outcome prediction within twelve hours after severe traumatic brain injury by quantitative cerebral blood flow.
We measured quantitative cortical mantle cerebral blood flow (CBF) by stable xenon computed tomography (CT) within the first 12 h after severe traumatic brain injury (TBI) to determine whether neurologic outcome can be predicted by CBF stratification early after injury. Stable xenon CT was used for quantitative measurement of CBF (mL/100 g/min) in 22 cortical mantle regions stratified as follows: low (0-8), intermediate (9-30), normal (31-70), and hyperemic (>70) in 120 patients suffering severe (Glasgow Coma Scale [GCS] score ≤8) TBI. For each of these CBF strata, percentages of total cortical mantle volume were calculated. ⋯ The binary version of the Marshall CT score was an independent predictor of 6-month outcome, whereas age was not. These results suggest that quantitative cerebral cortical CBF measured within the first 6 and 12 h after TBI predicts 6-month outcome, which may be useful in guiding patient care and identifying patients for randomized clinical trials. A larger multicenter randomized clinical trial is indicated.
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Journal of neurotrauma · Mar 2012
Effects of nicotine administration on striatal dopamine signaling after traumatic brain injury in rats.
Previous studies on the therapeutic potential of agents affecting the dopamine system in traumatic brain injury (TBI) suggest that dopamine dysregulation may have a major role in behavioral deficit after TBI. We have previously identified that TBI reduces striatal dopamine synthesis and release at 7 days post-injury. In order to reverse deficits in the activity of tyrosine hydroxylase and dopamine release following TBI, we administered nicotine by intraperitoneal injection into rats for 7 days. ⋯ There was no effect of nicotine injection on extracellular dopamine metabolite levels, indicating the specificity of nicotine's effect on dopamine synthesis and release. Also, the activation of downstream postsynaptic molecule dopamine and cAMP regulated phosphoprotein 32 (DARPP-32) was assessed by Western blots for DARPP-32 phosphorylated at threonine 34 (pDARPP-32-T34). Injury reduced pDARPP-32-T34 levels, but nicotine treatment of injured animals did not alter pDARPP-32-T34 levels, indicating that postsynaptic dopamine signaling is complex, and the recovery of dopamine release may not be sufficient for the recovery of DARPP-32 activity.
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Journal of neurotrauma · Mar 2012
Spinal cord injury triggers an intrinsic growth-promoting state in nociceptors.
Although most investigations of the mechanisms underlying chronic pain after spinal cord injury (SCI) have examined the central nervous system (CNS), recent studies have shown that nociceptive primary afferent neurons display persistent hyperexcitability and spontaneous activity in their peripheral branches and somata in dorsal root ganglia (DRG) after SCI. This suggests that SCI-induced alterations of primary nociceptors contribute to central sensitization and chronic pain after SCI. Does SCI also promote growth of these neurons' fibers, as has been suggested in some reports? The present study tests the hypothesis that SCI induces an intrinsic growth-promoting state in DRG neurons. ⋯ Elongating growth was also found in neurons immunoreactive to calcitonin gene-related peptide (CGRP), suggesting that some of the neurons exhibiting enhanced neuritic growth were nociceptors. The same measurements made on neurons dissociated 1 month after SCI revealed no evidence of elongating growth, although evidence for accelerated initiation of neurite outgrowth was found. Under certain conditions this transient growth-promoting state in nociceptors might be important for the development of chronic pain and hyperreflexia after SCI.
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Journal of neurotrauma · Mar 2012
Cyclin D1 gene ablation confers neuroprotection in traumatic brain injury.
Cell cycle activation (CCA) is one of the principal secondary injury mechanisms following brain trauma, and it leads to neuronal cell death, microglial activation, and neurological dysfunction. Cyclin D1 (CD1) is a key modulator of CCA and is upregulated in neurons and microglia following traumatic brain injury (TBI). In this study we subjected CD1-wild-type (CD1(+/+)) and knockout (CD1(-/-)) mice to controlled cortical impact (CCI) injury to evaluate the role of CD1 in post-traumatic neurodegeneration and neuroinflammation. ⋯ In contrast, CD1(-/-) mice showed reduced CCA and neurodegeneration at 24 h, as well as improved cognitive function, attenuated hippocampal neuronal cell loss, decreased lesion volume, and cortical microglial activation at 21 days post-injury. These findings indicate that CD1-dependent CCA plays a significant role in the neuroinflammation, progressive neurodegeneration, and related neurological dysfunction resulting from TBI. Our results further substantiate the proposed role of CCA in post-traumatic secondary injury, and suggest that inhibition of CD1 may be a key therapeutic target for TBI.
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Journal of neurotrauma · Mar 2012
Endogenous GFAP-positive neural stem/progenitor cells in the postnatal mouse cortex are activated following traumatic brain injury.
Interest in promoting regeneration of the injured nervous system has recently turned toward the use of endogenous stem cells. Elucidating cues involved in driving these precursor cells out of quiescence following injury, and the signals that drive them toward neuronal and glial lineages, will help to harness these cells for repair. Using a biomechanically validated in vitro organotypic stretch injury model, cortico-hippocampal slices from postnatal mice were cultured and a stretch injury equivalent to a severe traumatic brain injury (TBI) applied. ⋯ Our results indicate that a source of quiescent endogenous stem cells residing in the cortex and subcortical tissue proliferate in vitro following TBI. Moreover, these proliferating cells are multipotent and are derived mostly from GFAP-expressing cells. This raises the possibility of using this endogenous source of stem cells for repair following TBI.