Journal of neurotrauma
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Journal of neurotrauma · Nov 2013
Progress in Developing Common Data Elements for Traumatic Brain Injury Research: Version Two- The End of the Beginning.
To accelerate data sharing and research on traumatic brain injury (TBI), several federal agencies have been collaborating to support the development and implementation of common data elements (CDEs). The first recommendations for CDEs were made in 2010, and were well suited for hospital-based studies of acute TBI in adults. To broaden the utility of the TBI CDEs, experts were asked to update the recommendations to make them relevant to all ages, levels of injury severity, and phases of recovery. ⋯ Version 2 provides a rich data dictionary for TBI research with about 900 CDEs. Many of the CDEs overlap across the study types, which will facilitate comparisons and meta-analysis across studies. Further modifications of the CDEs should be based on evaluation of their usefulness following implementation across a range of studies.
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Journal of neurotrauma · Nov 2013
tPA-S(481)A Prevents Impairment of Cerebrovascular Autoregulation by Endogenous tPA after Traumatic Brain Injury by Upregulating p38 MAPK and Inhibiting ET-1.
Traumatic brain injury (TBI) is associated with loss of cerebrovascular autoregulation, which leads to cerebral hypoperfusion. Mitogen activated protein kinase (MAPK) isoforms ERK, p38, and JNK and endothelin-1 (ET-1) are mediators of impaired cerebral hemodynamics after TBI. ⋯ We investigated the ability of variants that lack proteolytic activity but bind/block activation of NMDA-Rs by wt tPA (tPA-S(481)A), do not bind/block activation of NMDA-Rs but are proteolytic (tPA-A(296-299)), or neither bind/block NMDA-Rs nor are proteolytic (tPA-A(296-299)S(481)A) to prevent impairment of autoregulation after TBI and the role of MAPK and ET-1 in such effects. Results show that tPA-S(481)A given 3 h post-TBI, but not tPA-A(296-299) or tPA-A(296-299)S(481)A prevents impaired autoregulation by upregulating p38 and inhibiting ET-1, suggesting that tPA-S(481)A has a realistic therapeutic window and focuses intervention on NMDA-Rs to improve outcome.
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Journal of neurotrauma · Nov 2013
Injury-Induced Expression of Glial Androgen Receptor in the Zebra Finch Brain.
Astrogliosis occurs following injury to the zebra finch brain. To date, only estrogen synthase (aromatase) has been identified in injury-induced astrocytes. The expression of other steroidogenic enzymes or their receptors remains unknown in the avian brain. ⋯ Finches were given a single penetrating injury and brain tissue was collected 24 or 72 h later. Expression of androgen receptor was examined using immunohistochemistry and quantified using quantitative polymerase chain reaction (qPCR) analysis. Androgen receptors were localized to astrocytes versus neurons, further solidifying the role for astrocytes in neural recovery.
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Journal of neurotrauma · Nov 2013
Comparative StudyImpact of Moderate Blast Exposures on Thrombin Biomarkers Assessed by Calibrated Automated Thrombography in Rats.
Severe blast exposures are frequently complicated with fatal intracranial hemorrhages. However, many more sustain low level blasts without tissue damage detectable by brain imaging. To investigate effects of nonlethal blast on thrombin-related biomarkers, rats were subjected to two different types of head-directed blast: 1) moderate "composite" blast with strong head acceleration or 2) moderate primary blast, without head acceleration. ⋯ The changes were also observed in other microvascular/inflammatory/hemostatic biomarkers. Integrin α/β and sICAM-1 levels were elevated after both "composite" and primary blast at 6 h, 1 day, and 7 days. sE-selectin exhibited near normal levels after "composite" blast, but increased significantly at 7 days after primary blast; MMP-2, MMP-8, and MMP-13 slightly rose after "composite" blast and significantly increased (∼2-4-fold) after primary blast. In summary, CAT may have a clinical diagnostic utility in combination with selected set of microvascular/inflammatory biomarkers in patients subjected to low/moderate level blast exposures.
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Journal of neurotrauma · Nov 2013
Cortical murine neurons lacking the neurofilament light chain protein have an attenuated response to injury in vitro.
Neurofilaments (NFs) have been proposed to have a significant role in attempted axonal regeneration following a variety of forms of injury. The NF triplet proteins of the central nervous system are comprised of light (NF-L), medium (NF-M) and heavy (NF-H) chains and are part of the type IV intermediate filament family. We sought to define the role of NF-L in the neuronal response to trauma and regeneration by examining the effect of total absence of the NF-L protein on neuronal maturation and response to axotomy. ⋯ Further, we demonstrate that α-internexin co-immunoprecipitates with the NF binding protein NDel1 in NFL-KO cortical neurons in vitro. Following localized axotomy, NF-L KO neurons demonstrated reduced amyloid precursor protein accumulation in damaged neurites as well as a significant reduction in the number of axons regenerating (4.79+/-0.58 sprouts) in comparison to control preparations (10.47+/-1.11 sprouts) (p<0.05). These studies indicate that NFs comprising NF-L have a dynamic role in the reactive and regenerative changes in axons following injury.