Journal of neurotrauma
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Journal of neurotrauma · Jan 2018
Alterations in the timing of huperzine-A cerebral pharmacodynamics in the acute traumatic brain injury setting.
Traumatic brain injury (TBI) may affect the pharmacodynamics of centrally acting drugs. Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive measure of cortical gamma-aminobutyric acid (GABA)-mediated cortical inhibition. Huperzine A (HupA) is a naturally occurring acetylcholinesterase inhibitor with newly discovered potent GABA-mediated antiepileptic capacity, which is reliably detected by ppTMS. ⋯ This was consistent with a quadratic trend comparison that projects HupA-mediated cortical inhibition to last longer in injured rats (p = 0.007). We show that 1) cortical GABA-mediated inhibition, as measured by ppTMS, decreases acutely post-TBI, 2) HupA restores lost post-TBI GABA-mediated inhibition, and 3) HupA-mediated enhancement of cortical inhibition is delayed post-TBI. The plausible reasons of the latter include 1) low HupA volume of distribution rendering HupA confined in the intravascular compartment, therefore vulnerable to reduced post-TBI cerebral perfusion, and 2) GABAR dysfunction and increased AChE activity post-TBI.
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Journal of neurotrauma · Jan 2018
Variation in blood transfusion and coagulation management in Traumatic Brain Injury at the Intensive Care Unit: A survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.
Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. ⋯ If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.
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Journal of neurotrauma · Jan 2018
Traumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recovery.
Traumatic brain injury (TBI) induces widespread neuroinflammation and accumulation of microtubule associated protein tau (MAPT): two key pathological features of tauopathies. This study sought to characterize the microglial/macrophage response to TBI in genomic-based MAPT transgenic mice in a Mapt knockout background (called hTau). Two-month-old hTau and age-matched control male and female mice received a single lateral fluid percussion TBI or sham injury. ⋯ A battery of behavioral tests revealed that TBI in hTau mice resulted in compromised use of spatial search strategies to complete a water maze task, despite lack of motor or visual deficits. Collectively, these data indicate that the presence of wild-type human tau alters the microglial/macrophage response to a single TBI, induces delayed, region-specific MAPT pathology, and alters cognitive recovery; however, the causal relationship between these events remains unclear. These results highlight the potential significance of communication between MAPT and microglia/macrophages following TBI, and emphasize the role of neuroinflammation in post-injury recovery.
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Journal of neurotrauma · Jan 2018
Protection against TBI-induced neuronal death with post-treatment with a selective calpain-2 inhibitor in mice.
Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. The calcium-dependent protease, calpain, has been shown to be involved in TBI-induced neuronal death. However, whereas various calpain inhibitors have been tested in several animal models of TBI, there has not been any clinical trial testing the efficacy of calpain inhibitors in human TBI. ⋯ Calpain-1 KO enhanced cell death, whereas calpain-2 activity correlated with the extent of cell death, suggesting that calpain-1 activation suppresses and calpain-2 activation promotes cell death following TBI. Systemic injection(s) of a calpain-2 selective inhibitor, NA101, at 1 h or 4 h after CCI significantly reduced calpain-2 activity and cell death around the impact site, reduced the lesion volume, and promoted motor and learning function recovery after TBI. Our data indicate that calpain-1 activity is neuroprotective and calpain-2 activity is neurodegenerative after TBI, and that a selective calpain-2 inhibitor can reduce TBI-induced cell death.
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Journal of neurotrauma · Jan 2018
Increased binding potential of brain adenosine A1 receptor in chronic stages of patients with diffuse axonal injury measured with [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine PET imaging.
The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. ⋯ The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.