Journal of neurotrauma
-
Journal of neurotrauma · Oct 2015
Right median nerve electrical stimulation for acute traumatic coma patients.
The right median nerve as a peripheral portal to the central nervous system can be electrically stimulated to help coma arousal after traumatic brain injury (TBI). The present study set out to examine the efficacy and safety of right median nerve electrical stimulation (RMNS) in a cohort of 437 comatose patients after severe TBI from August 2005 to December 2011. The patients were enrolled 2 weeks after their injury and assigned to the RMNS group (n=221) receiving electrical stimulation for 2 weeks or the control group (n = 216) treated by standard management according to the date of birth in the month. ⋯ For persons regaining consciousness, the functional independence measurement (FIM) score was higher among the RMNS group patients (91.45 ± 8.65 vs. 76.23 ± 11.02, p < 0.001). There were no unique complications associated with the RMNS treatment. The current study, although with some limitations, showed that RMNS may serve as an easy, effective, and noninvasive technique to promote the recovery of traumatic coma in the early phase.
-
Journal of neurotrauma · Oct 2015
Neuroenergetic response to prolonged cerebral glucose depletion after severe brain injury and the role of lactate.
Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [<1.0 mmol/L] for at least 2 h) were identified among 26 patients. ⋯ There was a strong correlation between blood and brain lactate when LPR was normal (r = 0.56; p < 0.0001), while an inverse correlation (r = -0.11; p = 0.04) was observed at elevated LPR >25. The correlation between blood and brain glucose also decreased from r = 0.62 to r = 0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.
-
Journal of neurotrauma · Oct 2015
Inhibition of eIF2α phosphatase reduces tissue damage and improves learning and memory following experimental traumatic brain injury.
Patients who survive traumatic brain injury (TBI) are often faced with persistent memory deficits. The hippocampus, a structure critical for learning and memory, is vulnerable to TBI and its dysfunction has been linked to memory impairments. Protein kinase RNA-like ER kinase regulates protein synthesis (by phosphorylation of eukaryotic initiation factor 2 alpha [eIF2α]) in response to endoplasmic reticulum (ER) stressors, such as increases in calcium levels, oxidative damage, and energy/glucose depletion, all of which have been implicated in TBI pathophysiology. ⋯ Moreover, guanabenz treatment attenuated TBI-associated motor, vestibulomotor, recognition memory, and spatial learning and memory dysfunction. Interestingly, when the initiation of treatment was delayed by 24 h, or the dose reduced to 0.5 mg/kg, some of these beneficial effects were still observed. Taken together, these findings further support the involvement of ER stress signaling in TBI pathophysiology and indicate that guanabenz may have translational utility.
-
Journal of neurotrauma · Oct 2015
Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury.
Post-traumatic seizures can exacerbate injurious outcomes of severe brain trauma, yet effective treatments are limited owing to the complexity of the pathology underlying the concomitant occurrence of both events. In this study, we tested C-10068, a novel deuterium-containing analog of (+)-N-methyl-3-ethoxymorphinan, in a rat model of penetrating ballistic-like brain injury (PBBI) and evaluated the effects of C-10068 on PBBI-induced nonconvulsive seizures (NCS), acute neuroinflammation, and neurofunctional outcomes. NCS were detected by electroencephalographic monitoring. ⋯ Further, C-10068 treatment significantly attenuated astrocyte activation in seizure-free animals. However, C-10068 failed to improve PBBI-induced motor and cognitive functions with the dosing regimen used in this study. Overall, the results indicating that C-10068 exerts both potent antiseizure and antiinflammatory effects are promising and warrant further investigation.
-
Journal of neurotrauma · Oct 2015
Pro-Neurotrophin binding to p75 neurotrophin receptor (p75NTR) is essential for brain lesion formation and functional impairment after experimental traumatic brain injury.
Traumatic brain injury (TBI) initiates an excessive mediator release of e.g. neurotrophins, which promote neuronal survival, differentiation, and modulate synaptic plasticity. Paradoxically, mature forms of neurotrophins promote neuronal survival, whereas unprocessed forms of neurotrophins induce cell death through p75 neurotrophin receptor (p75NTR) signaling. p75NTR is widely expressed during synaptogenesis and is subsequently downregulated in adulthood. Repair mechanisms after acute cerebral insults can reactivate its expression. ⋯ Pharmacological inhibition of the p75NTR signaling reduced lesion volume by 18%. The present study presents first time evidence that genetic mutation of the neurotrophin interaction site of p75NTR strongly limits post-traumatic cell death. In addition, we revealed pharmacological targeting of the intracellular p75NTR cell death domain as a promising approach to limit acute brain damage.