Journal of neurotrauma
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Journal of neurotrauma · Oct 2015
Increased network excitability due to altered synaptic inputs to neocortical layer V intact and axotomized pyramidal neurons after mild traumatic brain injury.
Mild traumatic brain injury (mTBI) can produce long lasting cognitive dysfunction. There is typically no cell death and only diffuse structural injury after mTBI. Thus, functional changes in intact neurons may contribute to symptoms. ⋯ The amplitude of this evoked negativity was significantly larger than controls over a series of stimulus intensities at both the 1 d and 2 d survival times. Interictal-like spikes never occurred in the field potential recordings from controls but were observed in 20-80% of stimulus presentations in injured cortex. Together, these results suggest an overall increase in network excitability and the production of particularly powerful (intact) neurons that have both increased intrinsic and synaptic excitability.
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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.
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Journal of neurotrauma · Oct 2015
Head trauma with or without mild brain injury increases the risk of future traumatic death: A controlled prospective 15-year follow-up study.
Patients who have recovered from traumatic brain injury (TBI) show an increased risk of premature death. To investigate long-term mortality rates in a population admitted to the hospital for head injury (HI), we conducted a population-based prospective case-control, record-linkage study, All subjects who were living in Northern Ostrobothnia, and who were admitted to Oulu University Hospital in 1999 because of HI (n=737), and 2196 controls matched by age, gender, and residence randomly drawn from the population of Northern Ostrobothnia were included. Death rate and causes of death in HI subjects during 15 years of follow-up was compared with the general population controls. ⋯ The main founding was that even HI without TBI carries an increased risk of future traumatic death. The reason for this remains unknown and further studies are needed. To prevent such premature deaths, post-traumatic therapy should include an interview focusing on lifestyle factors.
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Journal of neurotrauma · Oct 2015
Mathematical difficulties and white matter abnormalities in subacute pediatric mild traumatic brain injury.
Mathematical difficulties have been documented following pediatric mild traumatic brain injury (mTBI), yet a precise characterization of these impairments and their neural correlates is currently unavailable. We aimed to characterize these impairments by comparing behavioral and neuroimaging (i.e., diffusion tensor imaging [DTI]) outcomes from children with subacute mTBI to typically-developing controls. Twenty subacute pediatric mTBI patients and 20 well-matched controls underwent cognitive assessment and DTI examination. ⋯ Behavioral results revealed that children with mTBI performed significantly more poorly on rapid apprehension of small numbers of objects (or "subitizing"), processing of non-symbolic numerosities, and procedural problem solving. These group differences were explained by differences in visuospatial working memory, which suggests that the observed mathematical difficulties may be a consequence of impairments in visuospatial abilities. DTI analysis revealed subtle group differences in the CC genu and splenium (i.e., higher fractional anisotropy and lower mean and radial diffusivity in children with mTBI) but the observed white matter abnormalities of the CC were not significantly associated with the observed mathematical difficulties in the mTBI patients.
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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.