Journal of neurotrauma
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Journal of neurotrauma · Feb 2014
Early Platelet Dysfunction in a Rodent Model of Blunt Traumatic Brain Injury Reflects the Acute Traumatic Coagulopathy Found in Humans.
Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. ⋯ Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.
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Journal of neurotrauma · Feb 2014
Erythropoietin Improved Cognitive Function and Decreased Hippocampal Caspase Activity in Rat Pups after Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading cause of acquired neurologic disability in children. Erythropoietin (EPO), an anti-apoptotic cytokine, improved cognitive outcome in adult rats after TBI. To our knowledge, EPO has not been studied in a developmental TBI model. ⋯ EPO normalized recognition memory after CCI. EPO blunted the increased hippocampal caspase activity induced by CCI at PID1, but not at PID2. EPO increased neuron fraction in CA3 at PID2. Brain levels of exogenous EPO appeared low relative to endogenous. Timing of EPO administration was associated with temporal changes in hippocampal mRNA levels of EPO and pro-apoptotic factors. Conclusion/Speculation: EPO improved recognition memory, increased regional hippocampal neuron fraction, and decreased caspase activity in P17 rats after CCI. We speculate that EPO improved cognitive outcome in rat pups after CCI as a result of improved neuronal survival via inhibition of caspase-dependent apoptosis early after injury.
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Journal of neurotrauma · Feb 2014
Evidence for impaired plasticity after traumatic brain injury in the developing brain.
The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating. ⋯ Indeed, corpus callosum abnormalities in TBI rats were detected with diffusion tensor imaging (9.3% decrease in fractional anisotropy) and histopathological analysis (14% myelination volume decreases). Whole-cell patch clamp recordings further revealed that TBI results in significant decreases in spontaneous firing rate (57% decrease) and the potential to induce long-term potentiation in neurons located in layer V of the noninjured S1 by stimulation of the corpus callosum (82% decrease). The results suggest that post-TBI plasticity can translate into inappropriate neuronal connections and dramatic changes in the function of neuronal networks.
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Journal of neurotrauma · Feb 2014
The Effect of Hypothermia on the Expression of TIMP-3 After Traumatic Brain Injury in Rats.
Here we investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. We began with 210 adult male Sprague-Dawley rats and randomly assigned them to three groups: TBI with hypothermia treatment (32°C), TBI with normothermia (37°C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. ⋯ In contrast, post-traumatic hypothermia significantly attenuated this increase. According to the RT-PCR and Western blot analyses, the maximum mRNA levels of TIMP-3 were reduced to 60.60 ± 2.30%, 55.83 ± 1.80%, 66.03 ± 2.10%, and 64.51 ± 1.50%, respectively, of the corresponding values in the normothermic group in the injured and uninjured hemispheres (cortex and hippocampus) of the hypothermia group (p < 0.01), while the respective maximum protein levels of TIMP-3 were reduced to 57.50 ± 1.50, 52.67 ± 2.20, 60.31 ± 2.50 and 54.76 ± 1.40 (p < 0.01). Our data suggest that moderate fluid percussion brain injury significantly upregulates TIMP-3 expression, and that this increase may be suppressed by hypothermia treatment.
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Journal of neurotrauma · Feb 2014
Amantadine Improves Cognitive Outcome and Increases Neuronal Survival after Fluid Percussion TBI in Rats.
This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. ⋯ Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI.