Journal of neurotrauma
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Journal of neurotrauma · May 2007
Proteomic identification of oxidized mitochondrial proteins following experimental traumatic brain injury.
Experimental traumatic brain injury (TBI) results in a significant loss of cortical tissue at the site of injury, and in the ensuing hours and days a secondary injury exacerbates this primary injury, resulting in significant neurological dysfunction. The mechanism of the secondary injury is not well understood, but evidence implicates a critical role for mitochondria in this cascade. This mitochondrial dysfunction is believed to involve excitotoxicity, disruption of Ca(2+) homeostasis, production of reactive oxygen species (ROS), ATP depletion, oxidative damage of mitochondrial proteins, and an overall breakdown of mitochondrial bioenergetics. ⋯ In addition, we have also shown that, following TBI, there is a reduction in the activities of pyruvate dehydrogenase (PDH), complex I, and complex IV. These findings demonstrate that, following TBI, several proteins involved in mitochondrial bioenergetics are highly oxidatively modified, which may possibly underlie the massive breakdown of mitochondrial energetics and eventual cell death known to occur in this model. The identification of these proteins provides new insights into the mechanisms that take place following TBI and may provide avenues for possible therapeutic interventions after TBI.
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Journal of neurotrauma · May 2007
Apolipoprotein E4 allele presence and functional outcome after severe traumatic brain injury.
Presence of the apolipoprotein E (APOE) 4 allele has been associated with increased incidence and faster progression of neurodegenerative diseases, poorer recovery from neurologic insult, and decreased cognitive function in the well-elderly. The specific association between APOE genotype and recovery from severe traumatic brain injury (TBI) is conflicting with many groups finding the APOE 4 allele to be associated with poorer outcome while others have found no association. The purpose of this study was to investigate the association between APOE 4 allele presence and recovery during the two years after injury from severe TBI in light of other potential covariates, such as age, race, gender, hypotension or hypoxia before hospital admission and severity of injury. ⋯ We did not however find significant differences in GOS at individual time points when controlling for other covariates. Our findings suggest that APOE 4 allele presence influences recovery rate from severe TBI independent of other covariates. The findings of this study are unique in that they address not only the relationship between APOE 4 allele presence and outcome from severe TBI, but also describe differences in trajectory of recovery by APOE 4 allele presence.
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Journal of neurotrauma · May 2007
Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.
Following experimental traumatic brain injury (TBI), a rapid and significant necrosis occurs at the site of injury which coincides with significant mitochondrial dysfunction. The present study is driven by the hypothesis that TBI-induced glutamate release increases mitochondrial Ca(2+)cycling/overload, ultimately leading to mitochondrial dysfunction. Based on this premise, mitochondrial uncoupling during the acute phases of TBI-induced excitotoxicity should reduce mitochondrial Ca(2+) uptake (cycling) and reactive oxygen species (ROS) production since both are mitochondrial membrane potential dependent. ⋯ These results demonstrate that post-injury treatment with mitochondrial uncouplers significantly (p < 0.01) increases cortical tissue sparing ( approximately 12%) and significantly (p< 0.01) improves behavioral outcome following TBI. The mechanism of neuroprotection most likely involves the maintenance of mitochondrial homeostasis by reducing mitochondrial Ca(2+) loading and subsequent mitochondrial dysfunction. These results further implicate mitochondrial dysfunction as an early event in the pathophysiology of TBI and that targeting acute mitochondrial events can result in long-term neuroprotection and improve behavioral outcome following brain injury.
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Journal of neurotrauma · May 2007
Quantitative characterization of regenerating axons after end-to-side and end-to-end coaptation in a rat brachial plexus model: a retrograde tracer study.
The efficacy of end-to-side repair as a method of nerve reconstruction has been questioned, and most studies that characterize the mode of re-innervation are marred by inappropriate experimental design and lack quantitative analysis. This makes characterization of re-innervating neurons confusing and consequently controversy remains as to the extent and source of reinnervating axons. In an experimental brachial plexus rat model, we transected the musculocutaneous nerve, labeled its neuron pool with Fast-Blue and joined the distal stump to the side of the intact ulnar nerve, or to the proximal stump of the divided ulnar nerve, to characterize neurons that reinnervate the recipient nerve. ⋯ In the end-to-side group, 16.4% of the motor and 7% of the sensory donor ulnar nerve neurons re-innervated the musculocutaneous nerve exclusively, and a further 10% motor and 11.6% sensory innervated the musculocutaneous nerve by collateral sprouting of their axons. This compared to re-innervation by 62.6% of motor and 70.4% of ulnar nerve sensory neurons in the positive control that underwent end-to-end repair. Our results confirm the concept of collateral sprouting and support the use of end-to-side repair.
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In peripheral nerve injury, end-to-side neurorrhaphy has been reported as an alternative in cases that the proximal nerve stump is not accessible. Several hypotheses have been proposed to explain peripheral nerve regeneration after end-to-side neurorrhaphy. Recent evidence suggests that nerve regeneration occurs by collateral sprouting. ⋯ The goal of this technique is to provide satisfactory functional recovery for the recipient nerve, without any deterioration of the donor nerve function. End-to-side technique has been investigated in detail in both experimental and clinical studies. Only a limited number of reported cases in clinical practice, until today, can reveal that end-to-side technique may become a viable means of repairing peripheral nerves in certain clinical situations.