Journal of neurotrauma
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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
Transplantation of adult rat spinal cord stem/progenitor cells for spinal cord injury.
Stem/progenitor cells derived from the ependymal region of the spinal cord have the ability to self-renew and are multipotential for neurons and glia. These cells may have the ability to regenerate the injured mammalian spinal cord as they do in some lower vertebrates. However, the optimal conditions for transplantation and the fate of transplanted cells are not fully known. ⋯ A significant increase in cell survival was also seen in rats receiving subacute transplants at 9 days after injury. Transplanted cells differentiated primarily into astrocytes (31.2%) and oligodendrocytes (50.3%), and a small number of neurons (1%). No improvement was seen in the Basso, Beattie and Bresnahan (BBB) locomotor rating scale after acute transplantation as compared with injury only, although surviving transplanted cells were identified that had migrated across the injury site from the rostral and caudal injection sites.
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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.