Experimental neurology
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Experimental neurology · Feb 2000
Continuous infusion of cyclosporin A postinjury significantly ameliorates cortical damage following traumatic brain injury.
Traumatic brain injury (TBI) results in the rapid necrosis of cortical tissue at the site of injury. In the ensuing hours and days, secondary injury exacerbates the original damage resulting in significant neurological dysfunction. Recent reports from our lab demonstrate that a bolus injection of the immunosuppressant cyclosporin A (CsA) is neuroprotective following TBI. ⋯ All animals receiving CsA demonstrated a significant reduction in lesion volume, with the highest dose offering the most neuroprotection (74% reduction in lesion volume). These results extend our previous findings and demonstrate that chronic infusion of CsA is neuroprotective following TBI. These findings also suggest that the mechanisms responsible for tissue necrosis following TBI are amenable to manipulation.
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Experimental neurology · Feb 2000
Growth factors in combination, but not individually, rescue rd mouse photoreceptors in organ culture.
The rd mouse retina is an animal model for human retinal dystrophy in which the rod photoreceptors undergo apoptosis during the first 4 weeks in vivo or in organ culture. We have examined the effect of different families of trophic factors on the survival of rd mouse photoreceptors in organ culture. Retinas were harvested from rd mice at postnatal day 2 and grown in organ culture for 27 days in vitro (DIV) in DMEM with 10% fetal calf serum. ⋯ A significant increase in photoreceptor survival was seen with forskolin added to CNTF, but not to BDNF, FGF2, or GDNF. These results demonstrate that trophic factors promote photoreceptor survival through a synergistic interaction. Increased understanding of receptor interactions and signaling pathways may lead to a potential therapeutic role for combinatorial trophic factors in treatment of photoreceptor dystrophies.
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Experimental neurology · Jan 2000
Effects of spinal cord X-irradiation on the recovery of paraplegic rats.
Axonal regrowth is limited in the adult CNS, especially in the spinal cord, one of the major sites of traumatic lesions. Pathophysiological changes occurring after spinal cord injury include complex acute, subacute, and late processes. In this study, we assessed whether X-irradiation interferes with the acute/subacute phases, thereby improving the functional recovery of paraplegic animals. ⋯ There was a 23% less lesion-induced syringomyelia in the 2-Gy group than in the other groups (LNI and 5-20 Gy). Thus, low doses of X-rays may interfere with the formation of syringomyelia and glial scar, thereby facilitating the recovery of paraplegic animals. These findings suggest that low-dose irradiation of the lesion site, in association with other therapies, is a potentially promising treatment for improving recovery after spinal cord injury.
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Experimental neurology · Jan 2000
Light and confocal microscopic studies of evolutionary changes in neurofilament proteins following cortical impact injury in the rat.
Previous studies have shown that traumatic brain injury (TBI) produces progressive degradation of cytoskeletal proteins including neurofilaments (e.g., neurofilament 68 [NF68] and neurofilament 200 [NF200]) within the first 24 h after injury. Thus, we employed immunofluorescence (light and confocal microscopy) to study the histopathological correlates of progressive neurofilament protein loss observed at 15 min, 3 h, and 24 h following unilateral cortical injury in rats. TBI produced significant alterations in NF68 and NF200 immunolabeling in dendrites and cell bodies at contusion sites ipsilateral to injury, as well as in the noncontused contralateral cortex. ⋯ Moreover, changes in dendritic cytoskeletal proteins are progressive and not fully expressed within the first 15 min following impact injury. These progressive dendritic disruptions are characterized by disturbances in the morphology of neurofilament proteins, resulting in fragmentation and focal loss of NF68 immunofluorescence within apical dendrites. In contrast, alterations in axonal cytoskeletal proteins are more restricted and delayed with no pronounced changes until 24 h after injury.
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Experimental neurology · Jan 2000
Neuronal subclass-selective loss of pyruvate dehydrogenase immunoreactivity following canine cardiac arrest and resuscitation.
Chronic impairment of aerobic energy metabolism accompanies global cerebral ischemia and reperfusion and likely contributes to delayed neuronal cell death. Reperfusion-dependent inhibition of pyruvate dehydrogenase complex (PDHC) enzyme activity has been described and proposed to be at least partially responsible for this metabolic abnormality. This study tested the hypothesis that global cerebral ischemia and reperfusion results in the loss of pyruvate dehydrogenase immunoreactivity and that such loss is associated with selective neuronal vulnerability to transient ischemia. ⋯ A significant decrease in immunoreactivity was observed in frontal cortex homogenates from both 2 and 24 h reperfused animals compared to samples from nonischemic control animals. These results were supported by confocal microscopic immunohistochemical determinations of pyruvate dehydrogenase immunoreactivity in the neuronal cell bodies located within different layers of the frontal cortex. Loss of immunoreactivity was greatest for pyramidal neurons located in layer V compared to neurons in layers IIIc/IV, which correlates with a greater vulnerability of layer V neurons to delayed death caused by transient global cerebral ischemia.