Journal of neurotrauma
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Journal of neurotrauma · Sep 2004
Comparative StudyThe protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury.
Pre- and post-injury Cyclosporin A (CsA) administration has shown neuroprotective properties by ameliorating mitochondrial damage. The aim of this study was to assess the effect of CsA upon N-acetylaspartate (NAA) reduction and ATP loss, two sensitive markers of mitochondrial dysfunction and bioenergetic impairment. Adult male Sprague-Dawley rats were exposed to impact acceleration traumatic brain injury (2 m/450 g) and randomized into the following experimental groups: intrathecal CsA/vehicle treated (n = 12), intravenous CsA/vehicle treated (n = 18) and sham (n = 12). ⋯ In conclusion, CsA is capable of restoring ATP and blunting NAA reduction. Intravenous infusion of 35 mg/kg appears to be the optimal therapeutic strategy in this model. These findings contribute to the notion that CsA achieves neuroprotection, preserving mitochondrial function, and provides a rationale for the assessment of CsA in the clinical setting where MR spectroscopy can monitor NAA and ATP in brain-injured patients.
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Journal of neurotrauma · Sep 2004
Comparative StudyCerebral pressure autoregulation is intact and is not influenced by hypothermia after traumatic brain injury in rats.
In head-injured patients and experimental traumatic brain injury (TBI), important cerebrovascular abnormalities include decreases in cerebral blood flow (CBF) and impairment of cerebral pressure autoregulation. We evaluated CBF and pressure autoregulation after fluid percussion injury (FPI) and hypothermia in rats with the hypothesis that hypothermia would ameliorate changes in posttraumatic CBF. Male Sprague-Dawley rats, intubated and mechanically ventilated, were prepared for parasagittal FPI (1.8 atm) and laser Doppler CBF flow (LDF) measurement. ⋯ Thus, in these experiments, absolute CBF decreased with hypothermia and FPI, while neither hypothermia nor FPI significantly altered autoregulation. In the second study, autoregulatory function was not different before TBI when comparing random and sequential blood pressure changes, but, when comparing the groups after TBI at the 60 mm Hg blood pressure level, CBF was significantly lower in the sequential group than in the random order group. This suggests that the mechanism of creating hypotension, whether random or sequential, significantly affects the measurement of CBF and autoregulation after TBI in rats.
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Journal of neurotrauma · Aug 2004
Effect of age at time of spinal cord injury on behavioral outcomes in rat.
Spinal cord injury (SCI) often leads to chronic central pain (CCP) syndromes such as allodynia and hyperalgesia. Although several experimental animal models for CCP studies exist, little is known about the effect of age on the development of CCP following SCI. In this study, we evaluated behavioral responses to mechanical and thermal stimuli following SCI using three different age groups of adult Sprague-Dawley rats: young (40 days), adult (60 days), and middle-age (12 months). ⋯ In both forelimbs and hindlimbs, the young group displayed a significant increase in PWF and a significant decrease in PWL compared to presurgical and sham values or values from the adult and middle-age groups. These results indicate that younger rats developed more robust neuropathic behaviors than middle-age rats, indicating that age selection is an important factor in animal models of CCP syndromes following SCI. Additionally, our data suggest that age at the time of injury may be one risk factor in predicting the development of CCP after SCI in people.
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Journal of neurotrauma · Aug 2004
Increased expression of vasopressin v1a receptors after traumatic brain injury.
Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats. ⋯ This increase in the V1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1-2 h following the impact, there was also a striking increase in the number of the V1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.
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Journal of neurotrauma · Aug 2004
Erythropoietin attenuates post-traumatic injury in organotypic hippocampal slices.
Recent experimental evidence indicates that erythropoietin (Epo), in addition to its hormonal role in regulating red cell production, operates as a neuroprotective agent. So far, the neuroprotective effect of human recombinant Epo (rhEpo) has been mainly demonstrated in models of cerebral ischemia/hypoxia and in selected in vivo studies of traumatic neuronal injury. To further investigate the potential role of this multifunctional trophic factor in post-traumatic cell death, we examined the protective effects of rhEpo in a newly developed model of mechanical trauma in organotypic hippocampal slices. ⋯ At 48 h after trauma, the protective effect of rhEpo was greater (by about 47%) and significantly more pronounced than that of MK-801 (28%). Our results suggest that the neuroprotective activity of rhEpo is particularly effective against delayed, secondary post-traumatic damage. This well tolerated agent could provide a therapeutic benefit in pathologies involving post-traumatic neurodegeneration.