Journal of neurotrauma
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Journal of neurotrauma · Sep 2004
Comparative StudyTransplantation of Schwann cells and olfactory ensheathing glia after spinal cord injury: does pretreatment with methylprednisolone and interleukin-10 enhance recovery?
Methylprednisolone (MP) and interleukin-10 (IL-10) are tissue protective acutely after spinal cord injury (SCI); their combination offers additive protection (Takami et al., 2002a). Our study examined if acute administration of MP (30 mg/kg i.v. at 5 min, and 2 and 4 h after injury) and IL-10 (30 mg/kg i.p. at 30 min after injury) increases the efficacy of Schwann cell (SC) or SC plus olfactory ensheathing glia (SC/OEG) grafts transplanted into rat thoracic cord 1 week after contusive injury. Efficacy was determined by histology, anterograde and retrograde tracing, immunohistochemistry for gliosis and specific nerve fibers, and several behavioral tests. ⋯ Only the combination of MP/IL-10 with SC/OEG transplants significantly improved gross locomotor performance (BBB scores) over injury-only controls. MP/IL-10 given prior to SC-only transplants, however, worsened behavioral outcome. Because beneficial effects of MP/IL-10 were not always additive when combined with cell transplantation, we need to understand (1) how tissue protective agents may transform the milieu of the injured spinal cord to the benefit or detriment of later transplanted cells and (2) whether neuroprotectants need to be re-administered at the time of cell grafting or less invasive transplantation techniques employed to reduce damage to tissue spared by an earlier protection strategy.
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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 · Sep 2004
Multicenter Study Comparative StudyAssessment of the macrophage marker quinolinic acid in cerebrospinal fluid after pediatric traumatic brain injury: insight into the timing and severity of injury in child abuse.
This study measured quinolinic acid (QUIN), a macrophage-microglia derived neurotoxin, in the cerebrospinal fluid (CSF) of children after non-inflicted and inflicted traumatic brain injury (nTBI, iTBI), and correlated QUIN concentrations with age, mechanism of injury (nTBi vs. iTBI), Glasgow Coma Scale (GCS) score and 6-month Glasgow Outcome Score. One hundred fifty-two CSF samples were collected from 51 children with severe TBI (GCS < or = 8). CSF was collected at the time an intraventricular catheter was placed and daily thereafter. ⋯ Despite the lack of a history of trauma in 82% of children with iTBI, 100% had a peak QUIN concentration of >100 nM. There was a significant increase in the CSF concentrations of QUIN following severe nTBI and iTBI in children. Higher initial and peak QUIN concentrations after iTBI may be due to severity of injury, young age, and/or delay in seeking medical care, which allows for increased secondary injury.
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Journal of neurotrauma · Sep 2004
Comparative StudyComparison of tetrahydrobiopterin and L-arginine on cerebral blood flow after controlled cortical impact injury in rats.
The purpose of this study was to compare the effects of L-arginine and tetrahydrobiopterin administration on post-traumatic cerebral blood flow (CBF) and tissue levels of NO in injured brain tissue. Rats were anesthetized with isoflurane. Mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations were measured prior to, and for 2 h after a controlled cortical impact injury. ⋯ NO concentration also decreased by approximately 20 pmol/ml from baseline values. L-arginine and tetrahydrobiopterin administration both resulted in a significant preservation of tissue NO concentrations and an improvement in LDF, compared to control animals given saline. These studies demonstrate that tetrahydrobiopterin administration has a beneficial effect on cerebral blood flow that is similar to L-arginine administration, and may suggest that depletion of tetrahydrobiopterin plays a role in the post-traumatic hypoperfusion of the brain.