Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Oct 2003
Cerebrovascular vasodilation to extraluminal acidosis occurs via combined activation of ATP-sensitive and Ca2+-activated potassium channels.
Albeit controversial, it has been suggested by several authors that nitric oxide (NO) serves as a permissive factor in the cerebral blood flow response to systemic hypercapnia. Potassium channels are important regulators of cerebrovascular tone and may be modulated by a basal perivascular NO level. To elucidate the functional targets of the proposed NO modulation during hypercapnia-induced vasodilation, the authors performed experiments in isolated, cannulated, and pressurized rat middle cerebral arteries (MCA). ⋯ During NO synthase inhibition, dilation to the KATP channel opener pinacidil or the KCa channel opener NS1619 was attenuated or abolished, respectively. The authors suggest that a basal perivascular NO level is necessary for physiologic KATP and KCa channel function in rat MCA. Future studies have to elucidate whether this NO dependent effect on KATP and KCa channel function is a principle mechanism of NO induced modulation of cerebrovascular reactivity and whether the variability of findings in the literature concerning a modulatory role of NO can be explained by different levels of vascular NO/cGMP concentrations within the cerebrovascular tree.
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J. Cereb. Blood Flow Metab. · Sep 2003
Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat.
The inflammatory response that exacerbates cerebral injury after ischemia is an attractive therapeutic target: it progresses over days and strongly contributes to worsening of the neurologic outcome. The authors show that, after transient ischemic injury to the rat brain, systemic application of interferon-beta (IFN-beta), a cytokine with antiinflammatory properties, attenuated the development of brain infarction. Serial magnetic resonance imaging (MRI) showed that IFN-beta treatment reduced lesion volume on diffusion-weighted MRI by 70% (P < 0.01) at 1 day after stroke. ⋯ Gelatinase zymography showed that this effect was associated with a decrease in matrix metalloproteinase-9 expression. In conclusion, treatment with the antiinflammatory cytokine IFN-beta affords significant neuroprotection against ischemia/reperfusion injury, and within a relatively long treatment window. Because IFN-beta has been approved for clinical use, it may be rapidly tested in a clinical trial for its efficacy against human stroke.
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J. Cereb. Blood Flow Metab. · Aug 2003
L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study.
There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 +/- 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. ⋯ In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.
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J. Cereb. Blood Flow Metab. · Aug 2003
Evidence for a lactate pool in the rat brain that is not used as an energy supply under normoglycemic conditions.
Lactate derived from glucose can serve as an energy source in the brain. However, it is not certain how much lactate, directly taken from the blood circulation, may replace glucose as an energy source. This study aimed to estimate the uptake, release, and utilization of lactate entering the brain from the blood circulation. ⋯ Immediately after the infusion there was a net efflux of lactate from the brain. The results suggest that the majority of lactate moving into the brain is not used as an energy substrate, and that lactate does not replace glucose as an energy source. Instead, the authors propose the concept of a lactate pool in the brain that can be filled and emptied in accordance with the blood lactate concentration, but which is not used as an energy supply for cerebral metabolism.
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J. Cereb. Blood Flow Metab. · Jul 2003
Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study.
Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. ⋯ Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.