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. · Nov 2010
Neuroglobin protects neurons against oxidative stress in global ischemia.
Neuroglobin (Ngb) is a recently discovered globin that affords protection against hypoxic/ischemic-induced cell injury in brain. Hypoxic/ischemic injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). In previous studies, we found that Ngb has antioxidative properties, and protects PC-12 cells against hypoxia- and β-amyloid-induced cell death. ⋯ After ischemia-reperfusion, CA1 ROS/RNS production and lipid peroxidation were markedly decreased in Ngb transgenic mice compared with wild-type mice. Furthermore, CA1 neuronal injury was also markedly reduced. Thus, Ngb may confer protection against ischemia-reperfusion injury in the brain through its intrinsic antioxidant properties.
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J. Cereb. Blood Flow Metab. · Sep 2010
ReviewHyperglycemia in aneurysmal subarachnoid hemorrhage: a potentially modifiable risk factor for poor outcome.
Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) occurs frequently and is associated with delayed cerebral ischemia (DCI) and poor clinical outcome. In this review, we highlight the mechanisms that cause hyperglycemia after aSAH, and we discuss how hyperglycemia may contribute to poor clinical outcome in these patients. ⋯ In these patients, IIT seems to be difficult to achieve in terms of lowering blood glucose levels substantially without an increased risk of (serious) hypoglycemia. Therefore, before initiating a large-scale randomized trial to investigate the clinical benefit of IIT, phase II studies, possibly with the help of cerebral blood glucose monitoring by microdialysis, will first have to improve this therapy in terms of both safety and adequacy.
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Measuring the global cerebral metabolic rate of oxygen (CMRO(2)) is a valuable tool for assessing brain vitality and function. Measurement of blood oxygen saturation (HbO(2)) and flow in the major cerebral outflow and inflow vessels can provide a global estimate of CMRO(2). We demonstrate a rapid noninvasive method for quantifying CMRO(2) by simultaneously measuring venous oxygen saturation in the superior sagittal sinus with magnetic resonance susceptometry-based oximetry, a technique that exploits the intrinsic susceptibility of deoxygenated hemoglobin, and the average blood inflow rate with phase-contrast magnetic resonance imaging. ⋯ These values are in good agreement with those reported in literature. The technique described is noninvasive, robust, and reproducible for in vivo applications, making it ideal for use in clinical settings for assessing the pathologies associated with dysregulation of cerebral metabolism. In addition, the short acquisition time (approximately 30 seconds) makes the technique suitable for studying the temporal variations in CMRO(2) in response to physiologic challenges.
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J. Cereb. Blood Flow Metab. · Aug 2010
Activation of NR2A receptors induces ischemic tolerance through CREB signaling.
Previous exposure to a nonlethal ischemic insult protects the brain against subsequent harmful ischemia. N-methyl-D-aspartate (NMDA) receptors are a highly studied target of neuroprotection after ischemia. Recently, NMDA receptor subtypes were implicated in neuronal survival and death. ⋯ Elevated brain-derived neurotrophic factor (BDNF) transcriptional activities were observed after sublethal OGD and administration of bicuculline and 4-aminopiridine. NR2A-containing NMDA receptors and CREB signaling have important functions in the induction of ischemic tolerance. This may provide potential novel therapeutic strategies to treat ischemic stroke.
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J. Cereb. Blood Flow Metab. · Jun 2010
ReviewTherapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials?
Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. ⋯ In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.