Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral edema is the most frequent serious complication of diabetic ketoacidosis (DKA) in children, occurring in 1% to 5% of DKA episodes. The rates of mortality and permanent neurologic morbidity from this complication are high. The pathophysiologic mechanisms underlying DKA-related cerebral edema are unclear. A number of past and more recent studies have investigated biochemical and therapeutic risk factors for the development of cerebral edema. Recent studies have shown that a higher initial serum urea nitrogen concentration and lower initial partial pressure of carbon dioxide are associated with the development of cerebral edema. This and other information suggests that the pathophysiology of DKA-related cerebral edema may involve cerebral ischemia.
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PMID:Cerebral edema in children with diabetic ketoacidosis. 1276 56

Periventricular leukomalacia (PVL), the major substrate of cerebral palsy in survivors of prematurity, is defined as focal periventricular necrosis and diffuse gliosis in immature cerebral white matter. We propose that nitrosative and/or oxidative stress to premyelinating oligodendrocytes complicating cerebral ischemia in the sick premature infant is a key mechanism of injury interfering with maturation of these cells to myelin-producing oligodendrocytes and subsequent myelination. Using immunocytochemical markers in autopsy brain tissue from 17 PVL cases and 28 non-PVL controls, we found in the PVL cases: 1) selective regionalization of white matter injury, including preferential involvement of the deep compared to intragyral white matter; 2) prominent activation of microglia diffusely throughout the white matter; 3) protein nitration and lipid peroxidation in premyelinating oligodendrocytes in the diffuse component; 4) preferential death of premyelinating oligodendrocytes diffusely; and 5) virtual sparing of the overlying cerebral cortex, as demonstrated by markers of activated astrocytes and microglia. These data establish that PVL is primarily a white matter disease that involves injury to premyelinating oligodendrocytes, potentially through activation of microglia and release of reactive oxygen and nitrogen species. Agents that prevent nitrosative and oxidative stress may play a key role in ameliorating PVL in premature infants in the intensive care nursery.
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PMID:Nitrosative and oxidative injury to premyelinating oligodendrocytes in periventricular leukomalacia. 1276 84

A series of 2 (1H)-quinoxalin-2-one derivatives: 1-alkyl-3-methyl-2 (1H)-quinoxalin-2-one (AMQ, alkyl = H, CH3, C2H5, n-C3H7, n-C5H11, n-C16H33) have been studied by ultraviolet spectrometry. They may be used as highly active fungicides, compounds inhibiting the growth of plants, neuroprotectant for cerebral ischemia, new fluorescent probes, selective antagonists to alpha-amino-3-hydroxy-5-methly-4-isoxazole propionic acid (AMPA) et al. Results show that as the length of the alky1 chain at the nitrogen on the 1-position increases, little changes have been found in the ultraviolet absorption spectra. All spectra have similar peak shape, a strong shoulder peak appears around 327 and 340 nm with a weaker peak around 280 nm. The peak about 340 nm in the UV spectrum is mainly due to the transition of n-->pi* and pi-->pi*, the intense absorption peak about 327 and 280 nm is as the result of the transition of pi-->pi*.
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PMID:[Study on the ultraviolet spectrum in a series of 2 (1H)-quinoxalin-2-one derivatives]. 1293 89

The role of the neural messenger nitric oxide (NO) in cerebral ischaemia has been investigated extensively in the past decade. NO may play either a protective or destructive role in ischaemia and the literature is plagued with contradictory findings. Working with NO presents many unique difficulties and here we review the potential artifacts that may have contributed to discrepancies and cause future problems for the unwary investigator. Recent evidence challenges the idea that NO from neurones builds up to levels (micromolar) sufficient to directly elicit cell death during the post-ischaemic period. Concomitantly, the case is strengthened for a role of NO in delayed death mediated post-ischaemia by the inducible NO synthase. Mechanistically it seems unlikely that NO is released in high enough quantities to inhibit respiration in vivo; the formation of reactive nitrogen species, such as peroxynitrite, represents the more likely pathway to cell death. The protective and restorative properties of NO have become of increasing interest. NO from endothelial cells may, via stimulating cGMP production, protect the ischaemic brain by acutely augmenting blood flow, and by helping to form new blood vessels in the longer term (angiogenesis). Elevated cGMP production may also stop cells dying by inhibiting apoptosis and help repair damage by stimulating neurogenesis. In addition NO may act as a direct antioxidant and participate in the triggering of protective gene expression programmes that underlie cerebral ischaemic preconditioning. Better understanding of the molecular mechanisms by which NO is protective may ultimately identify new potential therapeutic targets.
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PMID:Nitric oxide and its role in ischaemic brain injury. 1503 12

The extracellular signal regulated protein kinases (ERK1/2) are essential for normal development and functional plasticity of the central nervous system. However, a growing number of recent studies in models of cerebral ischemia, brain trauma and neurodegenerative diseases implicate a detrimental role for ERK1/2 signaling during oxidative neuronal injury. Neurons undergoing oxidative stress-related injuries typically display a biphasic or sustained pattern of ERK1/2 activation. A variety of potential targets of reactive oxygen species and reactive nitrogen species could contribute to ERK1/2 activation. These include cell surface receptors, G proteins, upstream kinases, protein phosphatases and proteasome components, each of which could be direct or indirect targets of reactive oxygen or nitrogen species, thereby modulating the duration and magnitude of ERK1/2 activation. Neuronal oxidative stress also appears to influence the subcellular trafficking and/or localization of activated ERK1/2. Differences in compartmentalization of phosphorylated ERK1/2 have been observed in diseased or injured human neurons and in their respective animal and cell culture model systems. We propose that differential accessibility of ERK1/2 to downstream targets, which is dictated by the persistent activation of ERK1/2 within distinct subcellular compartments, underlies the neurotoxic responses that are driven by this kinase.
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PMID:Oxidative neuronal injury. The dark side of ERK1/2. 1515 95

Nicotinamide (vitamin B(3)) reduces the infarct volume following focal cerebral ischemia in rats; however, its mechanism of action has not been reported. After cerebral ischemia and/or reperfusion, reactive oxygen species (ROS) and reactive nitrogen species may be generated by inflammatory cells through several cellular pathways, which can lead to intracellular calcium influx and cell damage. Therefore, we investigated the mechanisms of action of nicotinamide in neuroprotection under conditions of hypoxia/reoxygenation. Results showed that nicotinamide significantly protected rat primary cortical cells from hypoxia by reducing lactate dehydrogenase release with 1 h of oxygen-glucose deprivation (OGD) stress. ROS production and calcium influx in neuronal cells during OGD were dose-dependently diminished by up to 10 mM nicotinamide (p < 0.01). This effect was further examined with OGD/reoxygenation (H/R). Cells were stained with the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI) or antibodies against anti-microtubule-associated protein-2 and cleaved caspase-3. Apoptotic cells were studied using Western blotting of cytochrome c and cleaved caspase-3. Results showed that vitamin B(3) reduced cell injury, caspase-3 cleavage and nuclear condensation (DAPI staining) in neuronal cells under H/R. In addition, nicotinamide diminished c-fos and zif268 immediate-early gene expressions following OGD. Taken together, these results indicate that the neuroprotective effect of nicotinamide might occur through these mechanisms in this in vitro ischemia/reperfusion model.
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PMID:Protective effect of nicotinamide on neuronal cells under oxygen and glucose deprivation and hypoxia/reoxygenation. 1515 82

N-Methyl-D-aspartate receptor antagonism contributes to the anesthetic action of nitrous oxide (N(2)O). We examined the effects of the N-methyl-D-aspartate antagonists N(2)O and dizocilpine on outcome from filament occlusion of the middle cerebral artery (MCAO). Rats breathed 70% nitrogen/30% oxygen or 70% N(2)O/30% oxygen during MCAO. A third group breathed 70% nitrogen/30% oxygen and was given dizocilpine (0.25 mg/kg IV). After 75 min of MCAO, the rats recovered for 3 or 14 days. Pericranial temperature was maintained at 37.5 degrees C +/- 0.2 degrees C during ischemia and for 20 h postischemia. N(2)O did not alter neurologic scores at 3 days (N(2)O, 21 +/- 6; nitrogen, 22 +/- 8; P = 0.95; 0 = normal; 48 = maximal deficit; mean +/- sd; n = 15) or 14 days (N(2)O, 13 +/- 6; nitrogen, 12 +/- 6; P = 0.93; n = 15-16) postischemia. N(2)O had no effect on infarct size at 3 days (N(2)O, 162 +/- 45 mm(3); nitrogen, 162 +/- 61 mm(3); P > 0.99) or 14 days (N(2)O, 147 +/- 56 mm(3); nitrogen, 151 +/- 62 mm(3); P = 0.99) postischemia. Dizocilpine treatment caused smaller infarcts (3 days: 66 +/- 49 mm(3), P < 0.0001 versus nitrogen; 14 days: 84 +/- 50 mm(3), P < 0.006 versus nitrogen) and reduced the neurologic deficit (3 days: 10 +/- 10, P = 0.002 versus nitrogen; 14 days: 6 +/- 7, P = 0.006 versus nitrogen). N(2)O (70%) had no effect on either behavioral or histologic outcome from transient focal cerebral ischemia when compared with results in rats breathing 70% nitrogen. These results indicate that normobaric N(2)O does not alter the response of rat brain to a focal ischemic insult.
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PMID:Intraischemic nitrous oxide alters neither neurologic nor histologic outcome: a comparison with dizocilpine. 1603 6

Cerebral ischemia induces a complex series of molecular pathways involving signaling mechanisms, gene transcription, and protein formation. The proteases and free radicals involved are important, both individually and in concert, at each of the steps in the injury cascade. Matrix metalloproteinases (MMPs) and serine proteases are essential in the breakdown of the extracellular matrix around cerebral blood vessels and neurons, and their action leads to opening of the blood-brain barrier, brain edema, hemorrhage, and cell death. Reactive oxygen and nitrogen species affect the signaling pathways that induce the enzymes, the stability of the mRNA, and their activation processes. Mice that either lack MMP genes or overexpress free radical-removing genes exhibit diminished cerebral damage after stroke. Drugs that block MMP activity, or are free radical scavengers, significantly reduce ischemic damage. Understanding the relationship between proteases and free radicals in cerebral ischemia is critical for the design of therapeutic agents aimed at controlling cell death in ischemic tissues.
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PMID:Matrix metalloproteinases and free radicals in cerebral ischemia. 1592 79

It is now understood that the mechanisms leading to neuronal cell death after cerebral ischemia are highly complex. A well established fact in this field is that neurons continue to die over days and months after ischemia, and that reperfusion following cerebral ischemia contributes substantially to ischemic injury. It is now well accepted that central to ischemic/reperfusion-induced injury is what occurs to mitochondria hours to days following the ischemic insult. For many years, it has been established that reactive oxygen species (ROS) and reactive nitrogen species (RNS) promote lipid, protein, and DNA oxidation that affects normal cell physiology and eventually leads to neuronal demise. In addition to oxidation of neuronal molecules by ROS and RNS, a novel pathway for molecular modifications has risen from the concept that ROS can activate specific signal transduction pathways that, depending on the insult degree, can lead to either normal plasticity or pathology. Two examples of these pathways could explain why lethal ischemic insults lead to the translocation of protein kinase Cdelta (deltaPKC), which plays a role in apoptosis after cerebral ischemia, or why sublethal ischemic insults, such as in ischemic preconditioning, lead to the translocation of epsilonPKC, which plays a pivotal role in neuroprotection. A better understanding of the mechanisms by which ROS and/or RNS modulate key protein kinases that are involved in signaling pathways that lead to cell death and survival after cerebral ischemia will help devise novel therapeutic strategies.
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PMID:Role of reactive oxygen species and protein kinase C in ischemic tolerance in the brain. 1611 18

Being the second most common cause of death in the industrial countries and one of the major causes of death and disability, stroke has a great effect on public health and is the neurological disease which accounts for the largest number of hospitalizations. In order to develop new treatments, biochemical mechanisms involved in brain damage have been investigated. Among them, oxidant species generated during stroke have been implicated as critical mediators of neuronal injury in this condition, although neuroprotective roles have also been demonstrated. This review is focused on the role of the mitochondrial respiratory chain as both source and target of reactive oxygen and nitrogen species such as nitric oxide, superoxide and peroxynitrite produced in cerebral ischemia. The neuroprotective role of antioxidants or other molecules acting on the mitochondrial respiratory chain and ATP synthesis in the setting of cerebral ischemia is discussed.
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PMID:Mitochondrial respiratory chain and free radical generation in stroke. 1625 38


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