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

Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, alterations in calcium homeostasis lead to persistent, pathologic activation of calpain in a number of neurodegenerative diseases. Pathologic activation of calpain results in the cleavage of a number of neuronal substrates that negatively affect neuronal structure and function, leading to inhibition of essential neuronal survival mechanisms. In this review, we examine the mechanistic underpinnings of calcium dysregulation resulting in calpain activation in the acute neurodegenerative diseases such as cerebral ischemia and in the chronic neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, prion-related encephalopathy, and amylotrophic lateral sclerosis. The premise of this paper is that analysis of the signaling and transcriptional consequences of calpain-mediated cleavage of its various substrates for any neurodegenerative disease can be extrapolated to all of the neurodegenerative diseases vulnerable to calcium dysregulation.
 ...
PMID:Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. 1868 46

Previous investigations have demonstrated that electroacupunctural stimulation can ameliorate primary and secondary symptoms such as peripheral neuropathy and diabetic encephalopathy in diabetic rats. In this study, we investigated whether electroacupuncture could improve learning and memory which was typically impaired in diabetic rats with cerebral ischemia. Furthermore, we investigated the mechanisms underlying its effects using passive avoidance test, active avoidance test, Morris water maze and electrophysiology. Electroacupuncture increased the step-down latency in passive avoidance test and accurate rate in active avoidance test, decreased the escape latency in Morris water maze. After electroacupuncture treatment, the long-term potentiation (LTP) impaired by both diabetes and cerebral ischemia was restored significantly. These results suggest that electroacupuncture can ameliorate learning and memory capacity impaired by hyperglycemia and ischemia. LTP plays a very important role in this beneficial effect.
 ...
PMID:Electroacupuncture restores learning and memory impairment induced by both diabetes mellitus and cerebral ischemia in rats. 1869 47

We studied the effect of antioxidant therapy on the state of glutathione system in erythrocytes in patients with stage 1, 2, and 3 circulatory encephalopathy treated with antioxidant cytoflavin against the background of basic therapy (kavinton and pyracetam). It was demonstrated that the response of the erythrocyte glutathione system to antioxidant therapy was quantitatively and qualitatively different at different stages of cerebrovascular failure, which was related to changes in the glutathione system during the development of chronic cerebral ischemia. Endogenous reserve of the antioxidant defense system should be taken into account when prescribing antioxidant therapy; the glutathione system can be a marker of this reserve.
 ...
PMID:Effect of antioxidant therapy on glutathione system of erythrocytes in chronic brain ischemia. 1952 22

The immature brain is prone to hypoxic-ischemic encephalopathy and stroke. The incidence of arterial stroke in newborns is similar to that in the elderly. However, the pathogenesis of ischemic brain injury is profoundly affected by age at the time of the insult. Necrosis is a dominant type of neuronal cell death in adult brain, whereas widespread neuronal apoptosis is unique for the early postnatal synaptogenesis period. The inflammatory response, in conjunction with excitotoxic and oxidative responses, is the major contributor to ischemic injury in both the immature and adult brain, but there are several areas where these responses diverge. We discuss the contribution of various inflammatory mechanisms to injury and repair after cerebral ischemia in the context of CNS immaturity. In particular, we discuss the role of lower expression of selectins, a more limited leukocyte transmigration, undeveloped complement pathways, a more rapid microglial activation, differences in cytokine and chemokine interplay, and a different threshold to oxidative stress in the immature brain. We also discuss differences in activation of intracellular pathways, especially nuclear factor kappaB and mitogen-activated protein kinases. Finally, we discuss emerging data on both the supportive and adverse roles of inflammation in plasticity and repair after stroke.
 ...
PMID:Does inflammation after stroke affect the developing brain differently than adult brain? 1967 67

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. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. 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.
 ...
PMID:Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? 2035 45

Intravenous recombinant tissue plasminogen activator remains the only US FDA-approved treatment for acute ischemic stroke. However, the very limited time window for its administration restricts its usefulness. Furthermore, it is becoming increasingly clear that, given the numerous pathways via which cerebral ischemia causes cell death, the capacity to inhibit multiple mechanisms simultaneously may provide additive or synergistic beneficial clinical effects for stroke patients. Although no clinical trials have yet investigated the efficacy of therapeutic hypothermia in focal cerebral ischemia, its pleiotropic neuroprotective actions, positive results in preclinical studies, as well as proven enhancement of neurologic outcomes in survivors of cardiac arrest and newborns with hypoxic-ischemic encephalopathy, make this neuroprotective strategy highly promising. This review presents an overview of the potential role of hypothermia in the treatment of acute ischemic stroke and discusses ischemic cell death pathophysiology, neuroprotective mechanisms of hypothermia, methodologies employed for the induction of hypothermia, results from animal models of cerebral ischemia, and finally, currently available clinical trial data. Two valuable lessons learned thus far are that first, rapid induction of hypothermia is key and is best accomplished with a combination of ice-cold saline infusion and the use of endovascular cooling devices, and second, that shivering can be overcome with aggressive anti-shivering protocols including meperidine, buspirone and surface warming. We await the results of clinical trials to determine the utility of therapeutic hypothermia in acute ischemic stroke. If proven efficacious, hypothermia would be a welcome complement to established reperfusion therapies for ischemic stroke patients.
 ...
PMID:Therapeutic hypothermia for acute ischemic stroke. 2039 32

We report the case of a 46-year-old woman presenting with postoperative bilateral cerebral visual loss that was initially misinterpreted as an irreversible ischemic event. Magnetic resonance imaging of the brain showed high signal intensity on T2-weighted and fluid-attenuated inversion recovery images and normal signal intensity on diffusion-weighted images of the posterior lobe, which mostly disappeared with the improvement of clinical symptoms. Subsequent diagnosis revealed posterior reversible encephalopathy syndrome (PRES). Recognition of PRES as the correct diagnosis led to the appropriate management strategy and the recovery of normal vision. Differentiation from acute cerebral ischemia is important in order to prevent permanent vision loss due to delay in initiating prompt and vigorous treatment of exacerbating factors, such as intermittent hypertension. We believe that it is important for anesthesiologists and critical care physicians to accurately diagnose PRES in view of the key differences in the management of similarly presenting conditions.
 ...
PMID:Postoperative blindness associated with posterior reversible encephalopathy syndrome: a case report. 2069 83

The fixed combination containing 5 mg of vinpocetine and 400 mg of pyracetam (vinpotropil) was prescribed to 349 patients with dyscirculatory encephalopathy, I-II stages in dose one capsule three times a day during 3 months. After this treatment, repeated neuropsychological testing showed significant diminishing of dysexecutive cognitive impairment linked with frontal lobes dysfunction. The cognitive improvement was associated with the regress of subjective neurological symptoms like headache, dizziness, tinnitus, fatigue and insomnia. Vinpotropil was safe and well tolerated in elderly patients with chronic cerebral vascular insufficiency.
 ...
PMID:[Vinpotropil in the treatment of dyscirculatory encephalopathy with cognitive impairment without dementia]. 2118 16

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of "Shuigou" (Du 26) and "Baihui" (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0-1.2 mA and 5-20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) "nonoptimal" parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA.
 ...
PMID:Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency. 2183 43

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of severe and permanent neurologic disability after birth. The inducible cyclooxygenase COX-2, which along with COX-1 catalyzes the first committed step in prostaglandin (PG) synthesis, elicits significant brain injury in models of cerebral ischemia; however its downstream PG receptor pathways trigger both toxic and paradoxically protective effects. Here, we investigated the function of PGE(2) E-prostanoid (EP) receptors in the acute outcome of hypoxic-ischemic (HI) injury in the neonatal rat. We determined the temporal and cellular expression patterns of the EP1-4 receptors before and after HIE and tested whether modulation of EP1-4 receptor function could protect against cerebral injury acutely after HIE. All four EP receptors were expressed in forebrain neurons and were induced in endothelial cells after HIE. Inhibition of EP1 signaling with the selective antagonist SC-51089 or co-activation of EP2-4 receptors with the agonist misoprostol significantly reduced HIE cerebral injury 24 h after injury. These receptor ligands also protected brain endothelial cells subjected to oxygen glucose deprivation, suggesting that activation of EP receptor signaling is directly cytoprotective. These data indicate that the G-protein coupled EP receptors may be amenable to pharmacologic targeting in the acute setting of neonatal HIE.
 ...
PMID:Function of prostaglandin E2 EP receptors in the acute outcome of rodent hypoxic ischemic encephalopathy. 2193 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>