Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In bacterial meningitis, long-term neurological sequelae and death are caused jointly by several factors: (1) the systemic inflammatory response of the host, leading to leukocyte extravasation into the subarachnoid space, vasculitis, brain edema and secondary ischemia; (2) stimulation of resident microglia within the CNS by bacterial compounds; and (3) possible direct toxicity of bacterial compounds on neurons. Neuronal injury is mediated by the release of reactive oxygen intermediates, proteases, cytokines and excitatory amino acids, and is executed by the activation of transcription factors, caspases and other proteases. In experimental meningitis, dexamethasone as an adjunct to antibiotic treatment leads to an aggravation of neuronal damage in the hippocampal formation, suggesting that corticosteroids might not be the ideal adjunctive therapy. Several approaches that interfere selectively with the mechanisms of neuronal injury are effective in animal models, including the use of nonbacteriolytic protein synthesis-inhibiting antibiotics, antioxidants and inhibitors of transcription factors, matrix metalloproteinases, and caspases.
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PMID:Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. 1180 37

In spite of improved antimicrobial therapy, bacterial meningitis still results in brain damage leading to significant long-term neurological sequelae in a substantial number of survivors, as confirmed by several recent studies. Meningitis caused by Streptococcus pneumoniae is associated with a particularly severe outcome. Experimental studies over the past few years have increased our understanding of the molecular mechanisms underlying the events that ultimately lead to brain damage during meningitis. Necrotic damage to the cerebral cortex is at least partly mediated by ischemia and oxygen radicals and therefore offers a promising target for adjunctive therapeutic intervention. Neuronal apoptosis in the hippocampus may represent the major pathological process responsible for cognitive impairment and learning disabilities in survivors. However, the mechanisms involved in causing this damage remain largely unknown. Anti-inflammatory treatment with corticosteroids aggravates hippocampal damage, thus underlining the potential shortcomings of current adjuvant strategies. In contrast, the combined inhibition of matrix metalloproteinase and tumour necrosis factor-alpha converting enzyme protected both the cortex and hippocampus in experimental meningitis, and may represent a promising new approach to adjunctive therapy. It is the hope that a more refined molecular understanding of the pathogenesis of brain damage during bacterial meningitis will lead to new adjunctive therapies.
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PMID:Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae. 1201 59

Cranial nerve palsy has a variety of causes such as cerebral ischemia, nerve ischemia in diabetes, infectious and noninfectious meningitis, subarachnoid hemorrhage, malignant tumors of the skull base, neck, or upper mediastinum, aortic aneurysm, surgery of the thyroid,and many more. We report two cases of spontaneous carotid dissections leading to cranial nerve palsies, which is an uncommon cause of isolated cranial nerve palsies.ICA dissection must therefore be included in the differential diagnosis of lower cranial nerve palsy and should be assessed by duplex ultrasound and MRI as is demonstrated in our cases.
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PMID:[Isolated cranial nerve palsy secondary to carotid dissection]. 1259 20

Severe brain damage in patients with pneumococcal meningitis is in part caused by the cytosolic pneumococcal protein pneumolysin. The devastating effect of this neurotoxin might be alleviated by interfering with the cell death pathways that it sets in motion. An important player in these pathways is Bcl-X(L), an antiapoptotic protein of the Bcl-2 family, which is neuroprotective in various in vitro and in vivo models of cell death. We investigated whether its membrane-permeable form, the TAT-Bcl-X(L) fusion protein, is capable of protecting human SH-SY5Y neuroblastoma cells against pneumolysin-induced cell death. Under mild pneumolysin-induced neuronal injury, TAT-Bcl-X(L) increased cell viability significantly by approximately 40% (82.7 +/- 16.1% versus 70.0+/-8.2%; p = 0.04). When the cells were exposed to a more rigorous pneumolysin treatment, TAT-Bcl-X(L) had no protective effects. This suggests the involvement of additional neuronal death pathways in pneumolysin-induced cell death, which are not controlled by Bcl-X(L). Therefore, Bcl-X(L), a promising therapeutic candidate for ischemia and neurodegenerative diseases, is only of partial efficacy in preventing the direct neurotoxicity of pneumolysin.
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PMID:Limited protection of TAT-Bcl-X(L) against pneumolysin-induced neuronal cell death. 1596 Dec 28

Adverse outcome in bacterial meningitis is associated with the breakdown of the blood-brain barrier (BBB). Matrix-metalloproteinases (MMPs) facilitate this process by degradation of components of the BBB. This in turn results in acute complications of bacterial meningitis including edema formation, increased intracranial pressure and subsequent ischemia. We determined the parenchymal balance of MMP-9 and TIMP-1 (tissue inhibitor of MMP) and the structural integrity of the BBB in relation to cortical damage in an infant rat model of pneumococcal meningitis. The data demonstrate that the extent of cortical damage is significantly associated with parenchymal gelatinolytic activity and collagen type IV degradation. The increased gelatinolysis was found to be associated with a brain parenchymal imbalance of MMP-9/TIMP-1. These findings provide support to the concept that MMPs mediated disruption of the BBB contributes to the pathogenesis of bacterial meningitis and that protection of the vascular unit may have neuroprotective potential.
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PMID:In bacterial meningitis cortical brain damage is associated with changes in parenchymal MMP-9/TIMP-1 ratio and increased collagen type IV degradation. 1625 22

Worldwide, about 40 million people are living with HIV and 50 million people have neurocysticercosis (NCC). About 5% of patients with HIV and the majority of patients with NCC develop recurrent seizures. Mechanisms of seizure production in HIV include mass lesions, meningitis, encephalitis, and ischemia. Seizures in NCC may occur at all stages of cyst development, from the vesicular and colloidal to the calcified stages. Seizures in HIV present special problems with regard to choice of antiepileptic drug (AED) and the potential for drug-drug interactions with antiretroviral (ARV) treatments. Newer AEDs with simpler pharmacokinetic profiles may be the preferred agents, particularly when protease inhibitors form part of ARV regimens. Seizures in NCC are easily controlled with the older AEDs. Although there has been some debate about the value of antiparasitic drugs in NCC, accumulating data suggest that the use of these agents in active disease decreases the risk for development of chronic epilepsy.
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PMID:Optimizing therapy of seizures in patients with HIV and cysticercosis. 1719 Sep 16

Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. Experiments using AQP4-null mice provide strong evidence for AQP4 involvement in cerebral water balance. AQP4-null mice are protected from cellular (cytotoxic) brain edema produced by water intoxication, brain ischemia, or meningitis. However, AQP4 deletion aggravates vasogenic (fluid leak) brain edema produced by tumor, cortical freeze, intraparenchymal fluid infusion, or brain abscess. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 deletion also worsens obstructive hydrocephalus. Recently, AQP4 was also found to play a major role in processes unrelated to brain edema, including astrocyte migration and neuronal excitability. These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury.
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PMID:Aquaporin-4 and brain edema. 1734 37

Ultrasound provides a diagnostic modality that allows a whole-body approach at the bedside of a critically ill patient in the search for infectious foci. Both common sites of infection, such as the lung and pleura, central veins, and maxillary sinuses, and also less common sites, such as gastrointestinal perforation, sepsis due to mesenteric ischemia, or even meningitis, provide characteristic ultrasound patterns. Optimal use of ultrasound also combines bedside diagnosis with subsequent interventional procedures that can decrease the need for transfer to other imaging and interventional suites. Experience has shown that fevers of unknown origin in the critical care unit often have ultrasound equivalents. Thus, if a comprehensive ultrasound examination is negative, it is now appropriate to speak of fever of unknown sonographic origin.
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PMID:Point-of-care ultrasound: Infection control in the intensive care unit. 1744 86

The serum uric acid (UA) levels were measured in 112 patients with multiple sclerosis (MS) and 794 patients with different types of other neurological diseases (OND) or healthy control group. Serum UA levels, along with relevant clinical parameters of MS and OND, were also investigated. MS patients had significantly lower UA levels than those with transient ischemia attack (344.6 +/- 130.6 micromol/L, P = 0.000), cerebral hemorrhage (311.9 +/- 104.7 micromol/L, P = 0.000), cerebral infarction (291.3 +/- 101.6 micromol/L, P = 0.014) and the healthy control group (312.1 +/- 92.8 micromol/L, P = 0.000). MS patients had significantly higher serum UA levels than those with cryptococcus meningitis or meningoencephalitis (178.9 +/- 107.0 micromol/L, P = 0.000) and tuberculous meningitis or meningoencephalitis patients (175.7 +/- 99.9 micromol/L, P = 0.000). There were no significant differences in UA levels between patients with MS and those with facial neuritis, viral meningitis or encephalitis, pulmonary tuberculosis, polymyositis or dermatomyositis, myasthenia gravis, subarachnoid hemorrhage, migraine, Guillain-Barre syndrome and myelitis. In addition, UA levels were independently correlated with gender and duration of MS, but neither with MRI activity, disability nor subtypes of the disease in MS patients. Our data suggest that UA has two biphasic functions: neuroprotective and injurious. Our studies may help physicians to deal with conditions having abnormal UA levels.
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PMID:Serum uric acid levels of patients with multiple sclerosis and other neurological diseases. 1794 20

Proinflammatory cytokines and chemokines have been implicated in the pathogenesis of several neurological and neurodegenerative disorders. Prominent among such factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-alpha. Under normal physiological conditions, TNF-alpha orchestrates a diverse array of functions involved in immune surveillance and defense, cellular homeostasis, and protection against certain neurological insults. However, paradoxical effects of this cytokine have been observed. TNF-alpha is elicited in the brain following injury (ischemia, trauma), infection (HIV, meningitis), neurodegeneration (Alzheimer's, Parkinson's), and chemically induced neurotoxicity. The multifarious identity for this cytokine appears to be influenced by several mechanisms. Among the most prominent are the regulation of TNFalpha-induced NF-kappaB activation by adapter proteins such as TRADD and TRAF, and second, the heterogeneity of microglia and their distribution pattern across brain regions. Here, we review the differential role of TNF-alpha in response to brain injury, with emphasis on neurodegeneration, and discuss the possible mechanisms for such diverse and region-specific effects.
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PMID:Divergent roles for tumor necrosis factor-alpha in the brain. 1804 Aug 39


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