Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Japanese neuropathologists have accomplished and contributed to a considerable number of achievements, and some of these are cited in other articles in this issue. Several of these achievements as well as other miscellaneous discoveries are briefly summarized in the present paper. Specifically these relate to rabies postvaccinal encephalomyelitis, experimental allergic encephalomyelitis, brain tumor research, neuromuscular disorders, schizophrenia, viral infections, glial inclusion body in multiple system atrophy, and the neurobiology of glia.
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PMID:Encephalomyelitis, brain tumors, neuromuscular diseases and miscellaneous disorders. 1103 80

Glia form a cellular network consisting mainly of astrocytes that nourish the neurons, oligodendrocytes that form myelin, and microglia that ensure the immunological defence of the nervous system. Experimental allergic encephalomyelitis is an animal model of multiple sclerosis, characterised by cellular infiltrates and demyelinisation in the central nervous system. It can be induced in susceptible rats (DA) by inoculation of foreign protein. Other, non-susceptible rats (AO) have infiltrates that disappear without functional signs of disease. We have found microglia and astrocytes in infiltrates 10 days after inoculation. At 14 days they are even more marked in the DA, but astrocytosis is less in the AO. Microglia have disappeared at 14 days in the DA, but persist in the AO. We suggest that the infiltrates are dispersed by microglial activity that persists in the AO and prevents astrocytosis. In the DA the loss of microglia allows gliosis to occur, with demyelination due to lesions of oligodendrocytes, and clinical signs. We have also studied astrocytes and microglia in the cerebral cortex of schizophrenics and control non-schizophrenics. The number of astrocytes does not vary between patients and controls, but microglia are more numerous in the patients. We conclude that there is a cortical microgliosis in schizophrenia that may be a response to an earlier lesion, perhaps protecting neighbouring neurons.
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PMID:[Role of neuroglia in central nervous system diseases]. 1513 3

The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters. New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented. Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism.
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PMID:Glutamate in CNS disorders as a target for drug development: an update. 1561 69

Calcium-activated potassium channels modulate calcium signaling cascades and membrane potential in both excitable and non-excitable cells. In this article we will review the physiological properties, the structure activity relationships of the existing peptide and small molecule modulators and the therapeutic importance of the three small-conductance channels KCa2.1-KCa2.3 (a.k.a. SK1-SK3) and the intermediate-conductance channel KCa3.1 (a.k.a. IKCa1). The apamin-sensitive KCa2 channels contribute to the medium afterhyperpolarization and are crucial regulators of neuronal excitability. Based on behavioral studies with apamin and on observations made in several transgenic mouse models, KCa2 channels have been proposed as targets for the treatment of ataxia, epilepsy, memory disorders and possibly schizophrenia and Parkinson's disease. In contrast, KCa3.1 channels are found in lymphocytes, erythrocytes, fibroblasts, proliferating vascular smooth muscle cells, vascular endothelium and intestinal and airway epithelia and are therefore regarded as targets for various diseases involving these tissues. Since two classes of potent and selective small molecule KCa3.1 blocker, triarylmethanes and cyclohexadienes, have been identified, several of these postulates have already been validated in animal models. The triarylmethane ICA-17043 is currently in phase III clinical trials for sickle cell anemia while another triarylmethane, TRAM-34, has been shown to prevent vascular restenosis in rats and experimental autoimmune encephalomyelitis in mice. Experiments showing that a cyclohexadiene KCa3.1 blocker reduces infarct volume in a rat subdural hematoma model further suggest KCa3.1 as a target for the treatment of traumatic and possibly ischemic brain injury. Taken together KCa2 and KCa3.1 channels constitute attractive new targets for several diseases that currently have no effective therapies.
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PMID:Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. 1758 55

Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.
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PMID:Altered lipid metabolism in brain injury and disorders. 1875 14

Anti-N-methyl-D-aspartate-receptor (NMDA-R) encephalitis is a new autoimmune, often paraneoplastic disorder that presents with complex neuropsychiatric symptoms. It was first described in 2007 by Dalmau et al. Our patient presented with headache, behavioral changes and then seizures with hallucinations. She was initially misdiagnosed to have schizophrenia and was prescribed antipsychotics. She deteriorated and developed further seizures with hypoventilation and choreoathetosis. Her blood investigations were positive for mycoplasma IGM. Her CSF studies showed high white cell counts, predominantly lymphocytes, and high anti-NMDA-R titre. Her brain MRI scans showed high tbl2 and FLAIR intensities in the grey and white matter of the left cerebellar hemisphere suggestive of acute disseminated encephalomyelitis. She responded to treatment with antibiotics, multiple antiepileptics, steroids and needed five sessions of plasmapheresis. There was no underlying malignancy on repeated scanning of the abdomen. She needed around one year for full recovery with intensive rehabilitation. The objective of this paper was to highlight the occurrence of this fairly new, challenging, easily missed, not-so-rare form of encephalitis often occurring in the absence of fever.
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PMID:First Bahraini adolescent with anti-NMDAR-Ab encephalitis. 2653 70

Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration.
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PMID:Design and Efficacy of Nanogels Formulations for Intranasal Administration. 2978 6

The atypical antipsychotic agent, clozapine, is used to treat a variety of neurological disorders including schizophrenia and Parkinson's disease and readily crosses the blood brain barrier to interact with a wide range of neuroreceptors including those for dopamine and serotonin. Recent work has shown that clozapine can reduce neuroinflammation in experimental autoimmune encephalomyelitis, a neuroinflammatory model of multiple sclerosis (MS) and mediates its effects in the central nervous system. To further characterise the protection provided by clozapine, the cuprizone model of demyelination was used to assess the effect of clozapine treatment on the cellular events surrounding demyelination and remyelination. Using this model of non-immune demyelination, we found that clozapine administration was unable to prevent demyelination, but when administered post demyelination, was able to enhance the rate of functional recovery. The more rapid improvement of clozapine-treated mice correlated with a decreased level of astrocyte and microglial activation but only modestly enhanced remyelination. Together, these studies highlight the potential of clozapine to support enhanced functional recovery after demyelination, such as that occurring during MS.
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PMID:Clozapine administration enhanced functional recovery after cuprizone demyelination. 3107 Nov 2