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

Memantine, a clinically employed drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rat experimental autoimmune encephalomyelitis (EAE). Interestingly, this therapeutic effect was not due to dampened CNS inflammation, as assessed by immunohistochemical evaluation of spinal cord tissue. Furthermore, numbers of interferon gamma (IFN gamma) mRNA expressing cells were not decreased, as assessed by in situ hybridization. Systemic immunity in terms of numbers of IFN gamma secreting cells in response to immunodominant myelin basic protein (MBP) peptides ex vivo was not reduced, and non-toxic doses of memantine did not affect lymphocyte proliferation or IFN gamma secretion in vitro. Considering these findings, we hypothesize that effector mechanisms responsible for reversible neurological deficits in EAE may involve NMDA receptors, and this highlights neurons as targets during autoimmune neuroinflammation.
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PMID:Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis. 878 60

Previous studies by us have strongly indicated a role for the N-methyl-D-aspartate (NMDA) receptor in the pathogenesis of experimental allergic encephalomyelitis (EAE) and, moreover, the loss of blood-brain barrier (BBB) integrity implicit in the disease. The current investigation has used the NMDA receptor antagonist memantine to modify the neurological course of EAE and, in particular, prevent BBB breakdown. Memantine was administered orally either semiprophylactically, from day 7 postinoculation (PI), or therapeutically, 10 to 11 days PI. Semiprophylactic administration of drug at 60 mg/kg b.wt. significantly restored BBB integrity, reduced symptoms, and limited inflammatory lesions (p < 0.05), when assessed 12 days PI. Higher concentrations of memantine did not notably advance disease improvements observed at 60 mg/kg b.wt., and 40-mg/kg b.wt. doses only reduced histological scores (p < 0.05). Therapeutic application of memantine was found to be as effective as semiprophylactic dosing. Administration of drug at 60 mg/kg b.wt. was demonstrated as the optimum dose, significantly reducing disease, BBB permeability, and lesions (p < 0.01). Extended studies revealed that, after cessation of memantine treatment using either dosing regime, any subsequent appearance of disease was suppressed in severity and duration. We have provided further strong evidence in support of a role for the NMDA receptor in the development of EAE and, in particular, the loss of BBB function and recruitment of inflammatory cells. Moreover, memantine is therapeutically efficacious, suggesting the NMDA receptor as a viable pharmacological target for future treatment of human neurological conditions such as multiple sclerosis.
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PMID:Modulation of blood-brain barrier dysfunction and neurological deficits during acute experimental allergic encephalomyelitis by the N-methyl-D-aspartate receptor antagonist memantine. 1206 99

We compared preventive and therapeutic effects of memantine, a selective blocker of NMDA-receptors, and IEM-1966, a blocker of both NMDA- and GluR1 AMPA-receptors, on the model of acute experimental allergic encephalomyelitis. Memantine in high doses prevented the development of experimental allergic encephalomyelitis only in 10% rats, slightly (by 1.4-1.5 times) moderated the neurological disturbances, and shortened the duration of the disease. In far lower doses, IEM-1966 prevented the development of experimental allergic encephalomyelitis in 50% rats, while in the affected rats it decreased the severity of neurological disturbances and duration of the disease by 3-4 times. When applied during the clinical phase of the disease, IEM-1966 decreased the severity of neurological disturbances and duration of the disease by 2.0-2.5 times predominantly in rats with mild and moderate course of experimental allergic encephalomyelitis.
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PMID:Comparative study of preventive and therapeutic effects of IEM-1966 and memantine in rats with experimental allergic encephalomyelitis. 1839 84