Glutamate excitotoxicity is implicated in the progressive loss of oligodendrocytes in multiple sclerosis, but how glutamate metabolism is dysregulated in the disease remains unclear. Because there is microglia activation in all stages of multiple sclerosis, we determined whether a microglia product, interleukin-1beta, could provide the mechanism for glutamate excitotoxicity. We found that whereas interleukin-1beta did not kill oligodendrocytes in pure culture, it produced apoptosis of oligodendrocytes in coculture with astrocytes and microglia. This requirement for a mixed glia environment suggests that interleukin-1beta impairs the well-described glutamate-buffering capacity of astrocytes. In support, antagonists at AMPA/kainate glutamate receptors, NBQX and CNQX, blocked the interleukin-1beta toxicity to oligodendrocytes. Another microglia/macrophage cytokine, tumor necrosis factor-alpha, also evoked apoptosis of oligodendrocytes in a mixed glia environment in an NBQX-blockable manner. These results provide a mechanistic link between the persistent and insidious microglia activation that is evident in all stages of multiple sclerosis, with the recent appreciation that glutamate excitotoxicity leads to the destruction of oligodendrocytes in the disease.

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Pergolide is an ergot-derived dopamine agonist used in the treatment of Parkinson's disease (PD). Like other ergot derivatives, pergolide can be associated with fibrotic complications, including cardiac valvulopathy. Recent reports have indicated that these valvular changes may occur more commonly than initially recognized. The present case demonstrates how rapidly these changes can evolve in the setting of pergolide treatment. CASE REPORTA 61-year-old woman was admitted with a one year history of progressive dyspnea. There was no previous history of heart disease or other significant medical problems, except for PD diagnosed about seven years previously. At that time she was started on levodopa/carbidopa, which produced good symptom control for about three years, until end-of-dose deterioration developed. Pergolide was added and proved successful in regaining control of her Parkinson's symptoms. Parkinson's disease medications at the time of hospital admission consisted of controlled release levodopa/carbidopa 200/50, 1.5 tablets four times daily, and pergolide 1.75mg four times daily.Examination revealed a thin, anxious woman with signs of congestive heart failure, including a Grade III/VI pansystolic murmur ABSTRACT: Background: A 61-year-old woman with Parkinson's disease, receiving pergolide 1.75 mg four times daily, was admitted with progressive dyspnea. Methods: Investigations revealed mitral and aortic regurgitation. She underwent surgical mitral replacement and aortic repair, but had a postoperative course characterized by repeated bouts of congestive heart failure. Results: Severe tricuspid valve (TV) regurgitation developed within one month after the TV was reported on echocardiography to be relatively normal. Subsequent discontinuation of pergolide was associated with symptomatic improvement. Conclusions: This case illustrates the severity and rapidity with which cardiac valvular abnormalities can develop in patients receiving pergolide. CASE REPORTinvolving the entire precordium, and evidence of pulmonary and peripheral edema. There was mild symmetrical cogwheel rigidity in upper limbs, slight resting tremor of both hands, and bradykinesia for repetitive finger movements. In general, PD signs seemed well controlled.Cardiac investigations included transesophageal echocardiogram (TEE), which confirmed the presence of severe mitral valve (MV) regurgitation and moderate aortic valve (AV) insufficiency. The pulmonary and tricuspid valves (TV) were relatively normal, although mild TV regurgitation was noted. Surgical AV repair and MV replacement were undertaken, with the MV replaced by a mosaic bioprosthetic tissue valve. Intra-operatively, significant thickening of all https://www.cambridge.org/core/terms. https://doi