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In many neuroinflammatory conditions, including multiple sclerosis (MS), encephalitis, meningitis, brain tumours and cerebral ischaemia, the matrix metalloproteinases (MMPs) play an important role in disrupting the blood-brain barrier (BBB). Normally under tight regulation, increased MMP-9 cerebrospinal fluid levels and excessive proteolytic activity is(More)
BACKGROUND AND PURPOSE Glucocorticoids potently stabilize the blood-brain barrier and ameliorate tissue edema in certain neoplastic and inflammatory disorders of the central nervous system, but they are largely ineffective in patients with acute ischemic stroke. The reasons for this discrepancy are unresolved. METHODS To address the molecular basis for(More)
BACKGROUND AND PURPOSE Loss-of-function mutations of the lipoprotein receptor-related protein-6 (LRP6), a coreceptor in the Wingless-related integration site-β-catenin prosurvival pathway, have been implicated in myocardial ischemia and neurodegeneration. However, it remains to be established whether LRP6 is also involved in ischemic brain injury. We used(More)
Nitric oxide (NO) has emerged as a key mediator in the mechanisms of ischaemic tolerance induced by a wide variety of preconditioning stimuli. NO is involved in the brain protection that develops either early (minutes-hours) or late (days-weeks) after the preconditioning stimulus. However, the sources of NO and the mechanisms underlying the protective(More)
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