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The capacity of minocycline to alleviate disease for several neurological disorders in animals is increasingly being recognised. Indeed, that one drug alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is astounding. In this review, we(More)
Myelination, the process in which oligodendrocytes coat CNS axons with a myelin sheath, represents an important but poorly understood form of neural plasticity that may be sexually dimorphic in the adult CNS. Remission of multiple sclerosis during pregnancy led us to hypothesize that remyelination is enhanced in the maternal brain. Here we report an(More)
Acute spinal cord injury (SCI) produces tissue damage that continues to evolve days and weeks after the initial insult, with corresponding functional impairments. Reducing the extent of progressive tissue loss ('neuroprotection') following SCI should result in a better recovery from SCI, but treatment options have thus far been limited. In this study, we(More)
The phospholipase A(2) (PLA(2)) superfamily hydrolyzes phospholipids to release free fatty acids and lysophospholipids, some of which can mediate inflammation and demyelination, hallmarks of the CNS autoimmune disease multiple sclerosis. The expression of two of the intracellular PLA(2)s (cPLA(2) GIVA and iPLA(2) GVIA) and two of the secreted PLA(2)s(More)
Multiple sclerosis is characterized by the infiltration of leukocytes into the CNS. As matrix metalloproteinases (MMPs) facilitate the passage of leukocytes across matrix barriers, we tested the hypothesis that targeting MMPs could attenuate neuro-inflammation. We report that minocycline, a widely used generic drug with a good safety record, inhibited MMP(More)
Matrix metalloproteinases (MMPs) are implicated in multiple sclerosis where one of their roles may be to facilitate the transmigration of circulating leukocytes into the CNS. Studies have focused on only a few MMPs, and much remains unknown of which of the 23 MMP family members is/are critical to the multiple sclerosis disease process. Using quantitative(More)
Interferon-beta and glatiramer acetate (GA) are the two main groups of drugs used in the treatment of MS. Notably, while both ultimately decrease CNS inflammation, they do so by very different mechanisms. Interferon-beta has potent activity at the blood-brain barrier and impairs the trafficking of inflammatory cells into the CNS. In contrast, GA has(More)
Preclinical studies have attributed neuroprotective properties to the antibiotic minocycline. Animal studies and early clinical trials support its use in several neurological diseases. In animal spinal cord injury models, minocycline improved neurological and histological outcomes, reduced neuronal and oligodendroglial apoptosis, decreased microglial(More)
The objective of the current study was to investigate whether minocycline improves the effect of an existing multiple sclerosis (MS) medication, interferon-beta, on experimental autoimmune encephalomyelitis (EAE) in mice. When used at sub-optimal doses, neither medication affected EAE but their combination at these doses led to the significant alleviation(More)
Remyelination is a critical repair process that is initiated after a demyelinating insult. The failure to remyelinate contributes to neurological diseases such as multiple sclerosis. Here, we test the hypothesis that proteinase activity is required for the extensive remodeling of the extracellular matrix that occurs during remyelination. We show that mice(More)