Biomedical subjects

Terence Smith

Publications and source records attributed to Terence Smith.

3 recordsLinked to original sources

PubMed2005

ADAM-17 and TIMP3 protein and mRNA expression in spinal cord white matter of rats with acute experimental autoimmune encephalomyelitis.

Tumour necrosis factor (TNF) is a major immunomodulatory and proinflammatory cytokine implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). ADAM-17 cleaves membrane-bound TNF into its soluble form. The distribution and level of ADAM-17 expression within spinal cords of Lewis rats with EAE was investigated. ADAM-17 was associated with endothelial cells in the naïve and pre-disease spinal cords. In peak disease astrocytic and inflammatory cells expressed ADAM-17. Upregulation of ADAM-17 mRNA expression was coupled with a decrease in mRNA levels of its inhibitor TIMP3 suggesting a role for ADAM-17 in EAE pathogenesis.

ADAM Proteins↗

PubMed2003

Multiple sclerosis and glutamate.

Experimental autoimmune encephalomyelitis reproduces in rodents the features of multiple sclerosis, an immune-mediated, disabling disorder of the human nervous system. No adequate therapy is available for multiple sclerosis, despite anti-inflammatory, immunosuppressive, and immunomodulatory measures. Increasingly glutamate is implicated in the pathogenesis of neurodegenerative diseases. Here we (1) review changes in the glutamatergic system in multiple sclerosis and (2) reveal the effects of glutamate AMPA antagonists in acute and chronic rodent models of multiple sclerosis. Administration of structurally diverse competitive and non-competitive AMPA antagonists reduces neurologic disability in rodents subjected to acute experimental autoimmune encephalomyelitis. In addition, AMPA antagonists are active in both the adoptive transfer and in chronic models of experimental autoimmune encephalomyelitis in rats and mice and affect both the acute and chronic relapsing phases. Moreover, short-term therapy with AMPA antagonists leads to sustained benefit well into the progressive phases. These results imply that therapeutic strategies for multiple sclerosis should be complemented by glutamate AMPA antagonists to reduce neurologic disability.

Animals↗

PubMed2002

Altered expression of glutamate transporters in experimental autoimmune encephalomyelitis.

Amelioration of experimental autoimmune encephalomyelitis (EAE) by blockade of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), has been recently demonstrated [Nat. Med. 6 (2000) 67; Nat. Med. 6 (2000) 62]. However, the mechanisms underlying regulation of the extracellular glutamate concentration in EAE are unclear. To address this, we examined the expression of three distinct Na(+)-dependent glutamate transporters (GLT-1, GLAST and EAAC1) in the spinal cord of the Lewis rat EAE. EAE induced a dramatic increase in EAAC1 protein and mRNA levels, which corresponded closely with the course of neurological symptoms. In contrast, the levels of GLT-1 and GLAST protein were down-regulated in the spinal cord at the peak of disease symptoms, and no recovery was observed after remission. Furthermore, these changes in GLT-1, GLAST and EAAC1 expression were suppressed by treatment with NBQX. These results suggest that AMPA receptor activation precedes the altered expression of glutamate transporters, and that the dysregulation of extracellular glutamate concentration might play a critical role in pathological changes and neuronal dysfunction in EAE.

Amino Acid Transport System X-AG↗