ABSTRACT
Matrix metalloproteinases (MMPs) are involved in remodelling extracellular matrix. Gelatinase B (MMP-9) is an inducible 92 kDa MMP expressed by neutrophils, microglia, and endothelial cells. Gelatinase A (MMP-2) is a 72 kDa MMP, constitutively expressed in brain. Elevated MMP activity has been linked to various pathologic conditions, and the therapeutic benefit of MMP inhibitors is under study in a few experimental models. Using gelatin zymography, we have compared activities of these MMPs in infarcted and matched non-infarcted cerebral tissue from eight subjects dying at intervals of less than 2 h to several years after a stroke. Gelatinase B activity was markedly elevated in the infarcted tissue at two days post-infarction, and remained elevated in cases dying months after the event. Increases in gelatinase A activity were subtle at 2-5 days; they were marked and significant in cases dying at 4 months and later. The findings indicate distinct temporal profiles of post-ischemic gelatinase activity in human brain, with earlier but equally persistent elevation in gelatinase B when compared to gelatinase A.
Subject(s)
Brain Ischemia/enzymology , Collagenases/metabolism , Gelatinases/metabolism , Metalloendopeptidases/metabolism , Aged , Aged, 80 and over , Female , Humans , Male , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Middle Aged , Time FactorsABSTRACT
Previous studies have shown a marked decline in neuronal and an increase in glial gene expression in Alzheimer's disease (AD) neocortex. Severity of pathologic changes may be greater in presenile AD (PAD) than in senile AD (SAD). We evaluated whether changes in transcript expression were altered as a function of age or pathologic severity. Northern analysis revealed a marked (> 50%) decline in expression of transcripts for the neurofilament light subunit and the major amyloid precursor protein (APP) isoforms in both PAD and SAD. Expression of these neuronal transcripts declined as a function of age in AD and control cases. Expression of the glial fibrillary acidic protein (GFAP) transcript was increased in AD, particularly in the presenile group. AD cases with larger numbers of neurofibrillary tangles had higher levels of GFAP transcript; AD cases with larger numbers of senile plaques had higher levels of APP695 transcript. We conclude that the neuronal mRNA decrements of AD are superimposed on an age-related decline. Age-related shift in expression of certain genes may account for the differences in pathologic severity of PAD and SAD.
