Here we describe the spatio-temporal distribution of activated MMP-2 and MMP-9 in the brain of rats subjected to 2 h middle cerebral artery occlusion (MCAo) followed by different periods of reperfusion (15 min, 2 h, 6 h and 22 h). By in situ zymography we have observed that gelatinases become activated 15 min and 2 h after the beginning of reperfusion in the ischemic core and
In situ zymography signal broadly co-localized with NeuN-positive cells, thus suggesting that proteolysis mainly occurs in neurons. Gelatinolytic activity was mainly detected in cell nuclei, marginally appearing in the cytosol only at later selleck screening library stages following the insult; we did not detect variations in gelatinolysis in the extracellular matrix. Finally, we report that pharmacological inhibition of MMPs by N-[(2R)-2-(hydroxamidocarbonyl-methyl)-L-methylpenthanoyi]-L-tryptophan methylamide (GM6001) significantly Stem Cells & Wnt inhibitor reduces brain infarct volume induced
by transient MCAo. Taken together our data underscore the crucial role of gelatinases during the early stages of reperfusion and further extend previous observations documenting the detrimental role of these enzymes in the pathophysiology of brain ischemia. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We develop a genetic algorithm (GA) approach to a selleck kinase inhibitor well-known model of vigilance behaviour in a group of animals. We first demonstrate that the GA approach can provide a good match to analytic solutions to the original model. We demonstrate that
a GA can be used to find the evolutionarily stable strategies in a model relevant to behavioural ecology where the fitness of each strategy is determined by the frequencies of different strategies in the population. We argue that the GA implementation demonstrates the combination of assumptions used to generate analytic solution to the original model can only be simultaneously satisfied under relatively restrictive conditions on the ecology of the species involved; specifically that group membership is very fluid but group size is conserved over timescales of individual foraging bouts. We further explore the sensitivity of model predictions to alternative choices in the implementation of the GA, and present advice for implementation and presentation of similar models. In particular, we emphasise the need for care in measuring the predictions of such models, so as to capture the intrinsic behaviour of the system and not the remnant of often arbitrarily chosen initial conditions. We also emphasise the potential for GA models to be more transparent about model assumptions regarding underlying biology than analytic models. (c) 2007 Elsevier Ltd. All rights reserved.