Matrix metalloproteinase inhibition counteracts impairment of cortical experience-dependent plasticity after photothrombotic stroke.

Abstract

Matrix metalloproteinases (MMPs) are fine modulators of brain plasticity and pathophysiology. The inhibition of MMPs shortly after ischaemic stroke reduces the infarct size and has beneficial effects on post-stroke behavioural recovery. Our previous studies have shown that photothrombotic cortical stroke disrupts use-dependent plasticity in the neighbouring cortex. The aim of the present study was to check whether the inhibition of MMPs after photothrombosis rescued the plastic capacity of the barrel cortex. To induce plasticity in adult mice, a unilateral deprivation of all vibrissae except row C was applied. The deprivation started immediately after stroke and lasted 7 days. This procedure, in control (non-stroke) animals, results in an enlargement of functional representation of the spared row, as shown with [(14)C]2-deoxyglucose uptake mapping. In mice with stroke induced by photothrombosis in the vicinity of the barrel cortex, vibrissae deprivation did not result in an enlargement of the cortical representation of the spared row C of vibrissae, which confirmed our previous results. However, when mice were injected with the broad-spectrum inhibitor of MMPs FN-439 (10 mg/kg, i.v.) immediately before a stroke, an enlargement of the representation of the spared row similar to the enlargement found in sham mice was observed. These results indicate the involvement of MMPs in the impairment of use-dependent plasticity in the vicinity of an ischaemic lesion.

• Authors: A Cybulska-Klosowicz, M Liguz-Lecznar, D Nowicka, M Ziemka-Nalecz, M Kossut, J Skangiel-Kramska
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 33 Issue 12 Pg. 2238-46 (Jun 2011) ISSN: 1460-9568 [Electronic] France
• PMID: 21615560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Chemical References

• 4-aminobenzoyl-glycyl-prolyl-leucyl-alanine hydroxamic acid
• Carbon Radioisotopes
• Hydroxamic Acids
• Matrix Metalloproteinase Inhibitors
• Oligopeptides
• Deoxyglucose
• Matrix Metalloproteinases

Topics

• Animals
• Autoradiography
• Brain Mapping (methods)
• Carbon Radioisotopes
• Deoxyglucose
• Hydroxamic Acids (pharmacology)
• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinases (metabolism, physiology)
• Mice
• Mice, Inbred C57BL
• Neuronal Plasticity (drug effects, physiology)
• Oligopeptides (pharmacology)
• Radionuclide Imaging
• Sensory Deprivation (physiology)
• Somatosensory Cortex (diagnostic imaging, metabolism, physiopathology)
• Stroke (diagnostic imaging, metabolism, physiopathology)
• Vibrissae (physiology)