Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature from embolic focal cerebral ischemia

I don't really understand so go straight to your doctor about its usefulness for your next stroke. 

Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature from embolic focal cerebral ischemia

Cui J¹, Chen S, Zhang C, Meng F, Wu W, Hu R, Hadass O, Lehmidi T, Blair GJ, Lee M, Chang M, Mobashery S, Sun GY, Gu Z.

Author information

Abstract

BACKGROUND:

Cerebral ischemia has been shown to induce activation of matrix metalloproteinases (MMPs), particularly MMP-9, which is associated with impairment of the neurovasculature, resulting in blood-brain barrier breakdown, hemorrhage and neurodegeneration. We previously reported that the thiirane inhibitor SB-3CT, which is selective for gelatinases (MMP-2 and -9), could antagonize neuronal apoptosis after transient focal cerebral ischemia.

RESULTS:

Here, we used a fibrin-rich clot to occlude the middle cerebral artery (MCA) and assessed the effects of SB-3CT on the neurovasculature. Results show that neurobehavioral deficits and infarct volumes induced by embolic ischemia are comparable to those induced by the filament-occluded transient MCA model. Confocal microscopy indicated embolus-blocked brain microvasculature and neuronal cell death. Post-ischemic SB-3CT treatment attenuated infarct volume, ameliorated neurobehavioral outcomes, and antagonized the increases in levels of proform and activated MMP-9. Embolic ischemia caused degradation of the neurovascular matrix component laminin and tight-junction protein ZO-1, contraction of pericytes, and loss of lectin-positive brain microvessels. Despite the presence of the embolus, SB-3CT mitigated these outcomes and reduced hemorrhagic volumes. Interestingly, SB-3CT treatment for seven days protected against neuronal laminin degradation and protected neurons from ischemic cell death.

CONCLUSION:

These results demonstrate considerable promise for the thiirane class of selective gelatinase inhibitors as potential therapeutic agents in stroke therapy.

Potential treatment could prevent brain damage after strokes

I discussed this on May 18 here:
http://oc1dean.blogspot.com/2012/05/nih-funded-research-provides-new-clues.html
http://www.expatriatehealthcare.com/News/Expatriate_Health_Insurance_News_Potential_treatment_could_prevent_brain_damage_after_strokes683
A compound is being studied by international healthcare experts at the University of Missouri (MU) and the University of Notre Dame that could potentially prevent people who have suffered from a stroke from sustaining brain damage, as well as reduce the amount of harm the incident causes.

The research, which is outlined in the journal Molecular Neurodegeneration, involves the analysis of a thiirane class of gelatinase selective inhibitors and how these function on a matrix metalloproteinase enzyme (MMP), especially a substance known as MMP-9, which is known to play a role in a number of important pathological events that occur following traumatic brain injuries or similar events.

MU School of Medicine assistant professor of pathology and anatomical sciences and corresponding author of the article Zezong Gu said the inhibitors might be combined with a tissue plasminogen activator to give people who have suffered a stroke a "longer window of time to receive emergency treatment".

He pointed out that "time is a matter of life and death" for people who have had a stroke, echoing the advice of the UK's National Health Service, which says "immediate medical attention" is needed when a person begins showing signs of this condition.

"MMPs play a role in the structure of blood vessels in the brain and are also needed in the interactions between cells during development and tissue remodelling," the researcher declared.

Mr Gu stated that without regulation, these enzymes can contribute to stroke.

He suggested that the gelatinase selective inhibitor could protect the blood vessels from MMP-9's damaging effects, while preventing damage to neurons.

In 2005, the scientist had previously played the role of lead author on a study published in the Journal of Neuroscience that had revealed MMP-9 could be a promising area that therapeutic medicines for stroke patients could target.

"We are still in the research phase for this type of compound," Mr Gu declared.