The same enzymes that cause brain damage following an acute attack of stroke could be beneficial some time later. This finding perhaps highlights that effective treatment of stroke could be possible if administered few weeks following the stroke, instead of the treatment within couple of hours following stroke. Additionally, it could open avenues for the development of novel stroke treatment strategies and new generation drugs in treating the same.
The enzyme matrix metalloproteinase-9 (MMP-9) has been found to help in remodeling of the brain 14 days following stroke, in experiments conducted on animal mouse models by Harvard medical school researchers. The results of the study can be found in April issue of the Nature Medicine journal.
The enzymes serve to breakdown the complex structure that surrounds the cells, known as the extracellular matrix. The compound has been found to result in growth of new blood vessel in the damaged brain region. In addition it induces cell growth, cell differentiation and movement of the cells.
Stroke occurs due to a temporary loss of blood supply to the brain. This can occur either due to blockage of a blood vessel though blood clot or rupture of a blood vessel, supplying the brain. Following stroke, MMPs eat away the damaged brain tissue, increasing risk of inflammation and brain hemorrhage.
Current treat of stroke is directed at inhibiting the effect of these damage-causing MMPs. The only FDA-approved medication for the treatment of stroke is tissue plasminogen activator (tPA). This has to be administered with three hours of an acute stroke episode, to prevent irreversible damage to the brain.
Rats that were designed to mimic human models of stroke were given different doses of the MMP inhibitor, at different intervals. Administration of the inhibitor immediately following the stroke showed smaller brain damaged areas. No effect was observed when it was administered three days following stroke. Extensive brain damage was seen when the inhibitor was given at 7 or 14 days after stroke.
Surprisingly, high levels of the MMPs were found adjacent to the damaged area, more specifically in the peri-infarct cortex, an area that enables recovery of the brain following stoke.
'We have mostly thought of MMPs as being bad. Our data strongly suggest that they play a totally different role during stroke recovery. The peri-infarct zone is very dynamic and potentially very malleable for long periods of time after stroke,' said Eng H. Lo, from the Neuroprotection Research Laboratory at Massachusetts General Hospital.
The researchers have however warned about the use of these compounds in stroke management, as the activity of the MMPs has to be regulated to ensure an optimal recovery of the stroke patient.