07 October 2010

E-selectin a vaccine for stroke..


Research had been done to show that tolerance to E-selectin in rats can have a preventative and protective effects on ischemic stroke. But can this research lead to a possible vaccine against stroke in humans? E- selectin is a cytokine inducible adhesion molecule that is expressed when the endothelium is activated by inflammatory stimuli such as IL1 or tumor necrosis factor. In the research article “Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury,” the researchers investigated wether E-selectin tolerance in spontaneously hypertensive-genetically stroke prone rats could decrease ischemic stoke injury. They suggested that E-selectin tolerance could lead to redirecting regulatory T-cells to activating blood vessels and releasing anti-inflammatory factors and thereby decreasing stoke injury.


To support this, the researchers created 7 groups of SRH-SP rats. The first two groups were the control single and booster groups, given PBS. The next two groups were the single and booster active tolerization groups that were given E-selectin intranasaly. The last three groups were the adaptive tolerization groups that were given cells from the active groups. The single tolerization groups were given E-selecting every other ay for 10 days and the booster groups followed the same schedule but it was repeated after 11 days. After tolerization, the middle cerebral artery was surgically occluded and 6 to 48 hours later the rats were killed to be examined.


As a result, they found that infract volume was significantly decreased in booster rats, but not much in single tolerization group and no difference was found in the PBS control groups. In the active booster group, a 45% decrease was observed and in the adoptive booster groups a 35% decrease was found. They also found an increased concentration of IL 10, an anti-inflammatory factor released by T cells. Since the same effect was found in active and adoptive groups, it supports the idea at this protection is most likely cells mediated.


This and other studies shows that tolerizing for E-selectin can have a protective effects after stroke in rats but claiming it to be a possible vaccination for stroke is a far stretch. First, this study is done on rats and a human study may not have the same results. This time of tolerance is very difficult to create in humans and therefore this would not be successful. Also, this type of intervention that takes place before a stroke has occurred is hard to implement since we do not normally know who and when a person is going to have a stroke. More research needs to be done to establish effects of this therapy in humans.

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