October 2011

aB cristallin (Cryab), a member of the small heat shock proteins family displays both anti-apoptotic and immunomodulatory properties, and is abundantly expressed in response to brain insults such as in the case of stroke and multiple sclerosis. In this study, Cryab / mice were exposed to 30 min of middle cerebral artery occlusion. An increased lesion size and diminished neurologic function was observed in the Cryab / mice compared to wild-type. Interestingly, the levels of Cryab in plasma in wild-type mice increased significantly after the stroke, peaking at the 12 h time point. Elevated plasma levels were also detected in patients with ischemic stroke, particularly in the younger age group (ages 39–66). To test the hypothesis that increased plasma Cryab after stroke was a beneficial restorative response, wild type and Cryab / mice were given i.p. injections of recombinant Cryab protein starting 1 h before stroke onset and continuing at 12 h, 24 h, and daily afterward for 7 d in total, resulting in decreased lesion sizes. This therapeutic effect appears to be mediated by modulating the inflammatory response associated with stroke. In treated wild-type mice, a modest beneficial effect was also noted in animals starting the initial treatment 12 h after the stroke onset. If translated to the clinic, this benefit seen when providing the treatment 12 h after stroke would represent a significant improvement over tPA (Proc Natl Acad Sci 2011; 108:13287–13292).