Systemic augmentation of alphaB-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation.

Abstract

Tissue plasminogen activator is the only treatment option for stroke victims; however, it has to be administered within 4.5 h after symptom onset, making its use very limited. This report describes a unique target for effective treatment of stroke, even 12 h after onset, by the administration of αB-crystallin (Cryab), an endogenous immunomodulatory neuroprotectant. In Cryab(-/-) mice, there was increased lesion size and diminished neurologic function after stroke compared with wild-type mice. Increased plasma Cryab was detected after experimental stroke in mice and after stroke in human patients. Administration of Cryab even 12 h after experimental stroke reduced both stroke volume and inflammatory cytokines associated with stroke pathology. Cryab is an endogenous anti-inflammatory and neuroprotectant molecule produced after stroke, whose beneficial properties can be augmented when administered therapeutically after stroke.

• Authors: Ahmet Arac, Sara E Brownell, Jonathan B Rothbard, Charlene Chen, Rose M Ko, Marta P Pereira, Gregory W Albers, Lawrence Steinman, Gary K Steinberg
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 108 Issue 32 Pg. 13287-92 (Aug 09 2011) ISSN: 1091-6490 [Electronic] United States
• PMID: 21828004 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Crystallin B Chain

Topics

• Animals
• Brain (drug effects, immunology, pathology)
• Humans
• Immune System (drug effects, immunology)
• Mice
• Stroke (blood, drug therapy, immunology, pathology)
• T-Lymphocytes (drug effects, immunology)
• Time Factors
• alpha-Crystallin B Chain (administration & dosage, blood, pharmacology, therapeutic use)