Beneficial effects of αB-crystallin in spinal cord contusion injury.
αB-crystallin is a member of the heat shock protein family that exerts cell protection under several stress-related conditions. Recent studies have revealed that αB-crystallin plays a beneficial role in a mouse model of multiple sclerosis, brain ischemia, and Alexander disease. Whether αB-crystallin plays a role in modulating the secondary damage after CNS trauma is not known. We report here that αB-crystallin mediates protective effects after spinal cord injury. The levels of αB-crystallin are reduced in spinal cord tissue following contusion lesion. In addition, administration of recombinant human αB-crystallin for the first week after contusion injury leads to sustained improvement in locomotor skills and amelioration of secondary tissue damage. We also provide evidence that recombinant human αB-crystallin modulates the inflammatory response in the injured spinal cord, leading to increased infiltration of granulocytes and reduced recruitment of inflammatory macrophages. Furthermore, the delivery of recombinant human αB-crystallin promotes greater locomotor recovery even when the treatment is initiated 6 h after spinal cord injury. Our findings suggest that administration of recombinant human αB-crystallin may be a good therapeutic approach for treating acute spinal cord injury, for which there is currently no effective treatment.
Departament de Biologia Cel.lular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain.
Armelle
A
Klopstein
Eva
E
Santos-Nogueira
Isaac
I
Francos-Quijorna
Adriana
A
Redensek
Samuel
S
David
Xavier
X
Navarro
Rubèn
R
López-Vales
D000818:Animals; D002464:Cell Migration Inhibition / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000627:therapeutic use; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology; D038203:alpha-Crystallin B Chain / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000627:therapeutic use*
D018836:Inflammation Mediators; D011994:Recombinant Proteins; D038203:alpha-Crystallin B Chain