Plasma fibronectin is neuroprotective following traumatic brain injury.
Promotion of repair and regeneration following traumatic brain injury remains a challenging clinical problem. While significant efforts have been made to reduce inhibitory extracellular matrix expression following central nervous system injury, much less attention has been given to the role of endogenous reparative matrix proteins, such as fibronectin. Traumatic brain injury leads to increased levels of plasma-derived fibronectin in the brain tissue, though the specific function of this protein following neurotrauma was unknown. In this study, we utilized conditional plasma fibronectin (pFN) knockout mice to examine the role of fibronectin following a traumatic insult. Injured mice deficient in pFN performed significantly worse on both motor and cognitive tasks, had significantly increased lesion volume and apoptotic cell death, and had significantly less phagocytic cells in the injured cortex compared to injured mice with normal pFN levels. Moreover, intravenous injections of fibronectin prior to the injury restored the neural deficits seen in the pFN deficient mice to that of wild type injured mice. These results demonstrate that fibronectin is neuroprotective to the traumatically injured brain and identify a novel target for therapeutic interventions.
Tate
Ciara C
CC
Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, 313 Ferst Dr., Atlanta, GA 30332, USA.
García
Andrés J
AJ
LaPlaca
Michelle C
MC
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000097:blood* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D002452:Cell Count; D016923:Cell Death; D005353:Fibronectins / Q000097:blood* / Q000172:deficiency / Q000494:pharmacology; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D018696:Neuroprotective Agents / Q000097:blood* / Q000494:pharmacology; D010586:Phagocytes / Q000473:pathology; D013550:Swimming
D005353:Fibronectins; D018696:Neuroprotective Agents