Neurotrophic factors attenuate microvascular permeability disturbances and axonal injury following trauma to the rat spinal cord.
Alterations of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) and leakage of serum proteins induce vasogenic edema and cell damage. The possibility that two members of the neurotrophin family, BDNF or IGF-1 induce neuroprotection by attenuating the BSCB permeability following trauma was examined in a rat model. Repeated topical application of BDNF or IGF-1 (0.1 1microg, 0.5 microg or 1 microg in 10 microl) onto the spinal cord 30 min before SCI or 2, 5, 10 or 30 min thereafter significantly attenuated BSCB permeability to Evans blue and iodine. In the neurotrophin treated rats. edema formation, degradation of MBP, and myelin vesiculation were much less frequent compared to the untreated traumatised rats. The protective effect of BDNF and IGF-1 was most pronounced at the high dose (1 microg in 10 microl) given either 30 min before or within 10 min after SCI. The observations suggest that early intervention with neurotrophins in high doses following trauma (within 10 min) attenuates disturbances of the fluid microenvironment of the spinal cord. This indicates that BSCB opening plays an important role in SCI induced myelin vesiculation and cord pathology.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
D000818:Animals; D001369:Axons / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D020833:Diffuse Axonal Injury / Q000209:etiology* / Q000473:pathology; D004487:Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism; D013118:Spinal Cord Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor; D004676:Myelin Basic Protein; D007334:Insulin-Like Growth Factor I