Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord.
It is likely that the environment within the injured spinal cord influences the capacity of fetal spinal cord transplants to support axonal growth. We have recently demonstrated that fetal spinal cord transplants and neurotrophin administration support axonal regeneration after spinal cord transection, and that the distance and amount of axonal growth is greater when these treatments are delayed by several weeks after injury. In this study, we sought to determine whether differences in inflammatory mediators exist between the acutely injured spinal cord and the spinal cord after a second injury and re-section, which could provide a more favorable environment for the axonal re-growth. The results of this study show a more rapid induction of transforming growth factor (TGF) beta1 mRNA expression in the re-injured spinal cord than the acutely injured spinal cord and an attenuation of proinflammatory cytokine mRNA expression. Furthermore, there was a rapid recruitment of activated microglia/macrophages in the degenerating white matter rostral and caudal to the injury but fewer within the lesion site itself. These findings suggest that the augmentation of TGFbeta-1 gene expression and the attenuation of pro-inflammatory cytokine gene expression combined with an altered distribution of activated microglia/macrophages in the re-injured spinal cord might create a more favorable milieu for transplants and axonal regrowth as compared to the acutely injured spinal cord.
Nakamura
Masaya
M
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20007, USA. bregmanb@georgetown.edu
Houghtling
Richard A
RA
MacArthur
Linda
L
Bayer
Barbara M
BM
Bregman
Barbara S
BS
D000818:Animals; D001369:Axons / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000502:physiology; D017628:Microglia / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D023282:Nuclease Protection Assays; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta