Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord

• Published in: Experimental neurology Vol. 184; no. 1; pp. 313 - 325
• Main Authors: Nakamura, Masaya, Houghtling, Richard A, MacArthur, Linda, Bayer, Barbara M, Bregman, Barbara S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2003; Elsevier
• Subjects: Animals; Axons - physiology; Biological and medical sciences; Cytokine; Cytokines - biosynthesis; Female; Gene Expression Regulation - physiology; Immunohistochemistry; Inflammatory response; Macrophage; Macrophages - physiology; Medical sciences; Microglia; Microglia - physiology; Nerve Degeneration - pathology; Nerve Regeneration - physiology; Neurology; Nuclease Protection Assays; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal cord injury; TGFβ; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - genetics; TGFβ; Inflammatory response; Spinal cord injury; Cytokine; Microglia; Macrophage; Neurotrophin; Spinal cord; Rat; Growth; Neuroglia; Central nervous system; Recruitment; Attenuation; Nervous system diseases; Rodentia; Gene expression; Section; White matter; Regeneration; Vertebrata; Mammalia; Treatment; Animal; Distribution; Environment; Transforming growth factor β1; Lesion
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/S0014-4886(03)00361-3

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 (Coumans et al., 2001). 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) β1 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 TGFβ-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.