4.7 Article

Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony-Stimulating Factor in Rats with Spinal Cord Injury

Journal

CNS NEUROSCIENCE & THERAPEUTICS
Volume 21, Issue 9, Pages 698-707

Publisher

WILEY-BLACKWELL
DOI: 10.1111/cns.12429

Keywords

G-CSF; Intrathecal; Methylprednisolone; Spinal cord injury; Transforming growth factor

Funding

  1. Ministry of Science and Technology, Taiwan [99-2628-B-182A-003-MY2, 101-2314-B-182A-023-MY2]
  2. Chang Gung Memorial Hospital [CMRPG8A0151-3]
  3. National Research Program for Biopharmaceuticals, Taiwan [103-2325-B-110-001]

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AimsTo date, no reliable methods have proven effective for treating spinal cord injury (SCI). Even systemic administration of methylprednisolone (MP) remains controversial. We previously reported that intrathecal (i.t.) administration of granulocyte colony-stimulating factor (G-CSF) improves outcome after experimental spinal cord ischemic insults in rats. The present study aimed to examine the neuroprotective efficacy of i.t. G-CSF or MP in rats with SCI. MethodsFemale rats were subjected to spinal cord contusion injury at T10 using NYU impactor. We i.t. administered G-CSF (10g) or MP (one bolus of 100g, followed by 18g/h infusion for 23h) immediately after SCI. ResultsBoth G-CSF and MP significantly improved the rats' motor function after SCI. Immunofluorescence staining revealed suppressed expression of transforming growth factor-beta 1 (TGF-1), chondroitin sulfate proteoglycans (neurocan and phosphacan), OX-42 and tumor necrosis factor alpha after i.t. G-CSF, but not MP, in rats with SCI. In addition, G-CSF significantly decreased the expression of astrocytic TGF-1 and glial fibrillary acidic protein around the injury site. Furthermore, rats with G-CSF treatment showed increased neurofilament expression beyond the glial scars. ConclusionDirect i.t. administration of G-CSF provides a promising therapeutic option for SCI or related spinal diseases.

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