J Korean Med Sci.  2004 Feb;19(1):113-122. 10.3346/jkms.2004.19.1.113.

Continuous Brain-derived Neurotrophic Factor (BDNF) Infusion After Methylprednisolone Treatment in Severe Spinal Cord Injury

• Kim DH
• Jahng TA

• KMID: 1785704
• DOI: http://doi.org/10.3346/jkms.2004.19.1.113

Abstract

Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral level of the spinal cord in adult rats. The rats received MP intravenously immediately after the injury and BDNF was infused intrathecally using an osmotic mini-pump for six weeks. Immunohistochemical methods were used to detect ED-1, Growth associated protein-43 (GAP-43), neurofilament (NF), and choline acethyl transferase (ChAT) levels. BDNF did not alter the effect of MP on hematogenous inflammatory cellular infiltration. MP treatment with BDNF infusion resulted in greater axonal survival and regeneration compared to MP treatment alone, as indicated by increases in NF and GAP-43 gene expression. Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test. This study demonstrated that continuous infusion of BDNF after initial MP treatment improved functional recovery after severe spinal cord injury without dampening the acute effect of MP.

Keyword

Regeneration; Brain-Derived Neurotrophic Factor; Methylprednisolone; Spinal Cord Injuries

MeSH Terms

Animals
Anti-Inflammatory Agents/pharmacology
Axons/pathology
Brain-Derived Neurotrophic Factor/metabolism/*pharmacology
Choline O-Acetyltransferase/metabolism
Female
GAP-43 Protein/metabolism
Gene Expression Regulation
Immunohistochemistry
Methylprednisolone/metabolism/*pharmacology
Osmosis
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord/pathology
Spinal Cord Injuries/*pathology
Time Factors

Figure

• 

  Fig. 1 Immunohistochemical staining for ED-1 at the contusion injury site (×40). 3 days after the SCI, many ED-1-positive inflammatory cells (stained with brown color) are observed at the contusion site in the untreated spinal cord (A). In contrast, ED-1-positive inflammatory cells are markedly decreased in the MP-only (B) and MP+BDNF (C) infused animals. This difference, represented as means±S.D. in (D), is significant (p<0.05).

• 

  Fig. 2 Immunohistochemical staining for NF at the contusion injury site (×40). Ten weeks after SCI, fewer NF-positive neuronal fibers are observed at the lesion in the control (A) and MP-only groups (B). More NF-positive neuronal axons survive in the spinal cords of rats in the MP+BDNF group (C). This difference, represented as means±S.D. in (D), is significant (p<0.05).

• 

  Fig. 3 Immunohistochemical staining for GAP-43 at the contusion injury site (×40). Ten weeks after SCI, many GAP-43-positive neurites are found in the MP+BDNF group (C), while few are detected in the control (A) and MP-only treated (B) rats. This difference, represented as means±S.D. in (D), is significant (p<0.05).

• 

  Fig. 4 Immunohistochemical staining for ChAT at the contusion injury site (×40). More ChAT-positive axons appear in MP+BDNF rats (C) ten weeks after SCI than in the other two groups (A, B). This difference, represented as means±S.D. in (D), is significant (p<0.05).

• 

  Fig. 5 BBB (Basso Beattie Bresnahan) locomotor score (means±S.D.). Rats that received MP+BDNF revealed active coordinated hindlimb movement, six weeks after SCI. The MP-only and untreated rats exhibited either paralysis or occasional uncoordinated hindlimb spasms ten weeks after SCI. Differences each week were determined by post hoc means-corrected t-tests (p<0.05).

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