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Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury
Published on: February 23, 2015
Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord
1Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. spine@snuh.org
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.
Insights
Methylprednisolone (MP) is standard for spinal cord injury (SCI), but outcomes vary. Adding brain-derived neurotrophic factor (BDNF) after MP treatment improved functional recovery and axonal regeneration in rats with severe SCI.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Spinal Cord Injury Research
Background:
- Methylprednisolone (MP) is a standard acute treatment for spinal cord injury (SCI).
- MP's efficacy is variable, potentially due to suppressed neurotrophic factors.
- Brain-derived neurotrophic factor (BDNF) promotes neuronal growth and survival.
Purpose of the Study:
- To investigate if continuous brain-derived neurotrophic factor (BDNF) infusion enhances functional recovery after methylprednisolone (MP) treatment in severe spinal cord injury (SCI).
Main Methods:
- Adult rats with T10 contusion SCI received immediate intravenous MP.
- BDNF was administered intrathecally via osmotic mini-pump for six weeks.
- Immunohistochemistry (ED-1, GAP-43, NF, ChAT) and Basso-Beattie-Bresnahan (BBB) locomotor tests were used.
Main Results:
- BDNF did not affect MP's impact on inflammatory cell infiltration.
- MP with BDNF infusion showed increased axonal survival and regeneration (NF, GAP-43 expression) compared to MP alone.
- Adjunctive BDNF significantly improved locomotor function (BBB scores).
Conclusions:
- Continuous BDNF infusion following MP treatment improves functional recovery in severe SCI.
- BDNF enhances axonal regeneration without interfering with MP's acute anti-inflammatory effects.
- This combination therapy offers a promising strategy for SCI treatment.

