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Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord injury.

Kim DH, Jahng TA - J. Korean Med. Sci. (2004)

Bottom Line: 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.Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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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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Figure 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).

Mentions: Unfortunately, some of the rats died of cystitis or other infections, so the number surviving ten weeks after SCI was five in the BDNF+MP group, five in the MP-only group, and four in control group. Observers blinded to the treatments performed all functional assessments and analyses, using the BBB open field locomotion scale. The MP-only group and control groups uniformly exhibited either paralysis or occasional uncoordinated hindlimb spasms. Three weeks after SCI, initial paralysis was attenuated in animals infused with MP+BDNF. Six weeks after injury, they demonstrated extensive joint movement in their hindlimbs, and their BBB score increased significantly relative to MP-only and control groups (Fig. 5, p<0.05). Rats in the MP-only group were not significantly different from the control group.


Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord injury.

Kim DH, Jahng TA - J. Korean Med. Sci. (2004)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822246&req=5

Figure 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).
Mentions: Unfortunately, some of the rats died of cystitis or other infections, so the number surviving ten weeks after SCI was five in the BDNF+MP group, five in the MP-only group, and four in control group. Observers blinded to the treatments performed all functional assessments and analyses, using the BBB open field locomotion scale. The MP-only group and control groups uniformly exhibited either paralysis or occasional uncoordinated hindlimb spasms. Three weeks after SCI, initial paralysis was attenuated in animals infused with MP+BDNF. Six weeks after injury, they demonstrated extensive joint movement in their hindlimbs, and their BBB score increased significantly relative to MP-only and control groups (Fig. 5, p<0.05). Rats in the MP-only group were not significantly different from the control group.

Bottom Line: 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.Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

Show MeSH
Related in: MedlinePlus