Long-term effects of methylprednisolone following transection of adult rat spinal cord.

Abstract

Clinically, high-dose treatment with the glucocorticosteroid, methylprednisolone (MP), within 8 h after spinal cord injury, has been shown to improve neurological recovery. The current standard of care is to administer MP as a bolus of 30 mg/kg followed by a 23-h infusion of 5.4 mg/kg/h to spinal cord injured patients. To better understand the role of MP in neuroprotection, we have studied how MP administration affects macrophage accumulation, tissue loss, and axonal dieback at 1, 2, 4 and 8 weeks after a complete transection of the eighth thoracic spinal cord in the adult rat. A 30 mg/kg dose of MP was administered intravenously at 5 min, and 2 and 4 h after injury. The number of ED1 (antibody against microglia/macrophages) -positive cells was quantified in a 500-micrometer-wide strip of tissue directly adjacent and parallel to the transection. At all time points, MP treatment led to a significant decrease in the number of ED1-positive cells in both rostral and caudal stumps. Over the 2-month post-transection period, the average MP-induced reduction in the number of ED1-positive cells was 82% in the rostral cord stump and 66% in the caudal stump. Using a computerized image analysis system, it was observed that MP treatment resulted in a significant reduction in tissue loss in both cord stumps at 2, 4 and 8 week post-injury. Over the 2-month post-lesion period, the average MP-induced reduction in tissue loss in the caudal cord stump was higher than that in the rostral stump; 48 versus 37%, respectively. Immunostaining for neurofilaments and growth-associated protein-43 (GAP-43) revealed the presence of numerous axons near and in the lesion site. Anterograde neuronal tracing with biotinylated dextran amine showed that, in MP-treated animals, dieback of vestibulospinal fibres, but not of corticospinal fibres, was significantly diminished at all time points studied. In addition, with MP administration, 1 and 2 weeks after injury, an increase in the number of vestibulospinal fibres was found at 1 and 2 mm from the transection, suggesting transient regenerative sprouting of these fibres. The results demonstrate that treatment with MP shortly after spinal cord transection in the adult rat led to a long-term reduction of ED1-positive cells and spinal tissue loss, reduced dieback of vestibulospinal fibres, and a transient sprouting of vestibulospinal fibres near the lesion at 1 and 2 weeks post-lesion. The possible relationships between the inflammatory changes, spinal tissue sparing, and axonal survival and sprouting are complex and need to be further explored.

• Authors: M Oudega, C G Vargas, A B Weber, N Kleitman, M B Bunge
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 11 Issue 7 Pg. 2453-64 (Jul 1999) ISSN: 0953-816X [Print] France
• PMID: 10383635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neuroprotective Agents
• Methylprednisolone

Topics

• Animals
• Cell Count (drug effects)
• Female
• Macrophages (pathology)
• Methylprednisolone (pharmacology)
• Monocytes (pathology)
• Nerve Fibers (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Pyramidal Tracts (drug effects, physiopathology)
• Rats
• Rats, Inbred F344
• Spinal Cord (drug effects, pathology, physiopathology)
• Spinal Cord Injuries (pathology, physiopathology)
• Time Factors
• Vestibular Nuclei (drug effects, physiopathology)
• Wounds, Penetrating (pathology, physiopathology)