Drug Stability ; Methylprednisolone Hemisuccinate ; administration & dosage

Recent clinical trials have reported that methylprednisolone sodium succinate administered within 8 hours improves neurological recovery in human spinal cord injury (SCI). Methylprednisolone, however, was ineffective and possibly even deleterious when given more than 8 hours after injury. This finding suggests that a therapeutic time window exists in spinal cord injury. In order to determine the doses, durations and timing of methylprednisolone treatment for optimal neuroprotection, a single or two bolus dose of methylprednisolone (30 mg/kg) was administered at 10, 30, 120, 150 and 240 min. after three graded spinal cord injury. The primary outcome measure was 24-hour spinal cord lesion volumes estimated from spinal cord Na+ and K+ shifts. A single 30 mg/kg dose of methylprednisolone at 10 min. after injury significantly reduced 24-hour lesion volumes in injured rat spinal cords. However, any other methylprednisolone treatment starting 30 min. or more after injury had no effect on 24-hour lesion volumes compared to the vehicle control group. Moreover, delayed treatment increased lesion volumes in some cases. These results suggest that the NYU SCI model has a very short therapeutic window.
Animal ; Drug Administration Schedule ; Male ; Methylprednisolone Hemisuccinate/therapeutic use ; Methylprednisolone Hemisuccinate/administration & dosage* ; Neuroprotective Agents/therapeutic use ; Neuroprotective Agents/administration & dosage* ; Rats ; Rats, Long-Evans ; Spinal Cord/pathology ; Spinal Cord Injuries/pathology ; Spinal Cord Injuries/drug therapy*

OBJECTIVETo investigate the effects and apoptosis of intrathecal injection of Methylprednisolone Sodium Succinate (MPss) for acute spinal cord injury (SCI) in New Zealand rabbits.

METHODSSeventy-two healthy New Zealand rabbits were used for the procedure and were randomly divided into two groups: SCI group and SHAM group, which was both divided into 6 subgroups, such as the vehicle group, the MPss intrathecal injection groups (1.5 mg/kg, 3.0 mg/kg, 6.0 mg/kg group), the MPss intravenous injection group and the combined injection group. TARLOV score was tested daily to evaluate the motor function. The rabbits were sacrificed 7 days after the surgery and the thoracic spinal cord sections and the sacral sections where MPss was injected were harvested for HE and TUNEL staining. Two-Factors Repeated Measures analysis of variance for TARLOV scores tested at various times and One-Way ANOVA analysis of variance for data between groups were used.

RESULTSeven days after surgery in SCI group, there was no statistical difference between the TARLOV scores of intrathecal injection of MPss 3.0 mg/kg group, 6.0 mg/kg group and MPss intravenous injection group (P > 0.05), which were all better than the vehicle group (F = 4.762, P < 0.05). Referring to the lymphocyte infiltration at the injury site in SCI group, there was statistical difference between MPss intrathecal injection 6.0 mg/kg group (1.33 ± 0.21) and the vehicle group (2.67 ± 0.21) (F = 5.793, P < 0.05) and no statistical difference between intrathecal injection of MPss 6.0 mg/kg group and MPss intravenous injection group (P > 0.05). As for the lymphocyte infiltration at the intrathecal injection site in SHAM group, there was statistical difference between MPss intrathecal injection 6.0 mg/kg group (2.50 ± 0.55) and the vehicle group (0.50 ± 0.55) (F = 17.333, P < 0.05). TUNEL staining in SCI group showed statistical difference between MPss intrathecal injection 6.0 mg/kg group (6.3 ± 1.5) and the vehicle group (20.3 ± 2.2) (F = 71.279, P < 0.05).

CONCLUSIONSIntrathecal injection of MPss can improve the functional recovery of lower limb and decrease apoptosis of neuron cells,which can provide same effects as the traditional intravenous injection of MPss in New Zealand rabbits.

Acute Disease ; Analysis of Variance ; Animals ; Disease Models, Animal ; Injections, Spinal ; Male ; Methylprednisolone Hemisuccinate ; administration & dosage ; therapeutic use ; Rabbits ; Recovery of Function ; Spinal Cord Injuries ; drug therapy

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Lymphoma, T-Cell ; drug therapy ; pathology ; Male ; Methylprednisolone Hemisuccinate ; administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local ; drug therapy ; Remission Induction