Efficacy of methylprednisolone therapy for the injured rat spinal cord

Abstract

Currently the synthetic glucocorticosteroid methylprednisolone sodium succinate (MPSS) is the standard therapy after acute spinal cord injury (SCI) in humans based on reported neurological improvements. The mechanisms for its beneficial actions are not entirely clear, but experimental evidence suggests MPSS affords some degree of neuroprotection. As many studies with rat models of SCI have been unable to demonstrate improved behavioral outcome or tissue sparing after MPSS treatment, we chose to stereologically assess whether it alters lesion volume and tissue sparing over time, as well as long-term behavioral recovery. Adult rats subjected to contusion SCI with the NYU impactor were administered either MPSS or saline for 24 hr beginning 5 min post injury. Over time the lesion dimensions were extremely dynamic, such that by 6 weeks post injury the volumes were reduced to a third of those seen after the first week. MPSS marginally reduced lesion volumes across time vs. controls, but the amount of spared gray and white matter remained unaltered between the two groups. Behavioral results further showed that MPSS failed to improve recovery of hind-limb function. These findings add to the emerging scrutiny of MPSS as the standard therapy for acute SCI, as well as indicate the existence of a therapeutic window for tissue sparing restricted to the first several days after this type of SCI in rats. Equally important, our results caution the use of lesion volume dimensions or percent tissue sparing at the epicenter as indicators of therapeutic efficacy because neither reflects the actual amount of tissue sparing.

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

“…This sparing of spinal cord tissue was largely resulted from the preservation of neuronal profiles and a reduction in apoptosis. This result is especially significant, as functional recovery has not previously been supported by changes in tissue sparing 22) . Caspases, which are both initiators and executioners in the apoptotic cascade, are directly integrated into the proteolytic activities that regulate apoptosis as well as cell survival 23,31) .…”

Calpain 1 Knockdown Improves Tissue Sparing and Functional Outcomes after Spinal Cord Injury in Rats

“…Although the BBB scale is an ordinal scale, differences between the treatments were compared using parametric statistical methods recommended by Scheff and colleagues. 24 …”

“…The spinal cord was removed and prepared for histological assessment as described previously. 19,24 Spinal cords were serially and transversely cryosectioned at a thickness of 20 lm. Every fifth section was mounted onto gelatin-coated slides and stored at -20°C.…”

Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury

“…10). Other species, e.g., rodents, have received less attention, but the results suggest a different outcome, with only a small window of opportunity for reducing tissue injury and with no improvement in motor outcome (11). Additional detrimental effects of glucocorticoids have been clearly documented, including potentiation of ischemic (12) and inflammatory (13) neuronal injury and potent suppression of neurotrophic factors, e.g., glial-derived neurotrophic factor (14).…”