No 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 rapid increase in basic fibroblast growth factor (bFGF) production following spinal cord injury (SCI) in rats is thought to serve a role in the cellular processes responsible for the functional recovery often observed. In this study, bFGF was intrathecally administered continuously for 1 week beginning 30 min after a moderate (12.5 mm) spinal cord contusion in adult rats using the New York University impactor device. Osmotic minipumps were implanted into the lateral ventricle and lumbar thecal sac to deliver bFGF at a rate of 3 microg or 6 microg per day versus control vehicle. Animals were behaviorally tested for 6 weeks using the Basso, Beattie, Bresnahan locomotor rating scale and histologically assessed for both tissue sparing and glial reactivity rostral and caudal to the lesion. Rats treated with bFGF regained coordinated hindlimb movements earlier than controls and demonstrated consistent coordination from 4 to 6 weeks. Vehicle-treated rats showed only modest improvements in hindlimb function. The amount of spared tissue was significantly higher in bFGF-treated rats than in controls. Astrocyte and microglial reactivity was more pronounced in bFGF-treated animals versus controls. In summary, intrathecal infusion of exogenous bFGF following SCI significantly reduces tissue damage and enhances functional recovery. Early pharmacological intervention with bFGF following SCI may serve a neuroprotective role and/or create a proregenerative environment, possibly by modulating the neuroglial response.

Acute spinal cord injury in a rat model is well visualized on pre- and postcontrast MR scans at 1.5 T. Observation of T2 changes and disruption of the blood-spinal cord barrier provide markers for temporal assessment of spinal cord injury in the rat model.

Data from this study indicate possible compromise of neuronal, axonal, glial, and synaptic function after trauma, which may be a factor in motor deficits seen in animals after spinal cord contusion. The colocalization of the IgG stain with the HNE/protein stain is consistent with the hypothesis of a mutual cause-effect relationship between BSCB and oxidative stress in central nervous system trauma.