Methylprednisolone and Interleukin-10 Reduce Gray Matter Damage in the Contused Fischer Rat Thoracic Spinal Cord but Do Not Improve Functional Outcome

Abstract

The effects of two antiinflammatory and neuroprotective agents, methylprednisolone (MP) and interleukin-10 (IL-10), singly and in combination on tissue damage, axonal preservation and functional recovery were studied in the contused adult Fischer rat thoracic spinal cord 12 weeks after injury. MP (30 mg/kg at 5 min, and 2 and 4 h after injury) was administered intravenously and IL-10 (15 or 30 microg/kg at 30 min after injury), intraperitoneally. MP, IL-10, or the combination significantly reduced the volume of damaged tissue (including cavities) compared to control animals. The loss of spinal tissue (cavities) was reduced after treatment with MP alone or combined with IL-10, but not with IL-10 alone. The reduction in tissue damage was confined to spinal gray matter; at the level of the lesion epicenter, the thickness of the lateral white matter columns was similar in all groups. Retrograde tracing using fast blue revealed that the number of spared propriospinal and supraspinal projections was similar in all groups at 12 weeks after the contusion. The open-field BBB-test showed no significant difference in hindlimb locomotion between groups. Our results demonstrate that all tested antiinflammatory treatments significantly increase the volume of spared spinal gray matter 3 months after a moderate contusion of the Fischer rat thoracic spinal cord, but none of the treatments improved axonal preservation or functional recovery.

The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery

“…First, the dose of rolipram most effective as an antiinflammatory agent is 3-to 6-fold higher than the optimal dose we report here for functional recovery after spinal cord injury (22)(23)(24). Second, methylprednisolone, a known antiinflammatory already used as a therapy in humans, prevents some secondary cell loss in animal models of spinal cord injury but does not produce any significant improvement in functional recovery (25)(26)(27) Regardless, of the mechanism of action, rolipram is effective and should be considered as a therapy for spinal cord injury. It is of note that rolipram is effective at lower but not at high doses, for both the culture and the in vivo assays.…”

Bone Marrow Stromal Cell-Mediated Tissue Sparing Enhances Functional Repair after Spinal Cord Contusion in Adult Rats

“…Within the analyzed segStudent t-test and, in case of multiple time points, ment, tissue was considered spared if it lacked cavities, repeated measures ANOVA followed by Tukey's post areas with densely packed small cells resembling infilhoc test were used to determine statistical differences trated neutrophils and lymphocytes, and neurons with between groups. Differences were accepted as statistidarkly stained cytoplasmic Nissl bodies (46,62,63 (20) and used to determine the blood vessel density (RECA-1-positive blood vessels per tissue surface Spared tissue volume in a 3.4-mm-long segment centered at the contusion (Fig. 1A) was determined in area) using Stereo Investigator (MicroBrightField Inc.) BMSC TRANSPLANTS IMPROVE FUNCTION AFTER SCI 1565 spared in BMSC-transplanted rats consisted mostly of white matter (97.03 ± 2.6%) and little of gray matter (2.97 ± 2.6%) (Fig.…”

Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells

“…The volume of the cavity was then calculated by multiplying the average area by depth of the spinal cord as previously reported. 39 The other sections were stained with luxol fast blue for myelin. This experiment was reviewed and approved by the Institutional Animal Care and Use Committee of the Catholic University of Korea and was conducted according to that committee's guidelines.…”