Outcome In Acute Spinal Cord Injury Research Articles

Neuroprotective Agents as an Adjuvant Treatment in Patients With Acute Spinal Cord Injuries: A Qualitative Systematic Review of Randomized Trials.

This was a systematic literature review. The objective of this study was to evaluate randomized clinical trials that address potential neuroprotective agents used to improve neurological outcome in patients with spinal cord injury (SCI). Clinical treatment of acute SCI has evolved significantly, but neurological recovery of severely injured patients remains modest. Neuroprotective agents may act to limit secondary damage in the sequence of pathophysiologic insults that occur after primary SCI. We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines of all clinical randomized trials that evaluated potential neuroprotective agents (drugs, stem cells, and any type of medicative interventions) in neurological outcome of acute SCI. All the studies were graded according to their level of evidence in accordance with the Oxford Level of Evidence-based Medicine. A total of 16 randomized clinical trials were included and fully analyzed in our review. The following 12 substances/drugs were analyzed: methylprednisolone (MP), naloxone, tirilizad, nimodipine, Sygen, autologous incubated macrophages, autologous bone marrow cells, minocycline, erythropoietin, ganglioside, vitamin D, and progesterone. Modest benefits were attributed to minocycline and Sygen (without statistical significance), and some benefits were obtained with erythropoietin and progesterone plus vitamin D in neurological outcome. For MP, the benefits are also controversial and may be attributed to statistical artifacts and with a high risk of adverse effects. The other substances did not change the final outcome. All studies were considered as grade B of recommendation (100%) and levels of evidences as B2 (81.25%) and B3 (18.75%). Our review reported some potential substances that may improve neurological outcome in acute SCI: MP, vitamin D associated with progesterone, and erythropoietin. Their potential benefits were modest in the evaluated studies, requiring further randomized clinical trials with large samples of patients, without statistical artifacts, for routine clinical use. Furthermore, potential adverse effects must be considered with the use of neuroprotective agents in SCI. Until then, the use of these substances may be experimental or restricted to specific clinical situations.

BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury

Transplantation of mesenchymal stem cells (MSCs) derived from bone marrow has been shown to improve functional outcome in spinal cord injury (SCI). We transplanted MSCs derived from human bone marrow (hMSCs) to study their potential therapeutic effect in SCI in the rat. In addition to hMSCs, we used gene-modified hMSCs to secrete brain-derived neurotrophic factor (BDNF-hMSCs). After a dorsal transection lesion was induced at T9, cells were microinjected on each side of the transection site. Fluorogold (FG) was injected into the epicenter of the lesion cavity to identify transected corticospinal tract (CST) neurons. At 5 weeks after transplantation, the animals were perfused. Locomotor recovery improvement was observed for the BDNF-hMSC group, but not in the hMSC group. Structurally there was increased sprouting of injured corticospinal tract and serotonergic projections after hMSC and BDNF-hMSC transplantation. Moreover, an increased number of serotonergic fibers was observed in spinal gray matter including the ventral horn at and below the level of the lesion, indicating increased innervation in the terminal regions of a descending projection important for locomotion. Stereological quantification was performed on the brains to determine neuronal density in primary motor (M1) cortex. The number of FG backfilled cells demonstrated an increased cell survival of CST neurons in M1 cortex in both the hMSC and BDNF-hMSC groups at 5 weeks, but the increase for the BDNF-hMSC group was greater. These results indicate that transplantation of hMSCs hypersecreting BDNF results in structural changes in brain and spinal cord, which are associated with improved functional outcome in acute SCI.