Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation.

STUDY DESIGN: Experimental study with rats. OBJECTIVE: To evaluate functional and histological effects of tacrolimus (FK 506) and erythropoietin (EPO) after experimental spinal cord contusion injury (SCI). SETTING: Brazil. METHODS: Wistar rats (n=60) were submitted to SCI with the NYU Impactor system. The control group received saline; the EPO group received EPO; the group EPO+FK 506 received EPO associated with tacrolimus and the group FK 506 received tacrolimus only. The Sham group underwent SCI, but did not receive any drug. Locomotor function was evaluated after SCI by BBB (Basso, Beattie and Bresnahan) weekly and by the motor-evoked potential test in 42 days. The spinal cord was histologically evaluated. RESULTS: There was a significant difference between treated and the control groups from the seventh day on for BBB scores, with no difference between the groups EPO and EPO+FK 506 by the end of the study. There were significant differences between groups for necrosis and bleeding, but not for hiperemia, degeneration and cellular infiltrate. Axon neuron count was different between all groups (P=0.001), between EPO+FK 506 and FK 506 (P=0.011) and between EPO+FK 506 and Sham (P=0.002). Amplitude was significantly different between all groups except between control and sham. For latency, there was no difference. CONCLUSIONS: This study did not reveal significant differences in the recovery of locomotor function, or in the histological and electrophysiological analysis in animals treated with EPO and tacrolimus after thoracic SCI.

Gunshot injuries in the spine.

STUDY DESIGN: Review article. OBJECTIVES: To review the literature regarding treatment approaches in cases of gunshot wounds (GSWs) affecting the spine. SETTING: Brazil. METHODS: Narrative review of medical literature. RESULTS: GSWs are an increasing cause of morbidity and mortality. Most patients with spinal GSW have complete neurological deficit. The injury is more common in young men and is frequently immobilizing. The initial approach should follow advanced trauma life support, and broad-spectrum antibiotic therapy should be initiated immediately, especially in patients with perforation of the gastrointestinal tract. The indications for surgery in spinal GSW are deterioration of the neurologic condition in a patient with incomplete neurological deficit, the presence of liquor fistula, spinal instability, intoxication by the metal from the bullet or risk of bullet migration. CONCLUSION: Surgical treatment is associated with a higher complication rate than conservative treatment. Therefore, the surgeon must know the treatment limitations and recognize patients who would truly benefit from surgery.

Effects of antidepressant and treadmill gait training on recovery from spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the influences of antidepressant treatment, treadmill gait training and a combination of these therapies in rats with experimental, acute spinal cord injury (SCI). SETTING: Brazil. METHODS: 48 Wistar rats were given standardized SCI; rats were then randomly assigned to four treatment groups: (1) motor rehabilitation therapy for 1 hour daily (gait training); (2) daily treatment with the antidepressant, fluoxetine (0.3 ml per 100 g intraperitoneally), beginning 24 h after the trauma; (3) combined fluoxetine treatment and gait training, or (4) untreated (controls). Neurological recovery was tested with the Basso, Beattie and Bresnahan (BBB) scale at 2, 7, 14, 21, 28 ,35 and 42 days after injury. Moreover, on day 42, all rats underwent a motor-evoked potential test (MEP); then, after euthanasia, histopathological evaluation was conducted in the area of SCI. RESULTS: Based on the BBB scale, the combined treatment group showed significantly greater improvement compared with the other three groups, from the 14th to the 42nd day of observation. The MEP revealed that all treated groups showed significant improvement compared with the control group (P<0.02 for latency and P<0.01 for amplitude). CONCLUSION: Our results indicated that a combination of antidepressant and treadmill gait training was superior to either treatment alone for improving functional deficits in rats with experimental, acute SCI.

Evaluation of the effects of hyperbaric oxygen therapy for spinal cord lesion in correlation with the moment of intervention.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the functional effect of hyperbaric oxygen therapy administered shortly, one day after, and no intervention (control) in standardized experimental spinal cord lesions in Wistar rats. SETTING: São Paulo, Brazil. METHODS: In all, 30 Wistar rats with spinal cord lesions were divided into three groups: one group was submitted to hyperbaric oxygen therapy beginning half an hour after the lesion and with a total of 10 one-hour sessions, one session per day, at 2 atm; the second received the same treatment, but beginning on the day after the lesion; and the third received no treatment (control). The Basso, Beattie and Bresnahan scales were used for functional evaluation on the second day after the lesion and then weekly, until being killed 1 month later. RESULTS: There were no significant differences between the groups in the functional analysis on the second day after the lesion. There was no functional difference comparing Groups 1 and 2 (treated shortly after or one day after) in any evaluation moment. On the 7th day, as well as on the 21st and 28th postoperative days, the evaluation showed that groups 1 and 2 performed significantly better than the control group (receiving no therapy). CONCLUSION: Hyperbaric chamber therapy is beneficial in the functional recovery of spinal cord lesions in rats, if it is first administered just after spinal cord injury or within 24 h.

Potentializing the effects of GM1 by hyperbaric oxygen therapy in acute experimental spinal cord lesion in rats.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the effect of GM1 ganglioside, hyperbaric oxygen and both in combination, in the treatment of experimental spinal cord lesions in rats. SETTING: Brazil. METHODS: Thirty-two Wistar rats with spinal cord lesions were divided into four groups: one group received GM1 ganglioside, one was submitted to hyperbaric oxygen therapy (HBOT), the third received both treatments and the fourth received no treatment (control). RESULTS: There were no significant differences between the groups in the histological analysis, for any of the variables (necrosis, hemorrhage, hyperemia, cystic degeneration, P>0.06). Neither were there any significant differences in the comparison of left and right sides in the functional tests (P>0.06 for all). No significant differences were found in the locomotor ratings, in the comparison of groups at 2, 7, 21 and 28 days after the surgical procedure. However, in the evaluation on day 14, group 3, which received the combined therapy, showed a significantly higher Basso Beattie and Bresnahan score than the other groups (P=0.015). CONCLUSION: The therapeutic effect of GM1 in locomotor evaluation of rats submitted to spinal cord lesion is anticipated by HBOT.

Stem cells in the treatment of chronic spinal cord injury: evaluation of somatosensitive evoked potentials in 39 patients.

STUDY DESIGN: A prospective, non-randomized clinical series trial. OBJECTIVE: To evaluate the effect of autogenous undifferentiated stem cell infusion for the treatment of patients with chronic spinal cord injury (SCI) on somatosensory evoked potentials (SSEPs). SETTING: A public tertiary hospital in São Paulo, Brazil. METHODS: Thirty-nine consecutive patients with diagnosed complete cervical and thoracic SCI for at least 2 years and with no cortical response in the SSEP study of the lower limbs were included in the trial. The trial patients underwent peripheral blood stem cell mobilization and collection. The stem cell concentrate was cryopreserved and reinfused through arteriography into the donor patient. The patients were followed up for 2.5 years and submitted to SSEP studies to evaluate the improvement in SSEPs after undifferentiated cell infusion. RESULTS: Twenty-six (66.7%) patients showed recovery of somatosensory evoked response to peripheral stimuli after 2.5 years of follow-up. CONCLUSION: The 2.5-year trial protocol proved to be safe and improved SSEPs in patients with complete SCI. SPONSORSHIP: None.

DNA polymorphisms as tools for spinal cord injury research.

STUDY DESIGN: Data mining of single nucleotide polymorphisms (SNPs) in gene pathways related to spinal cord injury (SCI). OBJECTIVES: To identify gene polymorphisms putatively implicated with neuronal damage evolution pathways, potentially useful to SCI study. SETTING: Departments of Psychiatry and Orthopedics, Faculdade de Medicina, Universidade de São Paulo, Brazil. METHODS: Genes involved with processes related to SCI, such as apoptosis, inflammatory response, axonogenesis, peripheral nervous system development and axon ensheathment, were determined by evaluating the 'Biological Process' annotation of Gene Ontology (GO). Each gene of these pathways was mapped using MapViewer, and gene coordinates were used to identify their polymorphisms in the SNP database. As a proof of concept, the frequency of subset of SNPs, located in four genes (ALOX12, APOE, BDNF and NINJ1) was evaluated in the DNA of a group of 28 SCI patients and 38 individuals with no SC lesions. RESULTS: We could identify a total of 95,276 SNPs in a set of 588 genes associated with the selected GO terms, including 3912 nucleotide alterations located in coding regions of genes. The five non-synonymous SNPs genotyped in our small group of patients, showed a significant frequency, reinforcing their potential use for the investigation of SCI evolution. CONCLUSION: Despite the importance of SNPs in many aspects of gene expression and protein activity, these gene alterations have not been explored in SCI research. Here we describe a set of potentially useful SNPs, some of which could underlie the genetic mechanisms involved in the post trauma spinal cord damage.

Antioxidative therapy in contusion spinal cord injury.

INTRODUCTION: Some studies have made use of the antioxidative capabilities of high doses of vitamins C and E with the aim of neutralizing the noxious effects of free radicals following spinal cord lesion. OBJECTIVES: To evaluate the effects of vitamins C and E, separately and together, on the functional performance of rats that were subjected to standardized spinal cord contusion. MATERIALS AND METHODS: Forty male Wistar rats were used, divided into four groups of 10 animals each. Group 3 received vitamin C 100 mg kg(-1) day(-1) intraperitoneally; Group 2 received vitamin E 100 mg kg(-1) day(-1) orally; Group 1 received vitamins C and E, at the same dosages; and Group 4 was the control. The vitamin therapy was administered for 1 month and then the animals were killed. A direct contusional injury was caused and functional evaluation was performed using the Basso, Beattie and Bresnahan rating scale. The rats were evaluated on the second postoperative day and weekly thereafter, until the end of the experiment. RESULTS: The results were evaluated by means of the one-tailed, non-paired and non-parametric Mann-Whitney test, comparing the groups two by two. No significant difference in functional performance was observed between the groups. CONCLUSION: The use of vitamins C and E in these rats did not improve their neurological performance. However, histopathological examination showed that the inflammatory response was less intense following administration of the combination of vitamins C and E.

WITHDRAWN: Association between polymorphisms in genes of inflammatory response and axonal repair with spinal cord injury.

Ahead of Print article withdrawn by publisher. Please see re-submitted article 'DNA polymorphisms as tools for spinal cord injury research' Spinal Cord advance online publication, 20 May 2008; doi:10.1038/sc.2008.67.