Acute Spinal Cord Injury In Rats Research Articles

The cross-talk between autophagy and endoplasmic reticulum stress in blood-spinal cord barrier disruption after spinal cord injury.

Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in acute spinal cord injury.

Nanoparticle Technologies in the Spinal Cord

Nanoparticles are increasingly being studied within experimental models of spinal cord injury (SCI). They are used to image cells and tissue, move cells to specific regions of the spinal cord, and deliver therapeutic agents locally. The focus of this article is to provide a brief overview of the different types of nanoparticles being studied for spinal cord applications and present data showing the capability of nanoparticles to deliver the chondroitinase ABC (chABC) enzyme locally following acute SCI in rats. Nanoparticles releasing chABC helped promote axonal regeneration following injury, and the nanoparticles also protected the enzyme from rapid degradation. In summary, nanoparticles are viable materials for diagnostic or therapeutic applications within experimental models of SCI and have potential for future clinical use.

NEUROPROTECTIVE EFFECTS OF MANGIFERIN ON ACUTE SPINAL CORD INJURY IN RATS AND ITS MECHANISM

To investigate the protective effect of mangiferin on acute spinal cord injury (SCI) in rats and its mechanism. Ninety Sprague Dawley rats were randomly divided into 5 groups, 18 rats in each group. SCI was induced by using the Allen's method (60 g/cm) at T9 level in the rats of groups B, C, D, and E; laminectomy was performed at T8-10 in group A. The rats were injected intraperitoneally with saline in groups A and B, and with mangiferin in groups C (10 mg/kg), D (25 mg/kg), and E (50 mg/kg) every day for 30 days. The survival condition of rats was observed after operation; at 24, 48, and 72 hours after operation, the motor function of the hind limb was evaluated by the Basso, Beattie, Bresnahan (BBB) scores. The spinal cord edema was assessed by measuring the water content in spinal cord tissues at 72 hours. Meanwhile, malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were detected by ELISA; nuclear factor κB (NF-κB), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 were measured via ELISA at the same time. Caspase-3 and Caspase-9 were also detected by ELISA after mangiferin treatment for 30 days. The expressions of Bax and Bcl-2 proteins were detected by Western blot. Pathological changes of the spinal cord was observed by HE staining. And Caspase-3 protein expression was detected by immunohistochemical staining. All rats survived to the end of experiment. BBB scores of groups B, C, D, and E were significantly less than that of group A (P<0.05), and it showed an increase trend from groups B to E (P<0.05). The content of water of groups B, C, D, and E were significantly greater than that of group A (P<0.05), and it showed a decrease trend from groups B to E (P<0.05). ELISA showed that the activities of MDA, NF-κB, TNF-α, IL-1β, IL-6, Caspase-3, and Caspase-9 in groups B, C, D, and E were significantly greater than that in group A (P<0.05), and they showed decrease trends from groups B to E (P<0.05). Meanwhile, the activities of CAT, SOD, and GSH in groups B, C, D, and E were significantly less than that in group A (P<0.05), and they showed increase trends from groups B to E (P<0.05). Western blot showed that the relative expression of Bax protein in groups B, C, D, and E were significantly greater than that in group A (P<0.05), and it showed a decrease trend from groups B to E (P<0.05). Meanwhile, the relative expression of Bcl-2 protein in groups B, C, D, and E were significantly less than that in group A (P<0.05), and it showed an increase trend from groups B to E (P<0.05). Histological observation showed that the pathological changes in group B were accord with that in SCI, and the degree of necrosis in groups C, D, and E were significantly improved when compared with that in group B, and the effect was better in group E than group D, and group D than group C. Immunohistochemical staining showed that the absorbance (A) value of Caspase-3 in groups B, C, D, and E were significantly greater than that in group A (P<0.05), and it showed a decrease trend from groups B to E (P<0.05). Mangiferin has neuroprotective effects on acute SCI in rats by alleviating edema of spinal cord, inhibiting oxidative stress and inflammation response, and regulating the Bcl-2 and Bax pathway.

MicroRNA-9 controls apoptosis of neurons by targeting monocyte chemotactic protein-induced protein 1 expression in rat acute spinal cord injury model.

For the purpose of an early identification of intervention targets for acute spinal cord injury (ASCI), we investigated the changes in expression levels of microRNA-9 (miR-9) and MCPIP1 in rat ASCI model. A total of 108 healthy rats were randomly divided into non-ASCI group (n=18) and five ASCI groups, 6h, 12h, 24h, 3 days and 7 days, representing the experimental time points following ASCI (n=18 per group). Hematoxylin and eosin (HE) staining was used to assess the ASCI damage, and quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH) were employed for the detection of miR-9 and MCPIP1 mRNA expression. HE staining results showed normal neuronal morphology in the non-ASCI group, but spinal cord tissue at 6h after ASCI showed developing neuronal necrosis. Acute inflammatory response was evident at 12h and 24h, with immune cells infiltrating into the gray matter. Vascular permeability increased and the nerve cells in gray-white matter exhibited extensive damage and necrosis at 24h and 7 days after ASCI. MiR-9 expression in ASCI tissue was significantly lower than that in normal spinal cord tissue. Statistical analysis showed a significant decrease in miR-9 expression in all the ASCI groups, compared to the non-ASCI group. Results from real-time PCR analysis revealed that MCPIP1 expression in all the ASCI groups was significantly higher than the non-ASCI group, and MCPIP1 expressions gradually increased with times at 6h-24h after ASCI. ISH revealed the following results after ASCI (1) miR-9 and MCPIP1 mRNA expression mainly distributed in ventral horn motor neurons, (2) miR-9 expression was high at 7 day after ASCI and (3) in the non-ASCI group, MCPIP1 expression was high at 6h, 12h, 24h and 3 days. MCPIP1 is significantly up-regulated after ASCI. The negative relationship between MCPIP1 and miR-9 suggest that MCPIP1 mRNA could be a target of miR-9 during ASCI. Thus, miR-9 is a marker for apoptosis in neurons, and an excellent therapeutic target for ASCI patients.

The Neuroprotective Effect of Puerarin in Acute Spinal Cord Injury Rats

Background: Acute spinal cord injury (SCI) leads to permanent disabilities. This study evaluated the neuroprotective effect of puerarin, a natural extract, in a rat model of SCI. Methods: Acute SCI models were established in rats using a modified Allen's method. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by H&E staining. Neuron survival and glial cells activation were evaluated by immunostaining. ELISA and realtime PCR were used to measure secretion and gene expression of cytokines. TUNEL staining was used to examine cell apoptosis and western blot analysis was used to detect protein expression. Results: Puerarin significantly increased BBB score in SCI rats, attenuated histological injury of spinal cord, decreased neuron loss, inhibited glial cells activation, alleviated inflammation, and inhibited cell apoptosis in the injured spinal cords. In addition, the downregulated PI3K and phospho-Akt protein expression were restored by puerarin. Conclusion: Puerarin accelerated locomotor function recovery and tissue repair of SCI rats, which is associated with its neuroprotection, glial cell activation suppression, anti-inflammatory and anti-apoptosis effects. These effects may be associated with the activation of PI3K/Akt signaling pathway.

Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats.

Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor-κB ligand (receptor activator of nuclear factor-κB ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI-induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol-treated rats. These results indicate that carvedilol exhibits anti-inflammatory and anti-oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats.

Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway

Curcumin, a yellow pigment extracted from Carcuma longa, has been demonstrated to have extensive pharmacological activity in various studies, and it exhibits protective effects on injuries involving a number of human organs. The present study was designed to evaluate the potential effect and underlying mechanism of curcumin on the motor function and spinal cord edema in a rat acute spinal cord injury (SCI) model. The SCI model was induced by a heavy object falling. At 30min after the SCI was successfully induced, the animals were intraperitoneally given 40mg/kg curcumin. The Basso, Beattie and Bresnahan scores showed that curcumin moderately improved the recovery of the motor function in the injured rats, and hematoxylin–eosin staining demonstrated the role of this compound in reducing the hemorrhage, edema and neutrophil infiltration of the traumatic spinal cord. Furthermore, curcumin also inhibited the SCI-associated aquaporin – 4 (AQP4) overexpression and glial fibrillary acidic protein (GFAP) and repressed the unusual activation of the JAK/STAT signaling pathway. In conclusion, our data demonstrate that curcumin exhibits a moderately protective effect on spinal cord injury, and this effect might be related to the inhibition of overexpressed AQP4 and GFAP and the activated JAK/STAT signaling pathway. Curcumin may have potential for use as a therapeutic option for spinal cord injuries.

Neuroprotective Effects of Autophagy Induced by Rapamycin in Rat Acute Spinal Cord Injury Model

Background/Aims: To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture. Methods: SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale. Results: The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis. Conclusions: The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI.

Effect of Infliximab Combined With Methylprednisolone on Expressions of NF-κB, TRADD, and FADD in Rat Acute Spinal Cord Injury

The possibility to prevent acute spinal cord injury (ASCI) by selective infliximab combined with methylprednisolone (MP) was assessed in experimental ASCI. To investigate the effects of infliximab, MP, and the combination of these 2 agents on expressions of NF-κB (nuclear factor Kappa B), TRADD (tumor necrosis factor receptor associated death domain), and FADD (fas associated death domain) in a rat model of acute spinal cord injury (ASCI), and to confirm the therapeutic efficacy and possible mechanism of infliximab combined with MP in the treatment of ASCI. The theory that SCI can induce tumor necrosis factor-α expression at the injury site has been evaluated. However, there are few data to confirm the therapeutic efficacy of infliximab combinated with MP in the treatment of rat SCI METHODS: One hundred eighty adult male Sprague Dawley rats with 280 to 300 g body weight were allocated randomly and accordingly. We applied Basso, Beattie, Bresnahan locomotor rating scale to assess the hindlimb motor functional score (10 rats × 6 groups), the hematoxylin and eosin stain and immunohistochemistry stain (10 rats × 6 groups) to assay the morphological changes of spinal cord, the arrangement and expressions of NF-κB, TRADD and FADD, and the RT-PCR (10 rats × 6 groups) to evaluate the messenger RNA expressions of NF-κB, TRADD, and FADD. The results showed that both infliximab and MP could lower the expressions of NF-κB, TRADD, and FADD 24 hours after the ASCI, and increased Basso, Beattie, Bresnahan score on the 14th and the 21st days after ASCI, suggesting possible neuroprotective effectiveness on attenuating the severity of neurological deficits and improving the locomotor function in the rat ASCI model. Moreover, infliximab combined with MP exhibited the more powerful ability to this amelioration. Infliximab combined with methylprednisolone may be an effective treatment for the recovery of ASCI. Further study is needed to determine if this neuroprotective effect is seen for long-term outcomes especially in human ASCI.

Muscle atrophy produced by spinal cord injury (SCI) in rats decreases muscle protein synthesis without altering mTOR kinase activity

SCI produces muscle atrophy and derangements in nutrient homeostasis; however, the mechanisms and temporal patterning of these co‐morbidities are poorly defined. Chronic (≥10 week) SCI has been shown to down‐regulate mTOR/S6K1 signaling in soleus muscle and induce changes in body composition and lipid compartmentalization. We assessed muscle protein synthesis (MPS) and degradation in adult rats using an acute contusion injury model at spinal T3. At 7‐days post‐SCI, lean body and gastrocnemius mass were reduced (15% and 20%, respectively), compared to time‐matched controls. In vivo analysis determined this response was mediated, in part, by a 15% decrease in MPS. Contrary to expectations, phosphorylation of AKT (upstream regulator of mTOR) as well as S6K1 and 4E‐BP1 (downstream mediators of mTOR) was not reduced in muscle after SCI, compared to time‐matched sham controls. SCI tended to increase the muscle‐specific E3 ligases atrogin‐1 and MuRF1, but these changes were not statistically significant. REDD1 was also not increased following SCI. Our data suggest acute SCI in rats produces muscle atrophy primarily by reducing MPS may be mTOR‐independent. (Supported by GM38032 and NS49177)

Human Mesenchymal Precursor Cells (Stro-1+) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model

This study aimed to determine the potential of purified (Stro-1(+)) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone marrow (BM) stroma of SCI patients and transplanted as a suspension graft in medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive anatomical analysis shows statistically significant improvement in functional recovery, tissue sparing, and cyst reduction. We provide quantitative assessment of supraspinal projections in combination with functional outcomes. hMPC-transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks post injury. Quantitative histological staining revealed that graft-recipient animals possessed more intact spinal tissue and reduced cyst formation than controls. Fluorogold (FG) retrograde tracing revealed sparing/regeneration of supraspinal and local propriospinal axonal pathways, but no statistical differences were observed compared to controls. Immunohistochemical analysis revealed increased serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding transplanted donor hMPCs 2 weeks posttransplantation, but no evidence of hMPC transdifferentiation was seen. Although hMPCs initially survive at 2 weeks posttransplantation, their numbers were dramatically reduced and no cells were detected at 8 weeks posttransplantation using retroviral/lentiviral GFP labeling and a human nuclear antigen (HNA) antibody. Additional immunosuppression with CsA did not improve hMPC survival or their ability to promote tissue sparing or functional recovery. We propose Stro-1(+)-selected hMPCs provide (i) a reproducible source for stem cell transplantation for SC therapy and (ii) a positive host microenvironment resulting in the promotion of tissue sparing/repair that subsequently improves behavioral outcomes after SCI. Our results provide a new candidate for consideration as a stem cell therapy for the repair of traumatic CNS injury.

Diminution of Secondary Injury after Administration of Pharmacologic Agents in Acute Spinal Cord Injury Rat Model -Comparison of Statins, Erythropoietin and Polyethylene Glycol-

Diminution of Secondary Injury after Administration of Pharmacologic Agents in Acute Spinal Cord Injury Rat Model -Comparison of Statins, Erythropoietin and Polyethylene Glycol-

Combination of Activated Schwann Cells with Bone Mesenchymal Stem Cells: the Best Cell Strategy for Repair after Spinal Cord Injury in Rats

We aim to explore the repair effect of combined cell therapy using activated Schwann cells (ASCs) and bone mesenchymal stem cells (BMSCs) in traumatic spinal cord injury (SCI) in rats. ASCs and BMSCs were used for combined transplantation to treat acute SCI in rats, both of which can be obtained from SCI patients. ASCs were obtained by prior ligation of saphenous nerve and BMSCs by flush of the marrow cavity with Dulbecco's modified Eagle's medium solution. Our experiment in vitro confirmed that ASCs promoted BMSCs to differentiate into mature neural cells. It also indicates that BMSCs hold the potential to repair CNS injury. ASCs and BMSCs were co-transplanted into the injured epicenter of spinal cord made by the New York University (NYU) impactor machine using a 10 g × 50 mm drop weight. Complete ASCs, BMSCs and Dulbecco's modified Eagle's medium were also transplanted in rats with SCI as a control. Recovery of rat's hindlimb function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating scale and footprint analysis. Changes of neurological potential were recorded by nerve electrophysiologic test. Improvement in the microenvironment of the injured spinal cord was evaluated by hematoxylin and eosin staining, glial fibrillary acidic protein staining, biotinylated dextran amine anterograde tracing and electron microscopy. Using biotinylated dextran amine anterograde tracing, we demonstrated that there were more regenerative axons of corticospinal tract surrounding and passing through the injured cavity to the caudal cord in the ASC-BMSC co-graft group than those in the other three groups, and we also confirmed this further by quantitative analysis. Immunostaining for glial fibrillary acidic protein showed the smallest population of astrocytes in the injury epicenter in the ASC-BMSC group compared with the other three groups. Relatively complete myelin sheaths and organelles were found in the ASC-BMSC group compared with the other three groups under electron microscopy. Effective co-transplantation of ASCs and BMSCs promotes functional recovery in rats' hindlimbs and reduces the formation of glial scar, and remyelinates the injured axons as compared with the other three groups. This conclusion was also supported by the observation of immunohistochemistry staining and electron microscopy, suggesting the possible clinical application for the treatment of spinal injury.

Expression changes of Bcl-2 and Bax in response to FTY720 after acute spinal cord injury in rats

Objective To observe the effect of FTY720 on the expressions of Bcl-2 and Bax protein and explore the neuroprotective effect of FTY720 on neuron after acute spinal cord injury in the rats. Methods A total of 75 SD rats were divided randomly into three groups, ie, the test group （ treated with FTY720）, the injury group （treated with normal saline） and the control group. The test and injury groups were impacted to create Tm0 spinal cord injury （SCI） by Allen＇s method. Both the mRNA and protein expressions of Bcl-2 and Bax in the injured spinal cord section were studied respectively with hematoxylin and eosin （ HE ） staining, immunohistochemical examination and reverse transcription polymerase chain reaction （ RT -PC R） technique at different time points （ at 6 h, 12 h,24 h,3 d and 7 d）. Results The expressions of Bcl-2 and Bax in the test group and the injury group were higher than that in the control group at all time points. Meanwhile, at 12 h, 24 h, 3 d and 7 d, the mRNA and protein expressions of Bel-2 in the test group were significantly higher than that in the injury group （ P 〈 0.05 ）, while the mRNA and protein expressions of Bax in the test group were obviously lower than that in the injury group （ P 〈 0.05 ）. Conclusion Early administration of FTY720 （0.5 mg/kg） after spinal cord injury can increase the mRNA and protein expressions of Bcl-2, decrease the expression of Bax and inhibit neuron apoptosis in the injured spinal cord. Key words: Spinal cord injuries ; Bcl-2 ; Bax; Rats

Low dose Estrogen Prevents Neuronal Degeneration and Microglial Reactivity in an Acute Model of Spinal Cord Injury: Effect of Dosing, Route of Administration, and Therapy Delay

Spinal cord injury (SCI), depending on the severity of injury, leads to neurological dysfunction and paralysis. Methylprednisolone, the only currently available therapy renders limited protection in SCI. Therefore, other therapeutic agents must be tested to maximize neuroprotection and functional recovery. Previous data from our laboratory indicate that estrogen (17β-estradiol) at a high dose may attenuate multiple damaging pathways involved in SCI and improve locomotor outcome. Since use of high dose estrogen may have detrimental side effects and therefore may never be used in the clinic, the current study investigated the efficacy of this steroid hormone at very low doses in SCI. In particular, we tested the impact of dosing (1-10 μg/kg), mode of delivery (intravenous vs. osmotic pump), and delay in estrogen application (15 min-4 h post-SCI) on microgliosis and neuronal death in acute SCI in rats. Treatment with 17β-estradiol (1-10 μg/kg) significantly reduced microglial activation and also attenuated apoptosis of neurons compared to untreated SCI animals. The attenuation of cell death and inflammation by estrogen was observed regardless of mode and time of delivery following injury. These findings suggest estrogen as a potential agent for the treatment of individuals with SCI.

Insulin with Chondroitinase ABC Treats the Rat Model of Acute Spinal Cord Injury

Traumatic brain injury is often associated with acute spinal cord injury (ASCI). Insulin and chondroitinase ABC (ChABC) are both therapeutically effective, but the combined therapeutic effect of insulin and ChABC is still not clear. A combination of insulin and ChABC were used to treat a rat model of ASCI. This combination therapy prevented neuronal cell death by improving motor function, increasing cell growth and inhibiting cell apoptosis in ASCI rats. Expression of growth-associated protein 43, a marker of axonal re-growth, increased after combined treatment with insulin and ChABC. These results may provide a basis for a future method of treating ASCI.

Effects of Methylprednisolone and Hyperbaric Oxygen on Oxidative Status after Experimental Spinal Cord Injury: A Comparative Study in Rats

The effects of hyperbaric oxygen (HBO) therapy or methylprednisolone on the oxidative status were evaluated in experimental spinal cord injury. Clip compression method was used to produce acute spinal cord injury rats. Hyperbaric oxygen was administered twice daily for a total of eight 90 min-sessions at 2.8 atmospheres. Methylprednisolone was first injected with a bolus of 30 mg/kg followed with an infusion rate of 5.4 mg/kg/h for 24 h. Five days after clip application animals were sacrificed and their traumatized spinal cord segment were excised. Tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated to reflect oxidant/antioxidant status. Non-treated clip-operated animals reflected significantly higher SOD, GSH-Px and TBARS levels that were found to be significantly higher than the sham-operated. Methylprednisolone was not able to lower these levels. HBO administration diminished all measured parameters significantly; however, their levels appeared already to be high when compared with sham animals. According to these results obtained on the 5th day after induction, HBO, but not methylprednisolone, seems to procure prevention against oxidative spinal cord injury.