Model Of Spinal Cord Trauma Research Articles

Effects of lercanidipine on traumatic spinal cord injury: an experimental study.

Spinal cord injury is a devastating trauma that leaves survivors at risk for several medical complications throughout their lives. Lercanidipine, a third-generation calcium channel blocker, possesses anti-apoptotic, anti-inflammatory, and antioxidative properties. This study aimed to evaluate the neuroprotective effects of lercanidipine in an experimental spinal cord trauma model. Twenty-one Wistar rats were randomly assigned to three groups. Group 1 (G1) underwent laminectomy. Group 2 (G2) were subjected to trauma following laminectomy. Group 3 (G3) were exposed to trauma following laminectomy and treated with lercanidipine. Lercanidipine was administered intraperitoneally for seven days. Histopathological and immunohistochemical evaluations were conducted. Regarding Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, there was no significant difference among the groups. However, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) levels were significantly different across the groups. G2 had significantly higher NF-κB levels compared to G1 and G3. Lercanidipine, a third-generation calcium channel blocker, is effective against inflammatory responses induced in spinal cord injury. Further studies are required to determine its capability in preventing apoptosis or improving functional recovery. To the best of our knowledge, this study is the first in the literature to examine the neuroprotective effects of lercanidipine on spinal cord injury.

The changes made in the article titled “BIOCHEMICAL ANALYSIS FOR NEUROPROTECTIVE EFFECTS OF GANODERMA LUCIDUM IN EXPERIMENTAL RAT SPINAL CORD TRAUMA MODEL” in the original articles section published in JTSS 2021 32(3) are as follows.

The changes made in the article titled “BIOCHEMICAL ANALYSIS FOR NEUROPROTECTIVE EFFECTS OF GANODERMA LUCIDUM IN EXPERIMENTAL RAT SPINAL CORD TRAUMA MODEL” in the original articles section published in JTSS 2021 32(3) are as follows.

Evaluation of the neuroprotective effects of anti-inflammatory drugs in experimental spinal cord damage.

In this study, we aimed to investigate the effectiveness of etofenamate and compare it with methyl prednisolone in the experimental spinal cord trauma model. A total of 31 Wistar Albino rats weighed between 220 and 270 gr were used in this study. The rats were divided into three groups as the control; posttraumatic normal saline (NS), trauma + E; posttraumatic etofenamate; and trauma + methylprednisolone, posttraumatic methylprednisolone. All medications were given into the peritoneum. Six hours after trauma and drug administration, approximately 2 cm of cord segment in the area subjected to dorsal laminectomy was dissected from the dura spinal cord and removed. The samples were histopathologically examined. In this study, significant differences were found both between trauma + NS and trauma + methylprednisolone, and between trauma NS and trauma + etofenamate, and trauma + methylprednisolone and trauma + etofenamate groups according to the Ivan Damjanov criteria and in terms of petechial hemorrhage, diffuse bleeding, loss in the regulation of grey and white matters, edema, necrosis, and cystic degeneration findings. According to the Ivan Damjanov criteria, trauma + NS group was found as Grades 2-3, trauma + etofenamate group as Grade 1, and trauma + methylprednisolone as Grades 1-2. Neuroprotective effect of etofenamate was found to be stronger than that of methyl prednisolone in rats with induced posttraumatic spinal cord damage (Tab. 4, Ref. 24). Keywords: etofenamate, methylprednisolone, spinal trauma, rats.

Investigation of the Effect of Alemtuzumab in an Experimental Spinal Cord Trauma Model in Rats

Spinal cord injuries generate the most negative response to medical treatment among all general body injuries. This important morbidity is thought to be caused by a complex secondary damage mechanism. In the present study, we examined the neuroprotective effects of alemtuzumab in a spinal cord trauma model. We divided 24 Long-Evans male rats into 4 groups (n= 6 per group). Laminectomy was performed at T5-T8 in all groups. Trauma was applied using the Yasargil temporary aneurysm clip for 60 seconds at these spinal cord levels in all groups, except for group 1. Next, 1 mg/kg of alemtuzumab was administered to each rat in groups 3 and 4. A functional evaluation was performed on days 1, 3, and 5 in groups 1, 2, and 4, and the rats were then sacrificed. The rats in group 3 were sacrificed on the third postoperative day to observe the early effects of alemtuzumab. The biochemical examination findings of malondialdehyde and glutathione in plasma and tissue samples and histopathological findings of the spinal cord were evaluated and compared by statistical analysis. The inflammatory findings in the trauma group were not seen in either group treated with alemtuzumab. The clinical motor examination and inclined plane test results were also significantly better in these groups. Our results have shown that alemtuzumab might prevent spinal cord injury after trauma and is a histopathologically and biochemically strong anti-inflammatory, antioxidant, and neuroprotective agent.

Artificial Zinc-Finger Transcription Factor of A20 Suppresses Restenosis in Sprague Dawley Rats after Carotid Injury via the PPARα Pathway.

The inhibition of inflammation and vascular smooth muscle cell (VSMC) proliferation is an ideal strategy to suppress intimal hyperplasia after percutaneous transluminal angioplasty (PTA). Evidence has indicated that overexpression of A20 suppresses neointima formation, but its low transfection efficiency limits its application. Hence, we upregulated A20 expression via transfection of rAd.ATF (recombinant adenovirus vector of artificial transcription factor) and rAd.A20 in rat carotid arteries after balloon dilatation (in vivo) and isolated VSMCs (in vitro). In vivo, we found that after rAd.ATF and rAd.A20 transfection, A20 expression was markedly increased, whereas proliferating cell nuclear antigen (PCNA) and nuclear factor κB p65 (NF-κBp65) protein levels were significantly decreased, and intimal hyperplasia and secretion of proinflammatory factors were significantly reduced when compared with empty vector and saline control groups. Most importantly, the rAd.ATF-treated group showed more significant inhibition on intimal hyperplasia and expression of PCNA than the rAd.A20-treated group. In vitro, compared with the control group, transfection of rAd.ATF and rAd.A20 significantly increased A20 expression, which upregulated the proliferator-activated receptor (PPAR) level for both mRNA and protein, and reduced migration and proliferation of VSMCs and lipopolysaccharide (LPS)-induced inflammation. Furthermore, the PPARα agonist GW6471 could partially restore the effect of A20 on VSMCs. Our findings indicate that the ATF of A20 inhibits neointimal hyperplasia and, therefore, constitutes a novel potential alternative to prevent restenosis.

Deletion of mammalian sterile 20-like kinase 1 attenuates neuronal loss and improves locomotor function in a mouse model of spinal cord trauma.

Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score. Deletion of Mst1 in mice attenuated loss of motor neurons and suppressed microglial and glial activation following SCI. Deletion of Mst1 in mice reduced apoptosis via suppressing cytochrome c release and caspase-3 activation following SCI. Deletion of Mst1 attenuated mitochondrial dysfunction and increased ATP formation following SCI. Deletion of Mst1 in mice inhibited local inflammation following SCI, evidenced by reduced activities of myeloperoxidase and protein levels of TNF-α, IL-1β, and IL-6. In conclusion, the present study demonstrated that deletion of Mst1 attenuated neuronal loss and improved locomotor function in a mouse model of SCI, via preserving mitochondrial function, attenuating mitochondria-mediated apoptotic pathway, and suppressing inflammation, at least in part.

PPAR-α Modulates the Anti-Inflammatory Effect of Melatonin in the Secondary Events of Spinal Cord Injury.

Melatonin is the principal secretory product of the pineal gland, and its role as an immunomodulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and reduces the development of inflammation and tissue injury events associated with spinal cord trauma. Previous results suggest that peroxisome proliferator-activated receptor α (PPAR-α), a nuclear receptor protein that functions as a transcription factor activated by fatty acids, plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI).With the aim to characterize the role of PPAR-α in melatonin-mediated anti-inflammatory activity, we tested the efficacy of melatonin (30mg/kg) in an experimental model of spinal cord trauma, induced in mice, by the application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-α KO) with wild-type (WT) mice.The results obtained indicate that melatonin-mediated anti-inflammatory activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, melatonin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, pro-inflammatory cytokine expression, nuclear factor κB (NF-κB) activation, and inducible nitric oxide synthase (iNOS) expression. This study indicates that PPAR-α can contribute to the anti-inflammatory activity of melatonin in SCI.

Rat Spinal Cord Injury Experimental Model

Abstract Spinal cord injuries (SCI) with their tragic consequences belong to the most serious pathological conditions. That is why they have stimulated basic research workers, as well as health care practitioners, to search for an effective treatment for decades. Animal experimental models have been essential in these efforts. We have jointly decided to test and standardize one of the spinal cord injury compression models in rats. Twentythree adult female Wistar rats weighing 250-320 g were utilized. Employing general anaesthesia along with a mixture of sevoflurane with O2, 2 rats (sham controls) had their vertebral arch of either Th8 or Th9 vertebra removed (laminectomy). The other 21 experimental rats with similar laminectomies were divided into 3 subgroups (n = 7) which received compression impact forces of 30, 40 or 50 g (subgroups-1, -2, and -3, respectively) applied on their exposed spinal medulla for 15 minutes. All rats were observed for 28 days after the experimental procedure and their motor functions were assessed by the Basso, Beattie, Bresnahan (BBB) test 6 hours, 7, 21 and 28 days after the simulated SCI. All 23 rats survived the surgical procedures. The control rats were without any neurological deficits. There were, in every experimental subgroup, 1 or 2 rats with extreme BBB scores. So the rats with the maximum and minimum BBB values were excluded. Then, the results acquired in the residual 5 rats in each group were averaged and statistically analysed by the Tukey multiple comparisons test. Statistically significant intersubgroup differences were found at all survival times equal to or longer than 7 post SCI days. The goal of the SCI experiment was to generate a reproducible and reliable, submaximal spinal cord trauma model. The statistical analyses demonstrated that this objective was best achieved in the subgroup-2 with the 40 g compression.

Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor huperzine A in an experimental spinal cord trauma model.

Spinal cord injury is nowadays still a challenging disease, and a treatment option aimed at the primary site of injury does not currently exist. Therefore, the management of acute spinal cord injury has recently focused on the reasons behind the aggravation of the initial insult through secondary mechanisms, and the search for pharmacological treatment protocols is generally aimed at reducing and minimizing the neural injury and neurological sequela. The secondary spinal cord injury usually develops following a primary lesion induced by spinal cord contusion and the emergence of apoptotic cells has been found to play an important role in the development of secondary injury. We propose that huperzine A may induce a significant reduction in the number of apoptotic cells because it possesses the ability to protect cells against glutamate, ischemia and staurosporine-induced cytotocity and apoptosis. Huperzine A was administered intraperitoneally to male Wistar Albino rats (220-340 g of body weight) after moderate static clip compression (70 g for 60 s) of the spinal cord at T7 level. Neurological functions were assessed using the Basso-Beattle-Breshanan (BBB) motor rating scale until 3th and 7th days before perfusion, following which the spinal cord was harvested for histopathological examinations and apoptotic cell counts. Histopathological evaluations of the spinal cord of the control, trauma and huperzine A treated groups were evaluated. Control group showed normal neuronal and vascular structures of the spinal cord. However, in both trauma groups 3rd- and 7th-day perfusion showed extensive cavitation and hemorrhage, areas of necrosis and edema in gray matter, and degeneration in motor neurons along with patchy areas of necrotic and apoptotic cells. In the group treated with huperzine A, an increased number of normal cells was observed, along with a lower number of necrotic cells, with a significant reduction in the apoptotic cells (P<0.01). The administration of huperzine A improved post-trauma motor performance. Furthermore, BBB scores of all groups showed that there was an improvement of locomotor abilities in the treatment group as compared with the control. When compared with controls, huperzine A treatment demonstrates a significant reduction in the number of apoptotic cells. In addition, the group treated with huperzine A showed significant and appreciable neurological improvement in rats.

Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats

IntroductionGanoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Materials and methodsRats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. ResultsAfter traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. ConclusionsBiochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury.

The Investigation of Neuroprotective Effects of Aminoguanidin and N-Acetylcystein administration alone and combination in Spinal Cord Trauma model

The Investigation of Neuroprotective Effects of Aminoguanidin and N-Acetylcystein administration alone and combination in Spinal Cord Trauma model

Neuroprotective effects of rosuvastatin against traumatic spinal cord injury in rats

Rosuvastatin, which is a potent statin, has never been studied in traumatic spinal cord injury. The aim of this study was to investigate whether rosuvastatin treatment could protect the spinal cord after experimental spinal cord injury. Rats were randomized into the following five groups of eight animals each: control, sham, trauma, rosuvastatin, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumor necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analyzed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test.After traumatic spinal cord injury, increases in caspase-3 activity, tumor necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. In contrast, the superoxide dismutase levels were decreased. After the administration of rosuvastatin, decreases were observed in the tissue caspase-3 activity, tumor necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. In contrast, tissue superoxide dismutase levels were increased. Furthermore, rosuvastatin treatment showed improved results concerning the histopathological scores, the ultrastructural score and the functional tests. Biochemical, histopathological, ultrastructural analysis and functional tests revealed that rosuvastatin exhibits meaningful neuroprotective effects against spinal cord injury.

Assessment of motor recovery and MRI correlates in a porcine spinal cord injury model

The study concentrated on behavioral and magnetic resonance imaging (MRI) characteristics in a porcine spinal cord injury model. Six adult minipigs weighing 32–35 kg were narcotized by thiopental, intubated, and placed on a volume-cycled ventilator. Anaesthesia was maintained by 1.5% sevoflurane with oxygen. Following location of the 1st lumbar vertebra animals were fastened in an immobilization frame. The spinal cord, exposed through a laminectomy, was compressed by a 5 mm thick circular rod with a peak force of 0.8 kg at a velocity of 3 cm·s-1. The next day the minipigs were paraplegic but improved rapidly to paraparesis. On the 12th postoperative day they were euthanasied. Neural tissue changes were evaluated by post mortem MRI, which showed damage to the spinal cord white and/or gray matter in the epicentre of compression with longitudinal spreading over one segment cranially and caudally. Statistical analyses performed by Spearman’s rho test revealed positive correlations between damaged areas and the whole area of the spinal cord white/gray matter (P = 0.047; rs = 0.742) and (P = 0.002; rs = 0.943), respectively. The study confirmed the reliability and reproducibility of the utilised model of spinal cord trauma. The structural changes in the epicentre of injury did not impede the rapid but incomplete recovery of motor functions.

Glia and Mast Cells as Targets for Palmitoylethanolamide, an Anti-inflammatory and Neuroprotective Lipid Mediator

Glia are key players in a number of nervous system disorders. Besides releasing glial and neuronal signaling molecules directed to cellular homeostasis, glia respond also to pro-inflammatory signals released from immune-related cells, with the mast cell being of particular interest. A proposed mast cell-glia communication may open new perspectives for designing therapies to target neuroinflammation by differentially modulating activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can be upregulated as a result of tissue damage or stimulation of inflammatory responses. Such molecules include the N-acylethanolamines, whose principal family members are the endocannabinoid N-arachidonoylethanolamine (anandamide), and its congeners N-stearoylethanolamine, N-oleoylethanolamine, and N-palmitoylethanolamine (PEA). A key role of PEA may be to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation: PEA is produced and hydrolyzed by microglia, it downmodulates mast cell activation, it increases in glutamate-treated neocortical neurons ex vivo and in injured cortex, and PEA levels increase in the spinal cord of mice with chronic relapsing experimental allergic encephalomyelitis. Applied exogenously, PEA has proven efficacious in mast cell-mediated experimental models of acute and neurogenic inflammation. This fatty acid amide possesses also neuroprotective effects, for example, in a model of spinal cord trauma, in a delayed post-glutamate paradigm of excitotoxic death, and against amyloid β-peptide-induced learning and memory impairment in mice. These actions may be mediated by PEA acting through "receptor pleiotropism," i.e., both direct and indirect interactions of PEA with different receptor targets, e.g., cannabinoid CB2 and peroxisome proliferator-activated receptor-alpha.

AR-A014418 as a glycogen synthase kinase-3 inhibitor: Anti-apoptotic and therapeutic potential in experimental spinal cord injury

We aimed to investigate the effects of AR-A014418, a strong inhibitor specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic SCI model. In this study, three groups were generated from 36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip compression technique after laminectomy, and (3) AR-A014418 (4mg/kg, i.p., DMSO) treatment group after laminectomy and spinal cord trauma. The TUNEL assay for apoptosis detection, immunohistochemical staining for bax and TGF-beta were applied in spinal cord tissues. For light microscopic examination, necrotic, and apoptotic cells were counted, and PMNL counting was applied to detect inflammation. Functional recovery was tested by field locomotor test in the 3rd and 7th days following surgery. In the trauma group, diffuse hemorrhage, cavitation, necrosis and edematous regions, degeneration in motor neurons and leukocyte infiltration were observed in gray matter. In the AR-A014418-treated groups, healthy cells were observed in more places compared to the trauma groups, however, cavitation, hemorrhagic, and edematous areas were seen in gray matter. In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and 7th days (respectively; p<0.05, p<0.01), were significantly decreased compared to the trauma groups, as were the levels of bax (p<0.01) and TGF-beta 1 immunoreactivity. Results of the locomotor test were significantly increased in the treatment group (p<0.001) as compared to the trauma group. In this experimental spinal cord trauma model study neural apoptosis was significantly triggered in secondary damage developed after trauma, however, neurological healing was expedited by preventing mitochondrial apoptosis and reducing the inflammation by the potent inhibitor AR-A014418, which is GSK-3beta selective.

Effect of Fasudil, a Selective Inhibitor of Rho Kinase Activity, in the Secondary Injury Associated with the Experimental Model of Spinal Cord Trauma

Rho kinase (ROK) may play an important role in regulating the biological events of cells, including proliferation, differentiation, and survival/death. Blockade of ROK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. The aim of this experimental study was to determine the role of ROK signaling pathways in the inflammatory response, in particular in the secondary injury associated with the experimental model of spinal cord trauma. The injury was induced by application of vascular clips to the dura via a four-level T5 to T8 laminectomy in mice. Fasudil was administered in mice (10 mg/kg i.p.) 1 and 6 h after the trauma. The treatment with fasudil significantly decreased 1) histological damage; 2) motor recovery; 3) nuclear factor-κB (NF-κB) expression; 4) ROK activity; 5) inflammasome activation (caspase-1 and NOD-like receptor family, pyrin domain-containing 3 expression); 6) production of proinflammatory cytokine such as tumor necrosis factor and interleukin-1β (IL-1β); 7) neutrophil infiltration; 8) nitrotyrosine and poly-ADP-ribose formation; 9) glial fibrillary acidic protein expression; 10) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, FAS ligand expression, and Bax and Bcl-2 expression); and 11) mitogen-activated protein kinase activation (phospho-extracellular signal-regulated kinase and phospho-c-Jun NH(2)-terminal kinase expression). Our results indicate that inhibition of ROK by fasudil may represent a useful therapeutic perspective in the treatment of inflammation associated with spinal cord trauma.

Anti-inflammatory effect of simvastatin in an experimental model of spinal cord trauma: involvement of PPAR-α

BackgroundStatins such as simvastatin are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase used in the prevention of cardiovascular disease. In addition to their cholesterol-lowering activities, statins exert pleiotropic anti-inflammatory effects, which might contribute to their beneficial effects on lipid-unrelated inflammatory diseases. Recently it has been demonstrated that the peroxisome proliferator-activated receptor (PPAR)-α mediates anti-inflammatory effects of simvastatin in vivo models of acute inflammation. Moreover, previous results suggest that PPAR-α plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI).MethodsWith the aim to characterize the role of PPAR-α in simvastatin activity, we tested the efficacy of simvastatin (10 mg/kg dissolved in saline i.p. 1 h and 6 h after the trauma) in an experimental model of SCI induced in mice by extradural compression of the spinal cord (T6-T7 level) using an aneurysm clip with a closing force of 24 g via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-α KO) with wild type (WT) mice. In order to elucidate whether the effects of simvastatin are due to activation of the PPAR-α, we also investigated the effect of a PPAR-α antagonist, GW6471 (1 mg/kg administered i.p. 30 min prior treatment with simvastatin) on the protective effects of on simvastatin.ResultsResults indicate that simvastatin activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, simvastatin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation, neutrophil infiltration, nitrotyrosine formation, pro-inflammmatory cytokine expression, nuclear factor (NF)-κB activation, inducible nitric-oxide synthase (iNOS) expression, and apoptosis. In addition we demonstrated that GW6471 significantly antagonized the effect of the statin and thus abolished the protective effect.ConclusionsThis study indicates that PPAR-α can contribute to the anti-inflammatory activity of simvastatin in SCI.

The effects of a polyphenol present in olive oil, oleuropein aglycone, in an experimental model of spinal cord injury in mice

Several olive oil phenolic compounds, such us oleuropein have attracted considerable attention because of their antioxidant activity, anti-atherosclerotic and anti-inflammatory properties. The aim of this experimental study was to determine the effect of oleuropein aglycone, a hydrolysis product of oleuropein, in the inflammatory response, in particular in the secondary injury associated with the mouse model of spinal cord trauma. The injury was induced by application of vascular clips to the dura via a four-level T5–T8 laminectomy in mice. Oleuropein aglycone was administered in mice (100μg/kg, 40μg/kg, 20μg/kg, 10% ethanol, i.p.) 1h and 6h after the trauma. The treatment with oleuropein aglycone significantly decreased: (1) histological damage, (2) motor recovery, (3) nuclear factor (NF)-κB expression and IKB-α degradation, (4) protein kinase A (PKA) activity and expression, (5) pro-inflammatory cytokines production such as tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β), 6) inducible nitric oxide synthase (iNOS) expression, (7) neutrophil infiltration, (8) lipid peroxidation, (9) nitrotyrosine and poly-ADP-ribose (PAR) formation, (10) glial cell-derived neurotrophic factor (GDNF) levels, (11) apoptosis (TUNEL staining, FAS ligand expression, Caspase 3, Bax and Bcl-2 expression). Thus, we propose that olive oil phenolic constituents such as oleuropein aglycone may be useful in the treatment of various inflammatory diseases.

MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma

BackgroundGlutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy.ResultsSpinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis. In this study we clearly demonstrated that administration of MK801 attenuated all inflammatory parameters. In fact 24 hours after injury, the degree of spinal cord inflammation and tissue injury (evaluated as histological score), infiltration of neutrophils, NF-κB activation, iNOS, cytokines levels (TNF-α and IL-1β), neurotrophin expression were markedly reduced by MK801 treatment. Moreover, in a separate set of experiments, we have demonstrated that MK801 treatment significantly improved the recovery of locomotory function.ConclusionsBlockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury.

Efficacy of treatment with verbascoside, biotechnologically produced by Syringa vulgaris plant cell cultures in an experimental mice model of spinal cord trauma

In this study we evaluated the effect of glycosylated phenylpropanoid verbascoside (VB), isolated from cultured cells of the medicinal plant Syringa vulgaris (Oleaceae) in experimental animal model of spinal cord injury (SCI). SCI was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis. At 1 and 6h after injury, the mice were treated with VB extract, administered at the dose of 2mg/kg with intraperitoneal administration. Immunohistochemical examination demonstrated a marked increase on expression for nitrotyrosine, inducible nitric oxide synthase, poly(ADP-ribose), and apoptosis events (increase of Bax and Bcl-2 expression) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the cytokines expression (TNF-α and IL-1β), neutrophil infiltration (myeloperoxidase), and activation of NF-κB. In contrast, all of these parameters of inflammation were attenuated by treatment with VB. In a separate set of experiment, we have clearly demonstrated that VB treatment significantly ameliorated the recovery of function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with VB extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma.