Topiramate as a neuroprotective agent in a rat model of spinal cord injury.

Topiramate (TPM) is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury (SCI). After rat models of thoracic contusive SCI were established by free weight-drop method, TPM (40 mg/kg) was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.

The effect of HDL-bound and free PON1 on copper-induced LDL oxidation.

Oxidative modification of LDL plays an important role in the development of atherosclerosis. High-density lipoprotein (HDL) confers protection against atherosclerosis and the antioxidative properties of paraoxonase 1 (PON1) has been suggested to contribute to this effect of HDL. The PON1 exist in two major polymorphic forms (Q and R), which regulate the concentration and activity of the enzyme and alter its ability to prevent lipid oxidation. However, the association of Q192R polymorphism with PON1's capacity to protect against LDL lipoperoxidation is controversial. The aim of this study was to evaluate the effects of the purified PON1 Q192R and the partially purified HDL-bound PON1 Q192R isoenzymes (HDL-PON1 Q192R) on LDL oxidation, with respect to their arylesterase/homocysteine thiolactonase (HTLase) activities. Cupric ion-induced LDL oxidation was reduced up to 48% by purified PON1 Q192, but only 33% by an equivalent activity of PON1 R192. HDL-PON1 Q192 isoenzyme caused a 65% reduction, whereas HDL-PON1 R192 isoenzyme caused only 46% reduction in copper ion-induced LDL oxidation. These findings reflect the fact that PON1 Q and PON1 R allozymes may have different protective characteristics against LDL oxidation. The protection against LDL oxidation provided by HDL-PON1 Q192R isoenzymes is more prominent than the purified soluble enzymes. Inhibition of the Ca(+2)-dependent PON1 Q192R arylesterase/HTLase by the metal chelator EDTA, did not alter PON1's ability to inhibit LDL oxidation. These studies indicate that the active site involvement of the purified enzyme is not similar to the HDL-bound one, in terms of both PON1 arylesterase/HTLase activity and the protection of LDL from copper ion-induced oxidation. Moreover, PON1's ability to protect LDL from oxidation does not seem to require calcium.

Using Salivary Nitrite and Nitrate Levels as a Biomarker for Drug-Induced Gingival Overgrowth.

AIM: Drug-induced gingival overgrowth has a multifactorial nature and the pathogenesis is still uncertain. It has been suggested that Nitric Oxide (NO) might play a role in the pathogenesis of drug-induced gingival overgrowth due to the contribution of NO to immune response and matrix degradation. NO levels in biological fluids have been used as a diagnostic biomarker in many diseases. The aim of this study is to determine whether NO levels in plasma, saliva, and gingival crevicular fluid (GCF) can serve as a potential biomarker for the evaluation of drug-induced gingival overgrowth risk. MATERIALS AND METHODS: A total of 104 patients, receiving cyclosporine A (n = 35), phenytoin (n = 25), nifedipine (n = 26), or diltiazem (n = 18) participated in the study. The amount of gingival overgrowth was evaluated with two indices and was given as percentage. Periodontal clinical parameters including plaque index (PI), gingival index (GI), gingival bleeding time index (GBTI), and probing depth (PD) were also assessed. Saliva, GCF, and plasma samples were obtained from each participants. Nitrite and nitrate levels in saliva, GCF, and plasma were analyzed by Griess reagent. RESULTS: Salivary nitrite and nitrate levels in responders were significantly higher than those in non-responders in only phenytoin group (p < 0.05). Nitrite and nitrate levels of gingival crevicular fluid and plasma did not significantly differ between responders and non-responders in all study groups (p > 0.05). Salivary nitrite levels exhibited a significant correlation with PD, GBTI, severity of gingival overgrowth (%GO), and GCF volume (p < 0.05). Additionally, a strong positive correlation was detected between saliva and plasma nitrate levels (p < 0.005). However, both nitrite and nitrate levels in GCF and plasma demonstrated no significant correlation with clinical parameters, GO severity, and GCF volume (p > 0.05). CONCLUSION: Salivary nitrite and nitrate levels could be used as periodontal disease biomarkers in phenytoin induced gingival overgrowth, and that saliva seems to have a better diagnostic potential than GCF and plasma for the evaluation of drug-induced gingival overgrowth risk. However, when all drug groups were considered, saliva nitrite and nitrate levels could not be used as a biomarker for drug-induced gingival overgrowth.

Evaluation of Oxidative Metabolism in Child and Adolescent Patients with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: Oxidative metabolism is impaired in several medical conditions including psychiatric disorders, and this imbalance may be involved in the etiology of these diseases. The present study evaluated oxidative balance in pediatric and adolescent patients with attention deficit hyperactivity disorder (ADHD). METHODS: The study included 48 children and adolescents (34 male, 14 female) with ADHD who had no neurological, systemic, or comorbid psychiatric disorders, with the exception of oppositional defiant disorder (ODD), and 24 sex- and age-matched healthy controls (17 male and seven female). RESULTS: TAS was significantly lower, and TOS and OSI were significantly higher in patients with ADHD than in healthy controls. Total antioxidant levels were lower in patients with comorbid ODD than in those with no comorbidity. No difference was found in TOS or OSI among the ADHD subtypes; however, TAS was higher in the attention-deficient subtype. CONCLUSION: Our findings demonstrated that oxidative balance is impaired and oxidative stress is increased in children and adolescents with ADHD. This results are consistent with those of previous studies.

Nitrite and nitrate levels of gingival crevicular fluid and saliva in subjects with gingivitis and chronic periodontitis.

OBJECTIVES: Nitrosative stress plays an essential role in the pathogenesis of periodontal disease. The aim of this study is to analyze the gingival crevicular fluid and saliva nitrite and nitrate levels in periodontally healthy and diseased sites. MATERIAL AND METHODS: A total of 60 individuals including, 20 chronic periodontitis and 20 gingivitis patients and 20 periodontally healthy controls participated in the present study. Probing depth, clinical attachment level, bleeding on probing, gingival index and plaque index were assessed, gingival crevicular fluid (GCF) and saliva samples were obtained from the subjects, including 480 GCF samples and 60 unstimulated whole saliva samples. Nitrite and nitrate were analyzed by Griess reagent. RESULTS: Total GCF nitrite levels were higher in gingivitis and periodontitis groups (1.07 [SD 0.62] nmol and 1.08 [SD 0.59] nmol) than the control group (0.83 [SD 0.31] nmol) (P < 0.05) but did not differ significantly between gingivitis and periodontitis groups (P > 0.05). The difference in GCF nitrate level was not significant among the control, gingivitis and periodontitis groups (7.7 [SD 2.71] nmol, 7.51 [SD 4.16] nmol and 7.38 [SD 1.91] nmol). Saliva nitrite and nitrate levels did not differ significantly among three study groups. Saliva nitrate/nitrite ratios were higher in periodontitis and gingivitis groups than the control group. A gradual decrease in nitrate/nitrite ratio in GCF was detected with the presence of inflammation. CONCLUSIONS: It may be suggested that nitrite in gingival crevicular fluid is a better periodontal disease marker than nitrate and may be used as an early detection marker of periodontal inflammation, and that local nitrosative stress markers don't show significant difference between the initial and advanced stages of periodontal disease.

Mucopolysaccharidosis: Otolaryngologic findings, obstructive sleep apnea and accumulation of glucosaminoglycans in lymphatic tissue of the upper airway.

OBJECTIVE: The aim of this study is to evaluate otolaryngologic problems (upper airway obstruction, obstructive sleep apnea, restriction of mouth opening, middle ear effusion, hearing and breathing problems) and their treatments on mucopolysaccharidoses (MPS) patients and to investigate accumulation of glucosaminoglycans (GAG) in the upper airway biochemically and pathologically. METHODS: 76 MPS patients were evaluated. Forty-two MPS patients underwent polysomnography (PSG) for obstructive sleep apnea (OSA). Pre- and postoperative PSG results of 18 patients were compared. The success and complications of treatments for OSA in MPS were evaluated. Biochemical and histopathological accumulation of GAG in tonsil and adenoid tissue and middle ear effusion were analyzed and compared with the control group. RESULTS: Forty patients out of 42 tested with PSG had OSA (95%). Adenoid grade, Mallampati grade, restricted mouth opening, rate of difficult intubation were significantly different among MPS subtypes. MPS types III and IV had significantly lower Mallampati scores; type VI had significantly worse mouth opening; and type III had significantly better mouth opening and higher rate of easy intubation when compared to other MPS types. There was no significant difference between MPS subtypes according to tonsil grade, adenoid grade, rate of otitis media with effusion and OSA severity. Statistically significant difference was found between GAG accumulation in adenoid tissue and middle ear effusion of MPS and control group (p<0.05). However, GAG accumulation in tonsil was not significantly different between MPS and control group. There was a statistically significant improvement in postop Apnea-Hypopnea Index (AHI) compared to preop AHI (p<0.05). CONCLUSIONS: Most MPS patients have airway obstruction and OSA due to adenotonsillar hypertrophy. Most of these children benefit from adenotonsillectomy, after which OSA significantly improves. They experience high recurrence rate after adenoidectomy; though this is not clinically problematic. They also suffer from conductive hearing loss due to OME, which has to be treated with ventilation tube insertion. However, such operations are usually complicated by difficult endotracheal intubation and restricted mouth opening. Sometimes tracheotomy may be necessary. Tracheotomy is also highly complicated in MPS patients. Significant accumulation of GAG in middle ear fluid and adenoid tissue is present; however, GAG appears not to accumulate in tonsillar tissue.

The influence of platform switching on clinical, laboratory, and image-based measures: a prospective clinical study.

PURPOSE: This prospective study was conducted to compare the marginal bone level alterations, stability/mobility measurements, and volume of myeloperoxidase (MPO) and nitric oxide (NO) of peri-implant sulcus fluid (PISF) between platform-switched (PS) and standard platform (SP) implants inserted to mandibular premolar/molar regions with a single-stage protocol. MATERIALS AND METHODS: Thirty-two (16 PS and 16 SP) implants restorated with fixed prosthesis were included in the study. For both implant systems standard implant dimensions were used. Implant abutment connections and final restorations were made after 3 months of osseointegration. Standard parallel periapical radiographs were used to measure marginal bone loss in over time. Resonance frequency analysis (RFA) and mobility measuring (MM) device were used to determine implant stability/mobility. PISF samples were derived with paper strips and PISF MPO and nitrite level analysis were done spectrophotometrically. Peri-implant parameters were assessed by periodontal indices and all parameters were evaluated at baseline, 1, 3, 6, and 12 months follow-up. RESULTS: No healing problems were recorded for all implants at the end of the study period. At 12 months, mean bone loss measures were 0.84 and 0.76 mm, and mean implant stability quotient (ISQ) values were 74.04 and 76 for PS and SP implants, respectively. Mean MM values were found as -4.82 for PS and -6.26 for SP implants. There were no significant differences between implant types according to PISF volume and laboratory biochemical measures including MPO and NO, and clinical peri- implant indices at any time point. CONCLUSION: Platform switching seems not to affect the marginal bone level, clinical peri-implant parameters and MPO and NO metabolism around implants inserted to mandibular premolar/molar regions when using a single-stage protocol.

Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine ischemia in the fetal rat brain: ultrastructural evaluation.

AIM: The aim of this study was to investigate the neuroprotective effect of magnesium sulfate and dexamethasone on oxidative damage in intrauterine ischemia. MATERIAL AND METHODS: In this study, 19-day pregnant rats were divided into five groups. Fetal brain ischemia was achieved in the ischemia/ reperfusion (I/R) group by bilaterally closing the utero-ovarian artery with aneurysm clips for 30 min and subsequently removing the aneurysm clips for 60 min for reperfusion. Mg (600 mg/kg) and dexamethasone (0.25 mg/kg) were administered 20 min before the I/R insult. The lipid peroxidation in the brain tissue was determined by the concentration of thiobarbituric acid reactive substances (TBARS). The mitochondrial score was calculated after an evaluation with electron microscopy. RESULTS: Both the electron microscope and TBARS data showed a significant difference between the control and I/R groups. The Mg and dexamethasone treatment groups exhibited significantly lower TBARS values compared to the IR group. Similarly, the mitochondrial scores in the Mg and dexamethasone treatment groups were significantly lower than those in the I/R group. CONCLUSION: Result showed that magnesium sulfate and dexamethasone prevent lipid peroxidation and reduce mitochondrial injury thus suggests neuroprotective effects in fetal rat brain in intrauterine ischemia-reperfusion (I/R) injury.

Effects of low-dose methotrexate in spinal cord injury in rats.

BACKGROUND: This study was designed to evaluate the possible protective effects of low-dose methotrexate in the spinal cord injury (SCI) in rats. METHODS: Thirty-seven Wistar albino rats were used in the present study. Except for the animals of the Sham group, all animals were divided into two main groups, which were used in acute and subacute stage investigations. Then, thoracal laminectomy was performed, and except for the Sham group, SCI was induced using a temporary aneurysm clip. After clip compression, the experimental material (methotrexate or methylprednisolone) was administered intraperitoneally, except in the Sham and Control groups. Then, the spinal cords were removed to evaluate the SCI histopathologically and biochemically at the scheduled date. RESULTS: Neither experimental material was shown to reduce the histopathological grade in either stage of SCI. Low-dose methotrexate was shown to decrease lipid peroxidation levels only in the subacute stage of SCI. However, methylprednisolone and low-dose methotrexate could not decrease or block myeloperoxidase enzyme activation in either stage of SCI. CONCLUSION: Low-dose methotrexate was effective in reducing the lipid peroxidation levels in the subacute stage of SCI, although histopathological evaluation results and myeloperoxidase levels of all groups did not support this finding at either stage.

Inpatient evaluation of periodontal, esthetic and inflammatory parameters around dental implants and natural teeth.

AIM: The use of endosseous dental implants (DI) has become a successful treatment alternative. However, providing periimplant tissue health and achieving a natural esthetic look are important topics in this treatment. The aim of the present study was to evaluate periodontal and esthetic parameters around DI and natural teeth (NT) and also to analyze myeloperoxidase (MPO) levels in gingival crevicular fluid (GCF) and peri-implant sulcus fluid (PISF). MATERIALS AND METHODS: Twenty DI supported fixed prosthesis and contralateral 20 NT were enrolled to the present study. Clinical periodontal parameters (probing depth, clinical attachment level, gingival bleeding time index and gingival index) were recorded and GCF/PISF samples were obtained from mesial (mesiobuccal and mesiolingual) and distal (distobuccal and distolingual) sites of DI and NT. MPO levels were spectrophotometrically determined. Additionally clinical photographs were obtained and esthetical evaluations were performed by using Jemt papilla index. The parameters belong to DI and NT were compared and correlations were evaluated using statistical analysis. RESULTS: A total of 40 samples were evaluated. No statistically significant differences were detected between groups in all periodontal parameters and MPO levels from mesial and distal sites. Jemt papilla index scores were slightly higher in NT however, this difference was not statistically significant (p > 0.05). Total PES score were similiar in DI and NT groups. Significant correlations were detected between MPO and gingival index values as expected. CONCLUSION: These results suggest that DI and NT have similar inflammatory conditions and esthetics, representing DI as a predictable treatment option. CLINICAL SIGNIFICANCE: Dental implants are satisfactory treatments, they provide patient esthetic natural looking, phonetic and masticatory functions.

Effects of intracisternal and intravenous dexmedetomidine on ischemia-induced brain injury in rat: a comparative study.

AIM: To compare the effect of dexmedetomidine administered by intracisternal route with by intravenous route on brain tissue of rat after incomplete cerebral ischemia. MATERIAL AND METHODS: Cerebral ischemia was produced by the combination of right common carotid artery occlusion and hemorrhagic hypotension during 30 minutes. Thirty minutes before the ischemia, 0.1 ml 0.9% NaCl (Group SIC, n=6) or 9 µg/kg dexmedetomidine (Group DIC, n=6) was administered into the cisterna magna. For the intravenous groups, 9 µg/kg dexmedetomidine (Group DIV, n=6) or 0.9% NaCl (Group CONTROL, n=6) 5 ml/kg/h was given in 2 hours. After 24 hours, the lipid peroxidation levels were measured in the brain tissue and plasma. Hippocampal formations were used for histopathological examination. RESULTS: Intravenous dexmedetomidine produced a decrease in baseline mean arterial blood pressure and plasma glucose concentrations. There was a significant difference between the DIV group and DIC, SIC, CONTROL groups regarding the brain lipid peroxidation levels (p < 0.001, p < 0.001, p=0.001, respectively), and regarding the picnotic neuronal cell count (p < 0.001, p=0.01, p=0.009, respectively). Mean plasma lipid peroxidation levels of the DIV group was different from the DIC group (p=0.003). CONCLUSION: Systemically administered dexmedetomidine had neuroprotective effect in ischemia-induced neuronal damage, but centrally administered dexmedetomidine did not.

Evaluation of the neurotoxicity of the polyethylene glycol hydrogel dural sealant.

AIM: Although polyethylene glycol (PEG) is a neutral, biocompatible hydrophilic polymer recognized for its lack of interaction with biological barrier, its neurotoxicity has not been clearly identified in neurosurgery. This study is constructed to evaluate the possible neurotoxicity of a PEG hydrogel dural sealant. MATERIAL AND METHODS: After a burrhole was opened in the left parietal bone of the twenty five Wistar albino rats, the dura mater and cerebral cortex were incised and the experimental material (activated polyethylene glycol and polyethylene imine) was sprayed into the burrhole. Then brain tissues were harvested for histopathological and biochemical studies at 72 hours to investigate the acute stage changes and on 15th day to evaluate the chronic stage changes. RESULTS: There were statistically significant differences among the groups regarding the comparison of the values of the PMNL cell infiltration grades, gliosis and congestion in both acute and chronic stages. However, the values of the MNL cell infiltration grades, edema and fibrin formation, lipid peroxidation levels of harvested brain tissues were similar in all groups. CONCLUSION: Although this study did not present the detailed histopathological and biochemical evaluation results, it indicated that the application of the PEG-based hydrogel sealant was not associated with neurotoxicity, delayed healing, or degenerative changes.

Effects of intracisternal dexmedetomidine on cerebral neuronal cells in rat: a preliminary study.

AIM: The aim was to investigate whether dexmedetomidine had a toxic effect on cerebral neurons when it was administered centrally into the cerebrospinal fluid by the intracisternal route. MATERIAL AND METHODS: Eighteen rats were anesthetized and the right femoral artery was cannulated. Mean arterial pressures, heart rates, arterial carbon dioxide tension, arterial oxygen tension, and blood pH were recorded. When the free cerebrospinal fluid flow was seen, 0.1 ml normal saline (Group SIC, n=6) or 9 µg/kg diluted dexmedetomidine in 0.1 ml volume (Group DIC, n=6) was administered into the cisterna magna of rats. After 24 hours, the whole body blood was collected for measurement of plasma lipid peroxidation (LPO) levels. The hippocampal formations used for histopathological examination and measurement of tissue LPO levels. RESULTS: There was a statistically significant difference between the DIC/SIC groups and DIC/CONTROL groups regarding the brain LPO levels (p=0.002, p < 0.001, respectively). Plasma LPO levels were statistically different between the CONTROL/DIC groups, CONTROL/SIC groups, DIC/ SIC groups (p=0.002, p=0.047, p=0.025, respectively), The picnotic neuron counts were different between the CONTROL/SIC groups, CONTROL/ DIC groups, DIC/SIC groups (p < 0.001, p=0.001, p=0.024, respectively). CONCLUSION: In conclusion, dexmedetomidine had a toxic effect on cerebral neurons when it was administered centrally into the cerebrospinal fluid by the intracisternal route.

Effect of low-level laser therapy (LLLT) on orthodontic tooth movement.

The aim of this study is to evaluate the effects of low-level laser therapy (LLLT) on (1) the velocity of orthodontic tooth movement and (2) the nitric oxide levels in gingival crevicular fluid (GCF) during orthodontic treatment. The sample consisted of 20 patients (14 girls, six boys) whose maxillary first premolars were extracted and canines distalized. A gallium-aluminum-arsenide (Ga-Al-As) diode laser was applied on the day 0, and the 3rd, 7th, 14th, 21st, and 28th days when the retraction of the maxillary lateral incisors was initiated. The right maxillary lateral incisors composed the study group (the laser group), whereas the left maxillary lateral incisors served as the control. The teeth in the laser group received a total of ten doses of laser application: five doses from the buccal and five doses from the palatal side (two cervical, one middle, two apical) with an output power of 20 mW and a dose of 0.71 J /cm(2). Gingival crevicular fluid samples were obtained on the above-mentioned days, and the nitric oxide levels were analyzed. Bonferroni and repeated measures variant analysis tests were used for statistical analysis with the significance level set at p ≤ 0.05. The application of low-level laser therapy accelerated orthodontic tooth movement significantly; there were no statistically significant changes in the nitric oxide levels of the gingival crevicular fluid during orthodontic treatment.

The therapeutic effects of melatonin and nimodipine in rats after cerebral cortical injury.

AIM: Secondary brain injury starts after the initial traumatic impact and marked by an increase in the intracellular calcium concentrations.This cascadeeventually results in membrane lipid peroxidation and neuronal cell death. MATERIAL AND METHODS: We investigated the neuro-protective effects of nimodipine and melatonin in 38 rats after 6 hours of head trauma using the cortical impact injury model of Marmarou. RESULTS: Brain water in the melatonin-given group decreased significantly comparing to that of control group the brain water in the nimodipine given group increased significantly comparing to that of trauma group. Histopathologically, brain edema was significantly low in melatonin-administered group comparing to that of control group while there were no changes in brain edema in the nimodipine given group and in the group that both nimodipine and melatonin were administered in combination. MDA levels in the brain tissues were significantly lower in the melatonin and nimodipine groups comparing to those of trauma and control group however this difference was by far significant in melatonin group comparing to nimodipine group. CONCLUSION: Melatonin appears to have neuro-protective effects on the secondary brain damage while nimodipine and nimodipine plus melatonin combination did not show such neuro-protective effects on the secondary brain injury.

Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model.

PURPOSE: The aim of this study was to investigate the neuroprotective effects of propofol, thiopental, etomidate, and midazolam as anesthetic drugs in fetal rat brain in the ischemia-reperfusion (IR) model. METHODS: Pregnant rats of day 19 were randomly allocated into eight groups. Fetal brain ischemia was induced by clamping the utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by removing the clamps for 60 min. In the control group, fetal rat brains were obtained immediately after laparotomy. In the sham group, fetal rat brains were obtained 90 min after laparotomy. In the IR group, IR procedure was performed. No treatment was given in the IR group. One milliliter intralipid solution, 40 mg/kg propofol, 3 mg/kg thiopental, 0.1 mg/kg etomidate, and 3 mg/kg midazolam was administered intraperitoneally in the vehicle group, propofol group, thiopental group, etomidate group, and midazolam group, respectively, 20 min before IR procedure. At the end of the reperfusion period, the whole brains of the fetal rats were removed for evaluation of thiobarbituric acid reactive substances and for examination by electron microscopy. RESULTS: According to lipid peroxidation data, all the anesthetic drugs provide neuroprotection; however, ultrastructural findings and mitochondrial scoring confirms that only propofol and midazolam provides a strong neuroprotective effect. CONCLUSIONS: Propofol and midazolam may be used to protect fetal brain in case of acute fetal distress and hypoxic injury as a first choice anesthetic drug in cesarean delivery.

Neuroprotective effects of racemic ketamine and (S)-ketamine on spinal cord injury in rat.

BACKGROUND: The aim of this study was to investigate and to compare the potential neuroprotective effects of racemic ketamine, (S)-ketamine and methylprednisolone after an experimental spinal cord injury model in rats. METHODS: Fifty-nine Wistar albino rats were divided into three main groups as acute stage (A), subacute stage (SA) and sham groups and then acute and subacute stage groups were divided into four groups regarding the used drug as control (CONT), racemic ketamine (RK), (S)-ketamine (SK) and methylprednisolone (MP) groups. A dorsal laminectomy was performed; and spinal cord injury was induced by using a temporary aneurysm clip. Four hours later from the clip compression, except those of the sham and control groups, the drugs (60 mg/kg racemic ketamine, 60 mg/kg (S)-ketamine or 30 mg/kg methylprednisolone) were administered intraperitoneally. At 72th h and 7th days of the study, the spinal cords of rats were removed from T8 level to the conus medullaris level. The specimens were and evaluated histopathologically, tissue lipid peroxidation (LPO) and myeloperoxidation (MPO) levels were measured and biochemically. RESULTS: The histopathological results were similar both in the acute and in the subacute stage groups. There was a statistically significant difference among all groups regarding the tissue LPO levels (p<0.001). There was a statistically significant difference between the CONT-A group and the MP-A, RK-A and SK-A groups (p=0.004, p<0.001 and p=0.007, respectively) in acute stage and between the CONT-SA group and SK-SA group (p=0.002) in subacute stage. There was a statistically significant difference among all groups regarding the tissue MPO levels (p=0.001). The median MPO levels were similar among acute stage groups (p=0.057), but there was a statistical difference among subacute stage groups (p=0.046). CONCLUSION: (S)-ketamine is more effective than methylprednisolone and racemic ketamine to reduce the LPO levels in subacute stage of spinal cord injury in rats. And, it is as effective as methylprednisolone in preventing secondary spinal cord injury histopathologically.

Effect of curcumin on lipid peroxidation, early ultrastructural findings and neurological recovery after experimental spinal cord contusion injury in rats.

AIM: After acute spinal cord injury (SCI), a large number of axons are lost by a cascade of pathophysiological events known as a secondary injury. The main aim of the current study was to investigate the potential neuroprotective effects of curcumin on lipid peroxidation (LPO), neurological function, and ultrastructural findings after SCI. MATERIAL AND METHODS: Forty adult Wistar albino rats were randomized into five groups: control, SCI alone (50 g/cm weight drop), methylprednisolone sodium succinate (MPSS) (30 mg/kg), curcumin + dimethyl sulfoxide (DMSO) (300 mg/kg), and DMSO alone (0.1 mg/kg). RESULTS: Administration of curcumin significantly decreased LPO in first 24 hours. However, there were no differences in the neurological scores of injured rats between the medication groups and the control group. Curcumin was more effective than DMSO and MPSS in reducing LPO, whereas DMSO was more effective than curcumin and MPSS in minimizing ultrastuctural changes. The results of this study indicate that curcumin exerts a beneficial effect by decreasing LPO and may reduce tissue damage. CONCLUSION: Since ultrastructural and neurological findings does not support biochemical finding, our findings do not exclude the possibility that curcumin has a protective effect on the spinal cord ultrastructure and neurological recovery after SCI. A combination of curcumin with other vehicle may also have a considerable synergy in protecting spinal cord.

Methothrexate attenuates early neutrophil infiltration and the associated lipid peroxidation in the injured spinal cord but does not induce neurotoxicity in the uninjured spinal cord in rats.

BACKGROUND: The goal of most acute therapies for spinal cord injury (SCI) in humans include attenuation of the early inflammatory response and may limit the extent of tissue injury and the consequent disability. OBJECTIVE: The purpose of this study was to investigate the early effects of methothrexate (MTX) treatment on myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and ultrastructural findings in the injured and uninjured spinal cords of rats. The effects of MTX treatment were also compared with methylprednisolone sodium succinate (MPSS) treatment. METHODS: Wistar rats were divided into seven groups: control; trauma alone (50 g/cm weight drop trauma); SCI + MPSS (30 mg/kg); SCI + low-dose (0.5 mg/kg) MTX (LDMTX); SCI + higher-dose (1 mg/kg) MTX (HDMTX); non-trauma + LDMTX; non-trauma + HDMTX. RESULTS: Administration of MTX and MPSS treatments significantly decreased MPO activity (p < 0.05) and MDA level (p < 0.05) in the first 24 h. The MTX treatments, particularly HDMTX, were more effective than MPSS in reducing MPO activity, and MTX treatments were also more effective than MPSS in reducing MDA level (p < 0.05). The MTX treatment was more protective on large- and medium-diameter myelinated axons in minimizing ultrastructural changes in the spinal-cord-injured rats, but did not induce neurotoxicity in normal spinal cord. CONCLUSION: The results of this study indicate that MTX treatment has a beneficial effect by reducing early neutrophil infiltration and the associated lipid peroxidation, and has significantly protective effects on the injured spinal cord tissue in the first 24 h after SCI. Given the anti-inflammatory properties of MTX, a single dose of MTX a week is used for non-neoplastic disease in humans, and MTX may have a beneficial role in the immediate management of acute SCI.

Magnesium sulfate protects fetal skin from intrauterine ischemia reperfusion injury.

Intrauterine ischemia-reperfusion (I/R) injury in fetus occurs with multifactorial pathogenesis and results with multiorgan injury including skin. Magnesium has widespread use in obstetric practice. Inn addition to magnesium's tocolytic and neuroprotective properties, it also has free radical reducing effects. The aim of the present study was to demonstrate whether magnesium sulfate could have protective effect on fetal rat skin in intrauterine ischemia-reperfusion (I/R) injury. Fetal skin ischemia was induced by clamping the utero-ovarian arteries bilaterally for 30 min, and reperfusion was achieved by removing the clamps for 60 min in 19-day pregnant rats. Magnesium Sulfate (MgSO(4)) was given to pregnant rats 20 min before I/R injury at the dose of 600 mg/kg in magnesium treatment group. No ischemia reperfusion was applied to control and sham-operated groups. Lipid peroxidation from the skin tissues was determined as thiobarbituric acid reactive substances (TBARS). Myeloperoxidase (MPO) activity was determined for neutrophil activation. The results showed that the levels of TBARS and MPO increased significantly in the fetal rat skin after I/R injury compared to control group. Levels of TBARS and MPO were significantly lower than those of I/R group in Magnesium-treated group. In conclusion, intrauterine ischemia-reperfusion may produce considerable fetal skin injury. Increased TBARS and MPO activity can be inhibited by magnesium treatment. This suggests that magnesium treatment may have protective effect on fetal rat skin in intrauterine I/R injury.