Zeolitic imidazolate framework-90 loaded with methylprednisolone sodium succinate effectively reduces hypertrophic scar in vivo.

Hypertrophic scar (HS) is characterized by an abnormal fibroblast-myofibroblast transformation; non-apoptosis of fibroblasts; and redundant expression of TGF-ß1, VEGF, α-SMA, and collagen I/III. An HS affects patients' physical and psychological quality of life, leading to joint dysfunction and skin cancer. However, there is currently no satisfactory drug to treat this disorder. In this study, we constructed methylprednisolone sodium succinate (MPSS) encapsulated ZIF-90 (MPSS@ZIF-90) for the effective treatment of an HS. The encapsulation of MPSS in ZIF-90 can achieve the controllable drug release of MPSS and prolong its effective treatment time. MPSS@ZIF-90 enhanced the apoptosis of human hypertrophic scar fibroblasts and downregulated the overexpression of TGF-ß1, VEGF, α-SMA, and collagen I/III both in vitro and in vivo. The instant injection of MPSS@ZIF-90 effectively intervened with the formation of the HS after 28 days. On the contrary, MPSS@ZIF-90 greatly reduced the HS with two injections and 14 days of treatment after the HS was formed. This work provides evidence of effective intervention in the formation of an HS and the therapeutic effectiveness of MPSS@ZIF-90 with short treatment periods in vivo. It suggests that MPSS@ZIF-90 can be used as a biomedical option in the treatment of skin wounds and may reveal the potential molecular basis for promising future antifibrotic agents against scarring.

Microneedle/CD-MOF-mediated transdural controlled release of methylprednisolone sodium succinate after spinal cord injury.

A new method of transdural delivering drugs to the spinal cord has been developed, involving the use of microneedles (MNs) and a ß-cyclodextrin metal-organic framework (CD-MOF). This epidural microneedle array, dubbed MNs@CD-MOF@MPSS, can be utilized to deliver methylprednisolone sodium succinate (MPSS) to the site of spinal cord injury (SCI) in a controlled manner. MNs allows to generate micropores in the dura for direct drug delivery to the spinal cord, overcoming tissue barriers and targeting damaged regions. Additionally, the CD-MOF provides a secondary extended release after separating from the MNs. In in vitro study, inward MNs increased cellular absorption of MPSS and then reduced LPS-induced M1 polarization of microglia. And animal studies have shown that this method of drug delivery results in improved BMS scores and a reduction in M1 phenotype microphage and glial scar formation. Furthermore, the downregulation of the NLRP3-positive inflammasome and related pro-inflammatory cytokines was observed. In conclusion, this new drug platform has potential for clinical application in spinal cord diseases and is a valuable composite for minimally transdural controlled drug delivery. STATEMENT OF SIGNIFICANCE: This research presents a new epidural microneedle patch made up of microneedles (MNs) and a ß-cyclodextrin metal-organic framework (CD-MOF). The epidural microneedle patch boasts high drug loading capacity, the ability to penetrate the dura, and controlled release. When loaded with methylprednisolone sodium succinate (MPSS), it effectively reduces inflammation and improves neurological function after spinal cord injury. Therefore, it is a novel and promising drug platform for the treatment of spinal cord diseases in a clinical setting.

Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy.

A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy.

The role of low level laser therapy on neuropathic pain relief and interleukin-6 expression following spinal cord injury: An experimental study.

INTRODUCTION: The effect of Low Level Laser Therapy (LLLT) as a non-invasive treatment of spinal cord injury (SCI) is still under investigation. Therefore, the present study aimed to evaluate the effectiveness of LLLT on neuropathic pain and interleukin-6 (IL-6) expression following SCI in male rats. METHODS: 46 adult male rats were divided into 5 groups of control, SCI, treatment with methylprednisolone sodium succinate (MPSS), 1-week LLLT and 2-week LLLT. Animals underwent behavioral evaluations for motor behavior, level of allodynia and hyperalgesia every week. At the end, spinal cord was extracted and IL-6 level was assessed by ELISA method. RESULTS: Treatment with MPSS and 2-week LLLT had led to motor function recovery (df: 24, 145; F=223.5; p <0.001). SCI did not affect mechanical (df: 24, 145; F=0.5; p=0.09), and cold allodynia (df: 24, 145; F=0.3; p=0.17) but significantly increased mechanical (df: 24, 145; F=21.4; p<0.001) and heat hyperalgesia (df: 24, 145; F=16.1; p<0.001). Treatment with MPSS and 1 and 2-weeks LLLT improved mechanical hyperalgesia (p<0.05) and heat hyperalgesia (p<0.01). The increased level of IL-6 following SCI was also compensated by administration of MPSS or LLLT (df: 4, 10; F=8.74; p=0.003). CONCLUSION: Findings show that long periods of LLLT have better effects in improving the complication of SCI. In summation, since LLLT does not cause the side effects of MPSS, long-term use of LLLT may be a proper alternative for MPSS in decreasing post SCI side effects.

Effects of erythropoietin and methylprednisolone on AQP4 expression in astrocytes.

Methylprednisolone sodium succinate (MPSS) has been suggested as a treatment for spinal cord injury (SCI), but its use has been limited due to its adverse effects. Erythropoietin (EPO) has been suggested as a promising candidate for limiting SCI in mammals. The aim of the present study was to investigate the effects of EPO in combination with MPSS on astrocytes following ischemic injury in vitro. Astrocytes were isolated from the cerebral cortex of postnatal day 3 Sprague­Dawley rats and cultured in vitro. Astrocyte ischemic injury was induced by oxygen and glucose deprivation for 4 h, and reperfusion was simulated by subsequent culture under normoxic conditions. The effects of EPO and MPSS on the expression of aquaporin­4 (AQP4) were investigated. Ischemic astrocytes were treated with EPO (10 U/ml), MPSS (10 µg/ml), or EPO (10 U/ml) in combination with MPSS (10 µg/ml) during reperfusion. The cell viability of astrocytes was assessed using an MTT assay. The mRNA and protein expression levels of AQP4 were determined using reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. The role of the protein kinase C (PKC) signaling pathway in the molecular mechanisms underlying the effects of EPO and MPSS was also investigated. The present results demonstrated that following treatment with EPO and MPSS, the mRNA expression levels of AQP4 were upregulated and cell viability was enhanced. EPO and MPSS effectively inhibited the oxygen and glucose deprivation­mediated downregulation of AQP4 following reperfusion. In addition, the combined treatment with EPO and MPSS exhibited higher AQP4 expression levels and cell viability compared with each treatment alone. Finally, the effects of EPO and MPSS on AQP4 expression were partially reversed by pretreatment with the PKC inhibitor Ro 31­8220. The present study indicated that EPO and MPSS had a synergistic effect on AQP4 expression following reperfusion, and suggest that they may be combined in the treatment of SCI.

Acute Hypotonia in an Infant.

BACKGROUND: Acute flaccid myelitis (AFM) is increasing in incidence in the United States and presenting to emergency departments (EDs) across the country. This clinical entity presents as acute paralysis, with magnetic resonance imaging changes in the gray matter only in children younger than 21 years of age. The etiology is unknown, although preceding viral illnesses are common. There are no consensus guidelines regarding treatment. CASE REPORT: A 4-month-old girl presented with decreased bilateral arm movement. The history consisted of a recent upper respiratory illness and abrupt decline in movement. She was found to have truncal and peripheral hypotonia, while maintaining her airway. Magnetic resonance imaging found gray matter hyperintensity at C2-C6, with no white matter changes. The patient was positive for enterovirus. Intravenous steroids and intravenous immunoglobulin were given, with slight improvement prior to discharge to an inpatient rehabilitation center. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: AFM was largely nonexistent in the United States after implementation of the polio vaccine, but the incidence has recently increased. Pediatric patients are now presenting to EDs with acute hypotonia, and emergency physicians must recognize how to differentiate this emerging diagnosis from other causes of acute flaccid paralysis. The clinical course of AFM does not seem to change acutely, in stark contrast to disease entities like botulism, which can change in hours. Patients with AFM do not need aggressive ED diagnostic evaluation, but rather transfer to a pediatric hospital for further care. Therefore, discerning the etiology of pediatric hypotonia with history and physical examination alone is important.

Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage.

Inflammation and disruption of the blood-brain barrier (BBB) cause oedema and secondary brain injury after intracranial haemorrhage (ICH), which is closely related to patient prognosis. Methylprednisolone sodium succinate (MPSS), a well-known immunosuppressive agent, is widely applied in many diseases to inhibit inflammation. In this study, we investigated the effect of MPSS on inflammation and disruption of the BBB in a model mouse of ICH. ICH was induced by injecting collagenase into the right striatum of male C57/BL mice. Permeability of BBB was measured with Evans Blue assay and brain oedema was detected by measurement of brain water content. Expressions of NF-κB, TLR4, occludin, ZO-1, IL-1ß, TNF-α, Bax, and Bcl-2 were determined by Western Blot. Neutrophils, microglia were measured by immunohistochemistry staining, neuronal apoptosis was measured by TUNEL and NeuN co-stained. Administration of MPSS post-ICH significantly reduced permeability of the BBB and brain oedema and upregulated expression of ZO-1 and Occludin. MPSS inhibited inflammatory responses, including reducing proinflammatory cytokines (IL-1ß, TNF-α), suppressing infiltration of neutrophils and activation of microglia. This was accompanied by attenuated activation of the TLR4/NF-κB signalling pathway. In addition, MPSS reduced neuronal apoptosis through increasing Bcl-2 expression and reducing Bax expression. MPSS suppressed inflammatory responses, attenuated disruption of the BBB and reduced neuronal apoptosis, contributing to reduction of secondary brain injury after ICH. These results suggest that MPSS may be a potential therapy for ICH.

Methylprednisolone sodium succinate reduces spinal cord swelling but does not affect recovery of dogs with surgically treated thoracolumbar intervertebral disk herniation.

The effect of methylprednisolone sodium succinate (MPSS) therapy was studied in 50 dogs with surgically treated Hansen type I thoracolumbar intervertebral disk herniation (TL-IVDH). Administration of MPSS significantly reduced the swelling of the spinal cord. The sensitivity of localization of disk extrusion using myelography in the MPSS group was 92.3%, and in the non-administration group was 83.3%. No significant difference in recovery rate or length of recovery time was found between the two groups. Administration of MPSS reduced spinal cord swelling, but has no effect on recovery in dogs after surgery for TL-IVDH.

The effects of diet and corticosteroid-induced immune suppression during infection by Haemonchus contortus in lambs.

To evaluate the effects of Diet and corticosteroid-induced immune suppression during infection by Haemonchus contortus, 28 lambs were allocated to one of four groups treated as follows: Group Basal Diet - Normal; Group Basal Diet - Immune-Suppressed; Group Supplemented Diet - Normal; and Group Supplemented Diet - Immune-Suppressed. The Basal Diet contained Cynodon dactylon (cv. coast cross) hay with 82 g crude protein (CP)/kg dry matter (DM), which was provided to the lambs in all groups ad libitum. In addition, animals on the Supplemented Diet received daily a commercial concentrate containing 171 g CP/kg DM, which was offered in an amount corresponding to 3% of the animal's live weight. The Immune-Suppressed groups received treatments with the glucocorticoid methylprednisolone sodium succinate (1.33 mg/kg of body weight), administered weekly. All lambs received a single infection with 4000 H. contortus infective larvae (L3) and were euthanised 28 days post-infection. Differences in pH and in the short-chain fatty acid (SCFA) concentrations occurred in rumen as a result of the distinct Diets offered to lambs. Such changes, however, did not have any apparent effect on larvae exsheathment and/or larvae survival inside the rumen, with all groups presenting similar worm burdens. However, animals on the Supplemented Diet presented reductions in worm growth and faecal egg counts. There was a significant effect of the Diet on the IgG levels against total antigens of H. contortus L3 from 7 to 27 days post-infection, with supplemented animals showing higher overall mean values (P<0.05). The immunosuppressive treatments had no effect on worm burden despite the reduction in the numbers of inflammatory cells in the abomasal mucosa of the Immune-Suppressed groups. These groups showed longer worms and females with more eggs in comparison with their counterparts fed each Diet; however, only the length of males was significantly affected (P<0.05). In conclusion, the changes caused in the rumen contents by supplementation with concentrate did not impair H. contortus establishment.

Use of Mometasone furoate in prolonged treatment of experimental spinal cord injury in mice: A comparative study of three different glucocorticoids.

Traumatic spinal cord injury (SCI) represents one of the most disabling injuries of the human body causing temporary or permanent sensory and/or motor system deficit, particularly hind limb locomotor function impairment. At present, steroidal inflammatory drugs, in particular methylprednisolone sodium succinate (MPSS) are the first line choice treatment of acute SCI. Despite progress in pharmacological, surgical and rehabilitative treatment approaches, SCI still remains a very complex medical and psychological challenge, with no curative therapy available. The aim of the present study was to compare the efficacy of MPSS in respect to other GCs such as dexamethasone (Dex) and mometasone furoate (MF) in an in vitro suitable model of LPS-induced inflammation in J774 cells as well as in an in vivo experimental mouse SCI (compression model). In both the in vitro and in vivo experiments, MF resulted surprisingly more potent than Dex and MPSS. In detail, mice sacrificed seven days after induction of SCI trauma resulted not only in tissue damage, cellular infiltration, fibrosis, astrocyte activation, iNOS expression, extracellular signal regulated kinase 1/2 phosphorylation in injured tissue, poly (ADP-ribose) polymerase 1 (PARP-1) activation but also apoptosis (Bax and Bcl-2 expression). All three GCs demonstrated the ability to modulate inflammatory, oxidative as well as apoptotic pathways, but MF demonstrated the best efficacy, while Dex and MPSS showed alternative potency with a different degree of protection. Therefore, we can conclude that MF is the best candidate for post-traumatic chronic treatment, since it ameliorates different molecular pathways involved in the damage's propagation to the surrounding areas of the injured spinal cord.

Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases.

The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs' unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a "water-soluble" amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of ß-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug's therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component.

Local application of corticosteroids combined with surgery for the treatment of chronic subdural hematoma.

AIM: Combination treatment consisting of surgery and pre-or post-operative corticosteroids for chronic subdural hematoma (CSH) tend to have better outcomes than surgery only. However, there are many complications after long-term use of corticosteroids. In this study, we evaluated the clinical outcomes of local application of corticosteroids combined with surgery for CSH. MATERIAL AND METHODS: We retrospectively analysed the data of the patients undergoing surgery and local application of Methylprednisolone Sodium Succinate for Injection (MPSS) into the hematoma cavity. Neurological status was assessed by Markwalder's Grading Scale (MGS). Recurrence was defined as deteriorating neurological status with radiological evidence of reaccumulation. RESULTS: A total of 26 patients were enrolled in this study. During the follow-up period, all patients made excellent neurological recovery. 24 (92.3%) patients' MGS was grade 0 at 12 months after the surgery. There was no mortality or recurrence. 5 patients (19.2%) suffered postoperative complications, of which 2 developed some subdural air collection, 2 had a partial seizure attack and 1 developed an acute epidural hemorrhage. CONCLUSION: The results suggest that local application of MPSS combined with surgery is a safe and effective method in the management of CSH. It may reduce hematoma recurrence.

Effects of Therapeutic Hypothermia on Apoptosis and Autophagy After Spinal Cord Injury in Rats.

STUDY DESIGN: Animal study. OBJECTIVE: To further investigate the effects of therapeutic hypothermia (TH), the present study compared autophagy and apoptosis after treatment with either therapeutic moderate systemic hypothermia or methylprednisolone sodium succinate (MP) in a rat model of acute spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: The neuroprotective effects of TH have recently become an important topic in the field of SCI research. METHODS: All rats were subjected to a 25-g/cm spinal cord contusion over the ninth thoracic vertebrae. After the induction of SCI, the control group did not receive any further treatment, TH group immediately received moderate systemic hypothermia for 4 hours, and MP group was administered high-dose MP. The rats were killed either 2 or 7 days after SCI, and the injured spinal cord tissues were obtained. Apoptosis and autophagy were assessed by immunohistochemical analyses and Western blot analyses. In addition, the microarchitecture of the autophagosomes was evaluated using transmission electron microscopy, and the motor activity of the rats was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale. RESULTS: Compared with controls, there was a significant reduction in the expression levels of cleaved caspase-8, -9, and -3 in the TH- and MP-treated groups 2 days after SCI. Moreover, compared with the control group, the expression of LC3II and Beclin-1 exhibited a significant decrease on day 2 after treatment with TH. The numbers of transferase dUTP nicked-end labeling and LC3-positive cells were significantly lower on days 2 and 7. The Basso-Beattie-Bresnahan ratings were significantly higher 6 weeks after SCI in both the TH- and MP-treated groups than in the control group. CONCLUSION: Both TH and MP have neuroprotective effects on injured spinal cord tissues via the inhibition of apoptosis and autophagy. Thus, the application of moderate systemic hypothermia may be a useful treatment modality after acute SCI. LEVEL OF EVIDENCE: N/A.

The dose-dependent neuroprotective effect of alpha-lipoic acid in experimental spinal cord injury.

BACKGROUND AND PURPOSE: Free radical production after spinal cord injury (SCI) plays an important role in secondary damage. The aim of this study was to investigate neuroprotective effects of the powerful antioxidant alpha-lipoic acid (ALA) in a spinal cord clip compression injury model. MATERIAL AND METHODS: Fifty-six Sprague-Dawley rats, weighing between 210 and 300 g, were randomly divided into seven groups. Spinal cord injury was performed by an aneurysm clip placed extradurally at the level of T9. Group 1 (sham) received laminectomy only. Group 2 (control) received SCI; Group 3 received 30 mg/kg of methylprednisolone sodium succinate (MPSS); Groups 4, 5, 6 and 7 received ALA at doses of 50, 100, 150, 200 mg/kg, respectively, via the intraperitoneal route immediately after SCI. The rats were neurologically tested 24 hours after trauma. Spinal cord samples from injury sites were harvested for measurement of lipid peroxidation products and histopathological evaluation. RESULTS: Spinal cord malonyldialdehyde levels of rats in treatment groups decreased after administration of ALA. The difference between the trauma group and groups receiving MPSS-ALA was statistically significant. The difference between the ALA (50, 100, 150 mg/kg) and MPSS groups was insignificant. Group 7 (ALA 200 mg/kg) was excluded from the study because of the possible toxic effect. Alpha lipoic acid and MPSS had similar effects on spinal cord injury in terms of lipid peroxidation, neurological recovery and histopathological changes. CONCLUSIONS: Alpha lipoic acid at a dose range of 50-150 mg/ kg is as effective as MPSS (30 mg/kg) in neuroprotection after SCI. Further, more detailed experimental studies are needed to determine the effects of ALA on the detrimental results of secondary SCI before its use in humans.

The alterations of matrix metalloproteinase-9 in mouse brainstem during herpes simplex virus type 1-induced facial palsy.

The aim of this study is to explore the changes of matrix metalloproteinase-9 (MMP9) in the mouse brainstem during the development of facial paralysis induced by herpes simplex virus type 1 (HSV-1) and the inhibitory effect of methylprednisolone sodium succinate (MPSS) on MMP9 expression. HSV-1 was inoculated into the surface of posterior auricle of mouse to establish a paralyzed animal model. The paralyzed mice were divided randomly into three groups. In one group without any treatment, mice were killed at different time points of 6 h, 1, 2, 3, and 7 days post-induction of facial paralysis; in the other two groups, mice were injected daily with MPSS and a combination of MPSS and glucocorticoid receptor blocker (RU486) for 2 days, respectively. The expression of MMP9 in the facial nucleus of brainstem was detected by Western blot, quantitative real-time polymerase chain reaction, and immunofluorescence technique. A total of 52.07 % of mice developed unilateral facial paralysis after inoculated with HSV-1. Both mRNA and protein expression of MMP9 were present at low levels in normal facial nucleus of brainstem and were increased significantly after facial paralysis with its peak time at 2 days post-induction of facial paralysis. Expression of MMP9 of paralyzed mice was inhibited by MPSS, and the inhibition could be blocked by RU486. Our findings suggest that MMP9 in mouse brainstem is involved in the evolution of facial palsy induced by HSV-1 and may play an important role in the pathogenesis of this disease. MPSS might effectively relieve HSV-1-mediated damages by inhibitory effect on expression of MMP9 in HSV-1-induced facial paralysis.

Quercetin prevents experimental glucocorticoid-induced osteoporosis: a comparative study with alendronate.

Glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. The aim of this study was to compare the efficacy of quercetin, a plant-derived flavonoid, with alendronate in the prevention of GIO. Fifty-six Sprague-Dawley rats were randomly distributed among 7 groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg methylprednisolone sodium succinate (MP)/kg body mass; (iii) MP + 40 µg alendronate/kg; (iv) MP + 50 mg quercetin/kg; (v) MP + 40 µg alendronate/kg + 50 mg quercetin/kg; (vi) MP + 150 mg quercetin/kg; and (vii) MP + 40 µg alendronate/kg + 150 mg quercetin/kg. MP and alendronate were injected subcutaneously and quercetin was administered by oral gavage 3 days a week. At the end of the study, femur breaking strength was significantly decreased as a consequence of MP injection. This decrease was completely compensated for in groups receiving 50 mg quercetin/kg plus alendronate, and 150 mg quercetin/kg with or without alendronate. Quercetin noticeably elevated osteocalcin as a bone formation marker, while alendronate did not show such an effect. In addition, administration of 150 mg quercetin/kg increased femoral trabecular and cortical thickness by 36% and 22%, respectively, compared with the MP-treated group. These data suggest that 150 mg quercetin/kg, alone or in combination with alendronate, can completely prevent GIO through its bone formation stimulatory effect.

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.

Lack of protective effect of local administration of triamcinolone or systemic treatment with methylprednisolone against damages caused by optic nerve crush in rats.

The purpose of the present study was to investigate the effects of administrations of triamcinolone acetonide and systemic methylprednisolone sodium succinate on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of optic nerve crush. The treated groups either received triamcinolone immediately in the form of two pieces of soaked-gelform surrounding retrobulbar optic nerves (0.5 mg/per gelform) or methylprednisolone via peritoneal injection, and control group received intra-peritoneal injection with phosphate-buffered saline (PBS) after crush experiments. RGC density was counted by retrograde labeling with Fluorogold, and visual function was assessed by flash visual-evoked potentials. Terminal transferase dUTP nick end-labeling (TUNEL) assays, Western blot analysis of serine/threonine kinase (p-Akt), extracellular signal-regulated kinases (p-ERK) and signal transducer and activator of transcription 3 (p-STAT3) and immunohistochemistry of ED1, marker of macrophage/microglia in the optic nerve were conducted. Two and four weeks after optic nerve crush experiments, neither triamcinolone nor methylprednisolone treatment rescued the RGC from death in the central and mid-peripheral retinas compared with those of the corresponding optic nerve-crushed and PBS-treated rats. Visual-evoked potentials measurements showed a prolonged latency of the P(1) wave in all treated groups (triamcinolone-treated: 123 ± 23 ms, methylprednisolone-treated: 133 ± 25 ms and PBS-treated: 151 ± 55 ms) after two weeks. TUNEL assays showed that there was no decrease in apoptotic cells in the RGC layers of both triamcinolone treated and methylprednisolone-treated retinas. Western blot analysis showed that p-AKT, p-ERK and p-Stat3 were not up-regulated in either retina of the triamcinolone or methylprednisolone treated rats. In addition, the number of ED1-positive cells was not attenuated at the lesion sites of the ON in either treatment group. Based upon these results, we conclude that neither retrobulbar administration of triamcinolone nor systemic administration of methylprednisolone has any neuroprotective effects in a rat model of optic nerve crush.

Effects of systemic administration of methylprednisolone on residual hearing in an animal model of cochlear implantation.

CONCLUSION: Delivery of intramuscular injection of methylprednisolone around the implantation surgery improved the hearing threshold shift induced by cochlear implantation. OBJECTIVES: During electroacoustic cochlear implantation surgery, the residual hearing is not preserved in about 15% of cases. In this study, we tested the effects of intramuscular administration of methylprednisolone on the hearing loss induced by cochlear implantation in a model of guinea pig cochlear implantation. METHODS: Eleven guinea pigs with normal hearing were implanted with a 254 µm diameter silicone array through a cochleostomy, and the effects on hearing of longstanding array insertion (21 days) were assessed. Six of the implanted animals received intramuscular administration of methylprednisolone. Auditory brainstem response recordings were performed before and up to 21 days after the cochlear implantation. CT scans were performed in some animals 1 month after implantation. RESULTS: CT scans confirmed that the array was well positioned in tested animals. From days 3 to 21, a hearing loss of about 30 dB on all frequencies was observed in the implanted nontreated group. This hearing loss remained stable during the whole follow-up period. Compared with implanted nontreated animals, the hearing threshold shift decreased by 12 dB in animals treated with methylprednisolone.

Effect of granulocyte-colony stimulating factor on spinal cord tissue after experimental contusion injury.

The purpose of this study was to investigate the early effects of granulocyte-colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury (SCI). We also compared the effects of G-CSF and methylprednisolone sodium succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 µg/kg). Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of this study indicate that G-CSF exerts a beneficial effect by decreasing MPO activity and LPO and may reduce tissue damage in the first 24 hours after SCI. Our findings do not exclude the possibility that G-CSF has a protective effect on spinal cord ultrastructure after the first 24 hours following SCI.