miRNA contributes to neuropathic pains.

Neuropathic pain (NP) is a kind of chronic pain caused by direct injury to the peripheral or central nervous system (CNS). microRNAs (miRNAs) are small noncoding RNAs that mostly interact with the 3 untranslated region of messenger RNAs (mRNAs) to regulate the expression of multiple genes. NP is characterized by changes in the expression of receptors and mediators, and there is evidence that miRNAs may contribute to some of these alterations. In this review, we aimed to fully comprehend the connection between NP and miRNA; and also, to establish a link between neurology, biology, and dentistry. Studies have shown that targeting miRNAs may be an effective therapeutic strategy for the treatment of chronic pain and potential target for the prevention of NP.

The Role of Resveratrol in Aging and Senescence: A Focus on Molecular Mechanisms.

Resveratrol (Res), a polyphenol found in red wine, has been shown to decelerate aging, the progressive loss of physiological integrity and cellular senescence, characterized by the inability to progress through the cell cycle. No successful clinical trials have yet to be completed in humans on dose limitations. Yet, the potent anti-aging and anti-senescence efficacy of Res has been documented in several in vivo animal models. In this review, we highlight the molecular mechanisms of Res efficacy in anti-aging disorders, such as diabetes, neurodegenerative disorders, eye diseases, and cardiovascular diseases.

Effects of Intraventricular Vancomycin Administration on the Prevention of Ventricular Shunt Infection.

INTRODUCTION AND OBJECTIVES: Shunt infection causes death in many patients diagnosed with hydrocephalus and increases the duration of hospitalization and treatment costs. A high percentage of children are forced to undergo re-surgery due to shunt dysfunction or infection. The present study aimed to investigate the role of intraventricular (IVT) vancomycin in the prevention of ventricular shunt infection in children with hydrocephalus who were referred to Akbar Hospital in Mashhad, Iran, between the years 2017 and 2021. MATERIALS AND METHODS: The present descriptive cross-sectional study was conducted on 192 children with hydrocephalus who underwent shunt surgery at Akbar Hospital in Mashhad, Iran, between the years 2017 and 2021. Patients were divided into two groups of intervention (n=69) and control (n=123). The patients in the intervention group received 30 mg of IVT vancomycin during shunt surgery. The rate of shunt obstruction and infection were then compared between the two study groups. RESULTS: The two study groups were matched in terms of demographic and clinical information except for gender (P=0.02). Moreover, no significant difference was reported between the two groups in terms of intelligence development (χ2=0.51; P=0.47), verbal development (χ2=0.1; P=0.75), and movement development (χ2=1.05; P=0.3). The frequency of shunt infection and shunt obstruction was estimated at 8.8% and 18.2%, respectively. The shunt infection rate was lower in the vancomycin IVT group than in the control group (χ2=4.07; P=0.04), while no difference was observed between the two groups in terms of shunt obstruction (χ2=3.66; P=0.056). The comparison of the two study groups indicated no significant difference between them in terms of mortality (χ2=0.004; P=0.95). CONCLUSION: It seems that IVT vancomycin should be recommended for inclusion in hydrocephalus surgery protocol to reduce postoperative shunt infection. It is recommended that shunt protocols be adopted in future multicenter prospective randomized controlled trials on the reduction of ventriculoperitoneal shunt infections to further evaluate the efficacy of IVT antibiotics.

Parietal bone osteoid osteoma: A rare cause of button sequestrum sign in pediatrics. Case report and review of literature.

The current study evaluates a rare case of parietal bone osteoid osteoma in pediatrics and review the differential diagnosis of button sequestrum sign in the literature. A 12-year-old girl expressed localized pain in the right parietal bone. MRI represented enhancing nodule with button sequestrum sign appearance.

Effects of exposure in utero to buprenorphine on oxidative stress and apoptosis in the hippocampus of rat pups.

The study investigated the effect of buprenorphine (BUP) on oxidative indices and gene expression of apoptotic molecules in the hippocampus of neonates during the fetal stage. BUP (1 or 0.5 mg/kg) was subcutaneously administrated to pregnant rat dams. After parturition, the pups were maintained to the end of breastfeeding period, then hippocampi were assessed for oxidative stress indices [glutathione (GSH), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total antioxidant capacity (TAC)] and mRNA expression of apoptotic markers (Bax, Bcl2 and caspase 3). Our data indicated that BUP (0.5 mg/kg) administration during gestation significantly increased GSH and TAC concentrations in the hippocampus of pups versus control group (p < 0.05). BUP (0.5 and 1 mg/kg) administration significantly elevated the expression levels of Bcl2 in the hippocampus of neonates compared with controls. BUP injection (0.5 and 1 mg/kg) to pregnant rats markedly reduced the expression levels of caspase 3 in the hippocampus of neonates in BUP 0.5 group (p < 0.01) and BUP 1 group (p < 0.05) versus the controls. Our study indicated that BUP may potentiate antioxidant system and inhibit apoptosis and oxidative stress in the hippocampus of neonates received this drug during the fetal stage.

Curcumin Efficacy in a Serum/Glucose Deprivation-Induced Neuronal PC12 Injury Model.

BACKGROUND: Glucose/serum deprivation (GSD), has been used for understanding molecular mechanisms of neuronal damage during ischemia. It has been suggested that curcumin may improve neurodegenerative diseases. AIM: In this study, the protective effects of curcumin and its underlying mechanisms were investigated in PC12 cells upon GSD-induced stress. METHODS: PC12 cells were cultured in DMEM overnight and then incubated in GSD condition for either 6 or 12h. GSD-treated cells were pretreated with various concentrations of curcumin (10, 20, and 40 µM) for 5h. The cell viability, apoptosis, reactive oxygen species (ROS) level, oxidative stress, expression of apoptosis-related genes, and IL-6 were determined. RESULTS: Curcumin increased cell viability and caused an anti-apoptotic effect in PC12 cells exposed for 12h to GSD . Curcumin also increased antioxidant enzyme expression, suppressed lipid peroxidation, and decreased interleukin-6 secretion in PC12 cells subjected to GSD. In addition, pretreatment with curcumin down-regulated pro-apoptotic (Bax), and up-regulated antiapoptotic (Bcl2) mediators. CONCLUSION: Curcumin mitigates many of the adverse effects of ischemia, and therefore, should be considered as an adjunct therapy in ischemic patients.

National Guidelines for Cognitive Assessment and Rehabilitation of Iranian Traumatic Brain Injury Patients.

BACKGROUND: Individuals with moderate to severe traumatic brain injury (TBI) often have prolonged cognitive impairments, resulting in long-term problems with their real-life activities. Given the urgent need for evidence-based recommendations for neuropsychological management of Iranian TBI patients, the current work aimed to adapt eligible international guidelines for cognitive assessment and rehabilitation of the TBI patients in Iran. METHODS: The project was led by an executive committee, under the supervision of the Iranian Ministry of Health and Medical Education (MOHME). Following a systematic literature search and selection process, four guidelines were included for adaptation. Clinical recommendations of the source guidelines were tabulated as possible clinical scenarios for 90 PICO clinical questions covering all relevant phases of care. After summing up the scenarios, our initial list of recommendations was drafted according to the Iranian patients' conditions. The final decision-making, with the contribution of a national interdisciplinary panel of 37 experts from across the country, was conducted in two rounds using online and offline survey forms (Round 1), and face-to-face and telephone meetings (Round 2). RESULTS: A total of 63 recommendations in six sections were included in the final list of recommendations, among which 24 were considered as key recommendations. In addition, some of the recommendations were identified as fundamental, meaning that proper implementation of the other recommendations is largely dependent on their implementation. CONCLUSION: Iranian health policy makers and rehabilitation program managers are recommended to address some fundamental issues to provide the necessary infrastructure to set up an efficient cognitive rehabilitation service system.

Impact of Cannabis-Based Medicine on Alzheimer's Disease by Focusing on the Amyloid ß-Modifications: A Systematic Study.

Deposition of Amyloid-beta (Aß) peptide in the brain is the leading source of the onset and progression of Alzheimer's Disease (AD). Recent studies have suggested that anti-amyloidogenic agents may be a suitable therapeutic strategy for AD. The current review was proposed to address the beneficial effects of cannabis-based drugs for the treatment of AD, focusing primarily on Aß modifications. Keywords related to AD, Aß, and cannabis-based on MeSH were identified and were searched in PubMed, Google Scholar, Scopus, Ovid-Medline, and Web of Science from inception until 15 March 2020. The full text of identified papers was obtained and assessed based on exclusion and inclusion criteria. The review is based on articles that have focused on AD and the amyloidogenic pathway. A total of 17 studies were identified based on the inclusion criteria; however, nine studies qualified for this systematic review. The maximum and minimum cannabis dosages, mostly CBD and THC in animal studies, were 0.75 and 50 mg/kg, respectively. Cannabis (CBD and THC) was injected for 10 to 21 days. The findings of the 9 articles indicated that cannabis-based drugs might modulate Aß modifications in several AD models. Our findings establish that cannabis-based drugs inhibited the progression of AD by modulating Aß modifications.

Curcumin Loaded in Niosomal Nanoparticles Improved the Anti-tumor Effects of Free Curcumin on Glioblastoma Stem-like Cells: an In Vitro Study.

Using a novel curcumin-loaded niosome nanoparticle (CM-NP), the present study was designed to evaluate the effect of curcumin on human glioblastoma stem-like cells (GSCs). CM-NP has a diameter of ~ 60 nm and a zeta potential of ~ - 35 mV with a constant physicochemical stability. The cytotoxic effects of free curcumin (CM) and CM-NP were investigated on GSCs obtained during the removal of a brain tumor. Both CM and CM-NP caused a dose-dependent decrease in cell proliferation and viability of GSCs. The IC50 values of CM and CM-NP on GSCs were 50 and 137 µg/ml after 24 h, respectively. CM-NP exerted significantly higher effects on GSC viability, apoptosis, cell cycle arrest, and the expression of Bax, a pro-apoptotic marker, compared with CM. In addition, the migration of GSCs was significantly impaired following the administration of CM-NP compared with CM. Furthermore, CM-NP significantly increased the values of reactive oxygen species and decreased the mRNA expressions of NF-κB and IL-6 of GSCs compared with CM. Our data also revealed that CM-NP could significantly reduce the invasiveness of GSCs compared with CM, possibly via MCP-1-mediated pathways. In addition, CM-NP exhibited a significantly greater inhibitory effect on colony formation of GSCs compared with CM. These data indicate that CM-NP exhibited stronger anti-tumor effects on GSCs than CM. Although further in vivo investigations are warranted, our results suggest that CM-NP could be an ideal carrier to deliver curcumin for potential therapeutic approaches into glioblastoma.

Effects of Chrysin on Serum Corticosterone Levels and Brain Oxidative Damages Induced by Immobilization in Rat.

BACKGROUND: Chrysin (CH) is one of the main flavonoids of vegetables, fruits, and plants, the neuroprotective effect of which has been demonstrated in this study. OBJECTIVE: The aim of the current investigation is the evaluation of the impact of chrysin (CH) on serum corticosterone level. Additionally, depression due to chronic stress was studied in animal models. METHODS: The rats were restrained for 1 hour daily for 3 weeks. During these weeks, all animals were daily injected with either vehicle or CH (10, 20, 30 µg/kg). RESULTS: Present data indicated that the serum corticosterone levels markedly elevated in the stressed group versus the non-stressed group (p<0.001). The serum corticosterone levels were significantly lower in the stress-exposed rats administered with CH versus the stress-exposed non- CH-treated rats (p<0.05). In addition, immobility time significantly increased in the rats submitted to restraint stress versus the non-stressed group (p<0.001). Also, the number of crossing significantly decreased in the rats submitted to restraint stress versus non-stressed rats (p<0.001). The immobility time and the number of crossing were also reduced in the CH-administrated stressed rats (30 mg/kg) versus non-treated stressed group (p<0.001, p<0.05, respectively). CH also ameliorated the MDA and GSH content as well as antioxidant enzymes activities in stressed rats (p<0.05). CONCLUSION: The present study suggested that CH might be useful for the management of depressant-like effects induced by chronic stress via decreasing oxidative damage in the brain.

Predictive Value of Computed Tomography Scan for Posterior Ligamentous Complex Injuries in Patients with Thoracolumbar Spinal Fractures.

BACKGROUND: Thoracolumbar spinal fractures include a range of injuries of various severities from simple apophyseal fractures to neurological injury and complex fractures associated with vertebral dislocation. The treatment of thoracolumbar fractures is challenging, especially due to the difficulty of evaluating the posterior ligamentous complex (PLC). The purpose of this study was to evaluate the diagnostic value of computed tomography (CT) scan in predicting PLC injuries in the patients with thoracolumbar spinal fractures referring to the referral center of spinal trauma in the east north of Iran in 2016. METHODS: This retrospective study was conducted on patients with thoracolumbar injuries referring to Shahid Kamyab Hospital in Mashhad, east north of Iran, in 2016. The data were collected by entering the data of medical records into special forms. The classification of spinal fractures was accomplished using the AO Spine Classification System. RESULTS: According to the results, 71 (71.7%) patients were male, and the subjects had a mean age of 44.6±17.7 years. The PLC injury was observed in 28 (28.3%) patients. The PLC injury showed a significant relationship with facet joint widening, increased interspinous process distance, and spinous process avulsion fracture (P<0.05). CONCLUSION: As the findings of this study indicated, the diagnostic results of PLC injury by means of CT scan was similar to those obtained by magnetic resonance imaging in patients with thoracolumbar spinal fractures.

Transplantation of human meningioma stem cells loaded on a self-assembling peptide nanoscaffold containing IKVAV improves traumatic brain injury in rats.

Traumatic brain injury (TBI) can result in permanent brain function impairment due to the poor regenerative ability of neural tissue. Tissue engineering has appeared as a promising approach to promote nerve regeneration and to ameliorate brain damage. The present study was designed to investigate the effect of transplantation of the human meningioma stem-like cells (hMgSCs) seeded in a promising three-dimensional scaffold (RADA4GGSIKVAV; R-GSIK) on the functional recovery of the brain and neuroinflammatory responses following TBI in rats. After induction of TBI, hMgSCs seeded in R-GSIK was transplanted within the injury site and its effect was compared to several control groups. Application of hMgSCs with R-GSIK improved functional recovery after TBI. A significant higher number of hMgSCs was observed in the brain when transplanted with R-GSIK scaffold compared to the control groups. Application of hMgSCs seeded in R-GSIK significantly decreased the lesion volume, reactive gliosis, and apoptosis at the injury site. Furthermore, treatment with hMgSCs seeded in R-GSIK significantly inhibited the expression of Toll-like receptor 4 and its downstream signaling molecules, including interleukin-1ß and tumor necrosis factor. These data revealed the potential for hMgSCs seeded in R-GSIK to improve the functional recovery of the brain after TBI; possibly via amelioration of inflammatory responses. STATEMENT OF SIGNIFICANCE: Tissue engineered scaffolds that mimic the natural extracellular matrix of the brain may modulate stem cell fate and contribute to tissue repair following traumatic brain injury (TBI). Among several scaffolds, self-assembly peptide nanofiber scaffolds markedly promotes cellular behaviors, including cell survival and differentiation. We developed a novel three-dimensional scaffold (RADA16GGSIKVAV; R-GSIK). Transplantation of the human meningioma stem-like cells seeded in R-GSIK in an animal model of TBI significantly improved functional recovery of the brain, possibly via enhancement of stem cell survival as well as reduction of the lesion volume, inflammatory process, and reactive gliosis at the injury site. R-GSIK is a suitable microenvironment for human stem cells and could be a potential biomaterial for the reconstruction of the injured brain after TBI.

A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases.

BACKGROUND & OBJECTIVE: Medicinal plants have attracted great attention in the recent years and is increasingly applied instead of the chemical drugs. Several documents showed that herbal medicine traditionally and clinically applied in the cure and prevention of several diseases. In the recent years, different medicinal plants and their main components have been chosen in neurological therapy. The less toxic effects, availability, and lower price of medicinal plants versus synthetic substances make them as excellent and simple selection in the treatment of nervous diseases. Nigella sativa (N. Sativa) L. (Ranunculaceae), well recognized as black cumin, has been utilized as a medicinal plant that has a strong traditional background. Thymoquinone (TQ) is one of the main active components of the volatile oil of N. sativa seeds and most effects and actions of N. Sativa are mainly related to TQ. The several pharmacological properties of N. sativa and TQ have been found, for example; anti-tumor, anti-microbial, anti-histaminic, immunomodulatory, anti-inflammatory, and anti-oxidant effects. Many reviews have investigated this valuable plant and its components, but none of them focused on their neuroprotective effects. Therefore, the aim of the present review was to show comprehensive and neuropharmacological properties of N. sativa and TQ. In this review, various studies on scientific databases regarding the effects of N. sativa and TQ in neurological diseases have been introduced. Studies on the neuroprotective effects of N. sativa and TQ which were published between1979 and 2018, were searched using various databases. The results of these studies showed that N. sativa and TQ have the protective effects against neurodegenerative diseases, including; Alzheimer, depression, encephalomyelitis, epilepsy, ischemia, Parkinson, and traumatic brain injury have been discussed in the cell lines and experimental animal models. Although there are many studies indicating the beneficial actions of this plant in the nervous system, the number of research projects relating to the human reports is rare. CONCLUSION: Therefore, better designed clinical trials in humans are needed to confirm these effects.

Protective Effects of Crocetin on Depression-like Behavior Induced by Immobilization in Rat.

BACKGROUND & OBJECTIVE: Crocetin, an active ingredient of saffron, has been recognized as a potent antioxidant. Plant extracts or their components may be useful in ameliorating the various diseases, including neurodegenerative disorders. This study investigated the effects of crocetin on oxidative damage induced by chronic restraint stress in the rat brain. For this reason, rats were kept in the restrainers for 1 hour every day, for 21 consecutive days. The animals were injected crocetin (20, 40, 60 mg/kg) or vehicle daily for 21 days. Findings showed that the immobility time significantly increased in the rodents subjected to the chronic stress compared with the normal group. However, the number of crossing beams in the rats submitted to the chronic stress significantly decreased versus the non-stress rats. Treatment with crocetin ameliorated the immobility time and the number of crossing in the chronic restraint stress rats versus the non-treated stress group. Crocetin also reverted the levels of MDA and GSH and also the activities of antioxidant enzymes to the normal levels in the stress groups. CONCLUSION: The present study suggests that crocetin may be useful for the management of depressantlike effects induced by chronic stress through decreasing oxidative damage in the brain.

The Neuroprotective Effects of Thymoquinone: A Review.

Thymoquinone (TQ), one of the main components active of Nigella sativa, exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on. In addition, TQ protected brain cells from various injuries due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and experimental animal models. The present study has been designed to review the scientific literature about the pharmacological activities of TQ to the neurological diseases. This study purposed that although experimental studies indicated the beneficial effects of TQ against nervous system problems, better designed clinical trials in humans are needed to confirm these effects.

The protective effects of crocin in the management of neurodegenerative diseases: a review.

Flavonoids have been used in traditional medicine to promote human health. Crocin has been proposed to be effective in the management of the various diseases including the neurodegenerative diseases. Antiepileptic and anti-Alzheimer effects of crocin have also been indicated. The efficacy of crocis in the treatment of cerebral ischemia and traumatic brain injury was also confirmed by using animal models. Crocin treatment increased dopamine levels in the brain of experimental model of Parkinson's disease. In addition, crocin modulates the opioid system to decrease the withdrawal syndrome. Thus, the present study highlighted the effects of crocin on the nervous system and the underling mechanisms. This review also indicated that crocins can be considered as an effective candidate in the management of nervous system diseases due to their antioxidant and anti-inflammation effects.

Correction to: Laminin-derived Ile-Lys-Val-ala-Val: a promising bioactive peptide in neural tissue engineering in traumatic brain injury.

There is only one problem with Table 3. The references mentioned in this table were wrong in the final proof.

Laminin-derived Ile-Lys-Val-ala-Val: a promising bioactive peptide in neural tissue engineering in traumatic brain injury.

The adult brain has a very limited regeneration capacity and there is no effective treatment currently available for brain injury. Neuroprotective drugs aim to reduce the intensity of cell degeneration but do not trigger tissue regeneration. Cell replacement therapy is a novel strategy to overcome brain injury-induced disability. To enhance cell viability and neuronal differentiation, developing bioactive scaffolds combined with stem cells for transplantation is a crucial approach in brain tissue engineering. Cell interactions with the extracellular matrix (ECM) play a vital role in neuronal cell survival, neurite outgrowth, attachment, migration, differentiation, and proliferation. Thus, appropriate cell-ECM interactions are essential when designing and modifying scaffolds for application in neural tissue engineering. To improve cell-ECM interactions, scaffolds can be modified with bioactive peptides. Here, we discuss the characteristic features of laminin-derived Ile-Lys-Val-Ala-Val (IKVAV) sequence as a bio-functional motif in scaffolds and the behavior of stem cells in scaffolds conjugated with the IKVAV peptide. The incorporation of this bioactive peptide in nanofiber scaffolds markedly improves stem cell behavior and may be a potential method for cell replacement therapy in traumatic brain injury.

Anti-oxidative effects of safranal on immobilization-induced oxidative damage in rat brain.

Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. The present study was designed to investigate the effects of safranal against restraint stress induced oxidative damage in the rat brain. For inducing the chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days, then, the animals received systemic administrations of vehicle (0.1% DMSO) acted as the control group or safranal daily for 21days. Results indicated that the rats submitted to restraint stress showed an increase in the immobility time versus the non-stress rats. In addition, stress decreased number of crossing in the rats submitted to restraint stress versus the non-stress animals. Treatment with safranal (0.75mg/kg) showed a significant reduction in the immobility time compared to the non-treated stress group, while, the treatment improved the number of crossing in rats submitted to restraint stress versus the vehicle-treated stress rats. In the stressed animals that received vehicle, the MDA level was significantly higher and the levels of GSH and antioxidant enzymes were significantly lower than the non-stressed rats. Safranal ameliorated the changes in the stressed animals as compared with the control groups. The present findings indicate that safranal might be effective against depressant-like effects induced by chronic stress via modulating brain oxidative response.

The Role of Saffron in Attenuating Age-related Oxidative Damage in Rat Hippocampus.

BACKGROUND: Using antioxidant diets may be a good strategy for the inhibition of oxidative stress connected to age-related disease. Saffron is a dried stigma of with antioxidant properties. This investigation was done to study the effects of saffron administration on lipid peroxidation and antioxidant status in female aged rats. METHODS: The rats were treated with the ethanolic extract of saffron for 4 weeks. At the end of our investigation, the hippocampi of rats were removed. The homogenate was used for the evaluation of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxides (GPx), catalase (CAT) and glutathione (GSH). There are recent patents also suggesting the use of saffron and its gradients for prevention of oxidative stress in aged tissues. RESULT: The results showed that the aging was connected with a significant reduction in the activities of antioxidant enzymes, and an increase in MDA and nitric oxide levels in the hippocampus of aged rats. In addition, treatment of saffron was effective in reducing hippocampus MDA and NO levels and in increasing the antioxidant status. There is a possibility that saffron extract acts as a hormetin by inducing mild oxidative damage which leads to the activation of antioxidative enzymes. CONCLUSION: Therefore, saffron exerted considerable neuroprotective effect and proved to be efficacious in protecting rat hippocampus against age-related oxidative damage.