Therapeutic Effects of Low-Level Laser Therapy on Pain and Disability of Patients with Failed Back Surgery Syndrome.

Purpose: This study intended to evaluate the effects of Low-Level Laser Therapy (LLLT) on Failed Back Surgery Syndrome (FBSS). FBSS refers to symptoms and disabilities which remain or occur after lumbar spinal surgery. Prevalent treatments for FBSS are based mostly on conservative management while LLLT has gained significant interest in the treatment of a wide variety of musculoskeletal disorders. Methods: In the present study, the authors included 50 individuals with FBSS. Target points were determined by an ultrasonic study including bilateral L2-L3 through L5-S1 facet joints, sacroiliac joints, and the region immediately above bilateral supra crestal iliac bones representing cluneal nerves. LLLT was performed three times a week for 3 weeks. A near-infrared laser (wavelength 808 nm, power 500 mw) was used in continuous mode for laser therapy sessions. The Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) were registered before treatment and after last treatment session, 1 month and 6 months later, respectively. Results: NRS and ODI were significantly improved after treatment, as well as therapeutic effects, after 1 month and 6 months were also evident and comparison of the NRS and ODI showed significant difference. Conclusion: LLLT has a positive impact on pain and disability in patients with FBSS.

Effect of sex differences and time of oxytocin administration on treatment of rat model of autism spectrum disorder: Focused on necroptosis markers.

Autism is a neurodevelopmental disorder. A variety of molecular and cellular abnormalities leads to behavioral deficits in autism. Nevertheless, its etiology and treatment strategy are not completely understood. Oxytocin has recently shown improvements in social functioning. This study aimed to evaluate the necroptosis pathway for the neuroprotective effects of oxytocin in the valproic acid-induced autism spectrum disorder model. The autism spectrum disorder was induced by valproic acid on gestational day 12.5 (600 mg/kg, intraperitoneally). Offspring received intranasal oxytocin (1 µg/µL) on the 21st and 40th days after birth. The offspring behaviors were scrutinized by self-grooming, marble-burying, three-chamber, and Morris water maze tests. Western blot was performed on the hippocampus and amygdala tissues to investigate the expression of RIP3 and MLKL markers. The valproic acid group demonstrated more anxiety, repetitive behaviors, and expression of RIP3 and MLKL markers, and less social interaction and spatial memory compared with the control group. Oxytocin considerably improved social interactions, preference for social novelty, and memory. The elevated expression of RIP3 and MLKL markers in valproic acid-induced autistic rats were alleviated after treatment with oxytocin. We also highlighted the importance of age and gender in autism spectrum disorder interventions. Our findings suggested that oxytocin administration was as an effective treatment in two areas of repetitive/stereotyped behaviors, social interactions/cognitive function. Notably, early administration of oxytocin resulted in better therapeutic responses in autism-like behaviors. The molecular tests introduce oxytocin as a potential candidate for reducing the expression of necroptosis mediators in the brain. This reinforced our hypothesis that the necroptosis pathway takes part in autism spectrum disorder.

Effect of eugenol on lipid profile, oxidative stress, sex hormone, liver injury, ovarian failure, and expression of COX-2 and PPAR-α genes in a rat model of diabetes.

BACKGROUND: Diabetes is among the leading causes of reproductive system failure and infertility in both women and men. Inflammation and oxidative stress have a main role in the development of diabetes. Eugenol or clove oil is a phenolic monoterpenoid with antioxidant and anti-inflammatory properties. Here, the effects of eugenol on diabetes features and ovarian function were investigated. METHODS AND RESULTS: Streptozotocin-induced diabetes rats were treated with 12 and 24 mg/kg of eugenol for 4 weeks. The biochemical and histological assay was done to evaluate the effects of eugenol on ovary and pancreas function, liver injury, oxidative status, sex hormones, lipid profile, and mRNA levels of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor alpha (PPAR-α) genes. Streptozotocin increased levels of serum glucose, total cholesterol, triglyceride, low-density lipoprotein, aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, pancreas necrosis and inflammation, COX-2 expression, ovarian cystic, and anovulation. It decreased the levels of insulin, high-density lipoprotein, Superoxide dismutase, estradiol, progesterone, testosterone, luteinizing hormone, follicle-stimulating hormone, and PPAR-α expression. Eugenol administration ameliorated diabetes features through the improvement of lipid profile, oxidative status, insulin and glucose levels, sex hormone levels, liver markers, COX-2 and PPAR-α expression, and pancreas histology. It had no effect on ovarian cystic and follicular development. CONCLUSIONS: Therefore, eugenol may be useful for ameliorating some adverse features of diabetes and used as an adjunct treatment or protective agent accompany by other chemicals in diabetes patients.

Therapeutic Effects of Eugenol in Polycystic Ovarian Rats Induced by Estradiol Valerate: A Histopathological and A Biochemical Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common type of endocrinopathy in women which is accompanied by androgens elevation, insulin resistance, and metabolic dysfunction. Eugenol is a phenolic component of clove oil that has an antioxidant, anti-inflammatory, and anti-diabetic activity. The present study aimed to evaluate the therapeutic effects of eugenol on the PCOS models of rats. MATERIALS AND METHODS: In this experimental study, thirty adults female Wistar rats weighing between 180 and 200 g were used. Estradiol valerate-induced PCOS rats (4 mg/rat) were treated with eugenol (12 and 24 mg/kg) for 28 days. The effects of eugenol were studied on levels of glucose, lipid profile, liver enzymes, reproductive hormones, oxidative stress, and the expression of cyclooxygenase-2 (Cox-2) and peroxisome proliferator-activated receptor alpha (Ppar-α) genes, using biochemical analysis of blood and histopathological evaluation of ovaries.
Results: Estradiol valerate-induced PCOS resulted in the formation of cystic follicles in the ovaries, hyperinsulinemia, hyperglycemia, hyperlipidemia, hyperandrogenism, and anovulation. It altered the Cox-2 and Ppar-α gene expression and increased oxidative stress and activities of liver enzymes. Eugenol treatment improved the PCOS-associated endocrine and metabolic disorder and histopathological alterations, mostly through antioxidant, anti-diabetic, anti hyperlipidemic, and anti-androgenic properties. It showed beneficial effects on serum glucose, serum insulin, fat profile, reproductive hormones, liver activity, oxidative stress, expression of Cox-2 and Ppar-α genes, as well as restoration of normal ovulation in the PCOS animals.
Conclusion: Eugenol could represent a promising natural product to prevent PCOS or reduce its symptoms.

All-Trans Retinoic Acid-Preconditioned Mesenchymal Stem Cells Improve Motor Function and Alleviate Tissue Damage After Spinal Cord Injury by Inhibition of HMGB1/NF-κB/NLRP3 Pathway Through Autophagy Activation.

Spinal cord injury (SCI) is a significant public health issue that imposes numerous burdens on patients and society. Uncontrolled excessive inflammation in the second pathological phase of SCI can aggravate the injury. In this paper, we hypothesized that suppressing inflammatory pathways via autophagy could aid functional recovery, and prevent spinal cord tissue degeneration following SCI. To this end, we examined the effects of intrathecal injection of all-trans retinoic acid (ATRA)-preconditioned bone marrow mesenchymal stem cells (BM-MSCs) (ATRA-MSCs) on autophagy activity and the HMGB1/NF-κB/NLRP3 inflammatory pathway in an SCI rat model. This study demonstrated that SCI increased the expression of Beclin-1 (an autophagy-related gene) and NLRP3 inflammasome components such as NLRP3, ASC, Caspase-1, and pro-inflammatory cytokines IL-1ß, IL-18, IL-6, and TNF-α. Additionally, following SCI, the protein levels of key autophagy factors (Beclin-1 and LC3-II) and HMGB1/NF-κB/NLRP3 pathway factors (HMGB1, p-NF-κB, NLRP3, IL-1ß, and TNF-α) increased. Our findings indicated that ATRA-MSCs enhanced Beclin-1 and LC3-II levels, regulated the HMGB1/NF-κB/NLRP3 pathway, and inhibited pro-inflammatory cytokines. These factors improved hind limb motor activity and aided in the survival of neurons. Furthermore, ATRA-MSCs demonstrated greater beneficial effects than MSCs in treating spinal cord injury. Overall, ATRA-MSC treatment revealed beneficial effects on the damaged spinal cord by suppressing excessive inflammation and activating autophagy. Further research and investigation of the pathways involved in SCI and the use of amplified stem cells may be beneficial for future clinical use.

Apelin-13 protects against memory impairment and neuronal loss, Induced by Scopolamine in male rats.

The present study aimed to evaluate the effects of Apelin-13 on scopolamine-induced memory impairment in rats. Forty male rats were divided into five groups of eight. The control group received no intervention; the scopolamine group underwent stereotaxic surgery and received 3 mg/kg intraperitoneal scopolamine. The treatment groups additionally received 1.25, 2.5 and 5 µg apelin-13 in right lateral ventricles for 7 days. All rats (except the control group) were tested for the passive avoidance reaction, 24 h after the last drug injection. For histological analysis, hippocampal sections were stained with cresyl violet; synaptogenesis biochemical markers were determined by immunoblotting. Apelin-13 alleviated scopolamine-induced passive avoidance memory impairment and neuronal loss in the rats' hippocampus (P<0.001). The reduction observed in mean concentrations of hippocampal synaptic proteins (including neurexin1, neuroligin, and postsynaptic density protein 95) in scopolamine-treated animals was attenuated by apelin-13 treatment. The results demonstrated that apelin-13 can protect against passive avoidance memory deficiency, and neuronal loss, induced by scopolamine in male rats. Further experimental and clinical studies are required to confirm its therapeutic potential in neurodegenerative diseases.

Dopamine D1 Receptor-Mediated Regulation of Per1, Per2, CLOCK, and BMAL1 Expression in the Suprachiasmatic Nucleus in Adult Male Rats.

Photic and non-photic inputs are reported to affect clock gene expressions and behavioral activities in the SCN. However, it is not known whether dopaminergic input mediates these regulatory effects on clock genes. The present study examined the molecular effects of dopamine D1 agonist on Per1, Per2, CLOCK, and Bmal1 expressions in the SCN and its effect on behavioral activities to determine the role of dopamine D1 receptor in regulation of these gene expressions and behavioral activities in adult male Wistar rats. To examine the molecular effects of dopamine D1 agonist day and night, we injected 20 mg/kg SKF38393 to the first group of rats at 6 a.m. and the second group at 6 p.m. We also injected saline to the third and fourth groups of rats at 6 a.m. and 6 p.m. as control groups. All rats were sacrificed 2 h following the injections. The real-time PCR technique was used to evaluate the clock gene expression. In addition, to examine the effects of dopamine D1 agonists on behavioral activities, we injected 20 mg/kg SKF38393 to SKF receiving group and saline to control group. The behavioral activities of the rats were monitored on the running wheel for 21 days, 1 week following the injections. SKF injections increased the Per2 and CLOCK expressions in the daytime and significantly decreased the Per1 and Bmal1 expressions. However, at night, SKF injections increased only Per2 expressions significantly and decreased the Per1, CLOCK, and Bmal1 genes expressions. Both saline receiving groups showed that all gene expressions were significantly higher except Per2 during nighttime. SKF injection increased the running wheel activity during nighttime significantly. Based on the obtained result, clock gene expression and behavioral activities in adult male Wistar rats may be altered or monitored by administration of exogenous dopamine.

ß-Amyloid Formation, Memory, and Learning Decline Following Long-term Ovariectomy and Its Inhibition by Systemic Administration of Apigenin and ß-Estradiol.

INTRODUCTION: The increasing cases of Alzheimer Disease (AD) has caused numerous problems. The risk of developing AD increases in menopausal women, too. Apigenin and ß-estradiol are effective antioxidant and neuroprotective agents. We conducted the present study to explore their combined effects on ß-amyloid plaque formation, memory, and learning in ovariectomized rats. METHODS: Forty-two Wistar rats were randomly assigned into 6 groups: 1) ovariectomized (OVX), 2) OVX + apigenin, 3) OVX + ß-estradiol, 4) OVX + apigenin + ß-estradiol, 5 &6) vehicle shams for E2 and API, and 7) surgical sham. Treatment was done with apigenin and ß-estradiol. Then, we studied the formation of ß-amyloid plaques, neuronal density in the hippocampus area, apoptosis, memory, and learning. RESULTS: Findings showed the significant formation of ß-amyloid plaques in the hippocampus of OVX animals and their memory impairment. Apigenin and ß-estradiol significantly reduced the number of ß-amyloid plaques, as well as the symptoms of memory impairment and learning, and decreased the expression of caspase-3 in treated animals. CONCLUSION: Accordingly, ß-estradiol and apigenin could have more potent therapeutic effects on AD.

The Effect of Resistance Training and Berberine Chloride on the Apoptosis-related Unfolded Protein Response Signaling Pathway in the Hippocampus of Diazinon-poisoned Rats.

INTRODUCTION: Diazinon is one of the most widely-used organophosphate pesticides in the world. This toxin enters the body in various ways and induces oxidative stress in various tissues. It has been proved that activation of Unfolded Protein Response (UPR) under oxidative stress is a steady mechanism for maintaining cell function and survival. Therefore, the present study aimed to review the effect of Resistance Training (RT) and Berberine Chloride (BC) on the apoptosis-related UPR signaling pathway in the hippocampus of diazinon-poisoned rats. METHODS: In this experimental study, 40 male Wistar rats weighing 250 ±50 g were randomly divided into eight groups of five rats of 1) diazinon + 2 mg/kg BC + RT, 2) diazinon + 15 mg/kg BC + RT, 3) diazinon, 4) diazinon + RT, 5) diazinon + 2 mg/kg BC, 6) diazinon + 15 mg/kg BC, 7) healthy control, and 8) sham. The groups were treated for 5 weeks. At the end of the fifth week, ATF-4, ATF-6, and CHOP gene expression in hippocampus tissue were measured by quantitative real-time RT-PCR. RESULTS: Diazinon significantly increased the expression of ATF-4, ATF-6, and CHOP in the hippocampus tissue of rats. Administrating 15 mg/kg BC with RT significantly decreased these genes, indicating a decrease in the rate of apoptosis in the hippocampus. CONCLUSION: This study showed that RT and BC have a protective effect against diazinon-induced toxicity in the hippocampus.

Neurogenesis in the rat neonate's hippocampus with maternal short-term REM sleep deprivation restores by royal jelly treatment.

BACKGROUND: Numerous studies have shown the effects of rapid eye movement sleep deprivation (REM-SD) on behavior and brain structures. The impact of REM-SD on learning and memory, thus neurogenesis, has been reported in previous studies. Royal jelly (RJ) is known as the wealthiest biological nutrient with various physiological properties. This study aimed to study the possible effect of RJ on neurogenesis of the rat hippocampus neonates following exposure of mother to REM-SD during pregnancy. METHODS: Thirty neonate rats from 15 pregnant Wistar rats were used. To induce REM-SD, the flowerpot method was used. The pregnant rats were divided into five groups (n = 3): group 1, no treatment; group 2, REM-SD; groups 3, 4, and 5, REM-SD +RJ. The former group received 72 h REM-SD during pregnancy (days 7, 14, 21), and the latter group received REM-SD + RJ (three trial groups). At week 4, the rat neonates of all groups were sacrificed (n = 6 each group). Their brains were fixed, removed, and prepared for Nissl and Hoechst 33342 staining. By using real time polymerase chain reaction methode the brain-derived neurotrophic factor BDNF gene expression was studied (RT-PCR), brain-derived neurotrophic factor (BDNF) gene expression was studied. The results were analyzed statistically, and the Pv  < .05 was considered significant. RESULTS: The results showed a significant decrease in the number of neurons in the hippocampus of neonatal rats of REM-SD mothers compared to the neonates of the mother with REM-SD + RJ. REM-SD also led to an increase in apoptosis reaching the neonates from the REM-SD + RJ animals. High expression of BDNF was observed in the hippocampus of the neonates from REM-SD + RJ treated mothers. CONCLUSION: RJ acts as a neuroprotective agent that could compensate for the effects of REM-SD on learning and memory via restoring neurogenesis.

More attention on glial cells to have better recovery after spinal cord injury.

Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury.

The effectiveness of continuous and interval exercise preconditioning against chronic unpredictable stress: Involvement of hippocampal PGC-1α/FNDC5/BDNF pathway.

Various exercise-training types are known to prevent depression, but mechanisms underlying their beneficial effects remain unknown. In the present study, the preconditioning effect of continuous and interval exercise on stress-induced depression was evaluated. Adult male Wistar rats in the exercise groups were made to run on a motorized treadmill, five sessions per week for six weeks. After that, to induce the depression model, the rats were exposed to chronic unpredictable stress for three weeks. Behavioral tests were assessed by open field, elevated plus maze, and forced swim tests. Hippocampal PGC-1α, FNDC5, and BDNF protein expression by Western blot and serum corticosterone by ELISA were detected. In the present results, after continuous and interval exercise periods, locomotor activity, the number of entries and time spent in the open arms were increased, and immobility time was significantly reduced. PGC-1α, FNDC5, and BDNF protein levels had a significant increase, and serum corticosterone did not change. Also, interval exercise training increased PGC-1α and FNDC5 more than continuous. Chronic unpredictable stress reduced the positive changes caused by exercise training, although, except FNDC5, exercise preconditioned groups experienced less significant adverse changes in most variables. These findings showed that both continuous and interval exercise preconditioning with increasing hippocampal PGC-1α, FNDC5, and BDNF proteins and improve the anxiety- and depression-like behaviors have a protective effect against chronic unpredictable stress.

Comparing various protocols of human and bovine ovarian tissue decellularization to prepare extracellular matrix-alginate scaffold for better follicle development in vitro.

BACKGROUND: Nowadays, the number of cancer survivors is significantly increasing as a result of efficient chemo/radio therapeutic treatments. Female cancer survivors may suffer from decreased fertility. In this regard, different fertility preservation techniques were developed. Artificial ovary is one of these methods suggested by several scientific groups. Decellularized ovarian cortex has been introduced as a scaffold in the field of human fertility preservation. This study was carried out to compare decellularization of the ovarian scaffold by various protocols and evaluate the follicle survival in extracellular matrix (ECM)-alginate scaffold. RESULTS: The micrographs of H&E and DAPI staining confirmed successful decellularization of the ovarian cortex in all experimental groups, but residual DNA content in SDS-Triton group was significantly higher than other groups (P < 0.05). SEM images demonstrated that complex fiber network and porosity structure were maintained in all groups. Furthermore, elastin and collagen fibers were observed in all groups after decellularization process. MTT test revealed higher cytobiocompatibility of the SDS-Triton-Ammonium and SDS-Triton decellularized scaffolds compared with SDS groups. Compared to the transferred follicles into the sodium alginate (81%), 85.9% of the transferred follicles into the decellularized scaffold were viable after 7 days of cultivation (P = 0.04). CONCLUSION: Although all the decellularization procedures was effective in removal of cells from ovarian cortex, SDS-Triton-Ammonium group showed less residual DNA content with higher cytobiocompatibility for follicles when compared with other groups. In addition, the scaffold made from ovarian tissues decellularized using SDS-Triton-Ammonium and sodium alginate is suggested as a potential 3D substrate for in vitro culture of follicles for fertility preservation.

Related Fluoxetine and Methylprednisolone Changes of TNF-α and IL-6 Expression in The Hypothyroidism Rat Model of Spinal Cord Injury.

OBJECTIVE: Spinal cord injury (SCI) is a serious clinical condition that leads to disability. Following primary injury, proinflammatory cytokines play an important role in the subsequent secondary events. The thyroid hormone (TH) is known as the modulator of inflammatory cytokines and acts as a neuroprotective agent. Methylprednisolone (MP) is used for the early treatment of SCI. Fluoxetine (FLX), also is known as a selective serotonin reuptake inhibitor (SSRI), has therapeutic potential in neurological disorders. The aim of the present study was to investigate the combined effects of MP and FLX on SCI in the rat hypothyroidism (hypo) model. MATERIALS AND METHODS: In this experimental study, 48 male Wistar rats with hypothyroidism were randomly divided into 6 groups (n=8/group): control (Hypo), Hypo+Surgical sham, Hypo+SCI, Hypo+SCI+MP, Hypo+SCI+FLX, and Hypo+SCI+MP+FLX. SCI was created using an aneurysm clip and Hypothyroidism was induced by 6-Propyl-2-thiouracil (PTU) at a dose of 10 mg/kg/day administered intraperitoneally. Following SCI induction, rats received MP and FLX treatments via separate intraperitoneal injections at a dose of 30 and 10 mg/kg/day respectively on the surgery day and FLX continued daily for 3 weeks. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were quantified by Real-time polymerase chain reaction (PCR) and Western blotting. Myelination and glutathione (GSH) levels were analyzed by Luxol Fast Blue (LFB) staining and ELISA respectively. RESULTS: Following combined MP and FLX treatments, the expression levels of TNF-α and IL-6 significantly decreased and GSH level considerably increased in the trial animals. CONCLUSION: Our results show the neuroprotective effects of MP and FLX with better results in Hypo+SCI+MP+FLX group. Further study is required to identify the mechanisms involved.

Combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by chlorpyrifos.

The aim of this study was to investigate the combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by CPF. 64 adult male albino rats were randomly selected and devided into eight groups of eight including: control, exercise (EXE), chlorpyrifos (CPF), Control + Oil (Co + Oil), Control + DMSO (Co + DMSO), chlorpyrifos + eugenol (CPF + Sup), chlorpyrifos + exercise (CPF + Exe) and, chlorpyrifos + exercise + eugenol (CPF + Exe + Eu). Four experimental groups received intraperitoneal injection (5 days a week) of 3.0 mg/kg body weight CPF in DMSO for 6 consecutive weeks. The exercise groups performed aerobic 5 days per week over 4 weeks. Eugenol were administered by gavage. Finally, the animals were sacrificed using CO2 gas (a half of the rats were anesthetized with ketamine and xylazine and then perfused) to evaluate hippocampus histology and parameters. The results of this study showed that CPF injection significantly decreased BDNF, AChE and ATP in CA1 area of the hippocampus (p ˂ 0.05). Also, CA1 apoptosis by tunnel assay, it was found that CPF receiving groups with different dosage, showed a significant increase compared to other groups, which was confirmed by increasing cytochrome C and procaspase-3 in CPF groups (p ˂ 0.05). The result of this study show that 4 weeks of exercise training and eugenol supplementation does not improve the destructive effects of CPF in CA1 area of the hippocampus. As a result, it is recommended that future studies longer periods for treatment with exercise and eugenol supplementation.

Glioblastoma U-87MG tumour cells suppressed by ZnO folic acid-conjugated nanoparticles: an in vitro study.

Glioblastoma Multiform (GBM) known as the most common CNS malignant tumour. Therapy for GBM includes maximum tumour resection and chemotherapy. Recent advances have emphasized the use of nanoparticles, such as zinc oxide nanoparticles (ZnO-NPs). Conjugated ZnO NPs with folic acid (FA) easily pass through cell membrane. In the present study, ZnO NPs-FA applied to GBM U87MG cell line. ZnO NPs-FA synthesized according to the sol-gel method. The GBM U87MG and astrocytes 1321N1 cell lines cultured and divided into control, sham and ZnO NPs-FA groups. MTT assay used for the cell viability, and ROS assay and flow cytometry exploited. The size of nanoparticles was ≤20 nm using TEM and FTIR. After 12 hours, the viability for U87MG cells showed a significant decrease at 1.25 and 2.5 mg/ml concentrations. However, no such results obtained for astrocytes. According to the results, the ROS assay caused a significant increase in GBM cells at the mentioned concentration. It was concluded that dose-dependent conjugated NPs could play a therapeutic role in cancer therapy.

Neuroprotective effect of exogenous melatonin on the noradrenergic neurons of adult male rats' locus coeruleus nucleus following REM sleep deprivation.

Melatonin is primarily secreted by the pineal gland in dark. In addition to its role as an internal sleep facilitator, melatonin acts as an antioxidant, anti-inflammatory and neuroprotective agents. melatonin has been introduced as a therapeutic strategy for sleep disorders. Hence, in the present study, we studied the neuroprotective effects of pre- and post-treatment of melatonin in locus coeruleus nucleus (LC) of rapid eye movement (REM) sleep deprived (REM-SD) male adult rats. Adult male rats of control, sham and trial groups were used Exogenous melatonin (ExMe) was intraperitoneally injected in two forms of pre and post treatment. The protein level of cleaved caspase-3, the number and density of tyrosine hydroxylase (TH) positive neurons and the microglia population in LC were studied by western blot and immunohistochemistry respectively. Morphological changes of LC nucleus and its neurons were also studied by using stereological analysis. The number of neurons and volume of LC was reserved in animals that had received post-RSD ExMe. Apoptosis significantly was decreased comparing to RSD and Pre-RSD animals. Melatonin post-treatment of RSD rats also decreased cleavage of caspase-3 and increased reduced glutathione content in LC. Moreover, immunohistochemistry analysis showed an increase in the number of TH positive neurons and a decrease in microglia migration. Based on our findings antioxidant properties of exogenous melatonin could play a critical role in certain types of sleep disorders.

Simultaneous use of sensory stimulation and motor exercise improves the manual skills of educable children with mental retardation at preprimary and primary school levels.

Background: Children with mental retardation have various clinical problems. They mostly have motor delay and sensory deficit. Neurorehabilitation focuses on restoring remaining abilities. Thus, the present study was designed to study the effects of simultaneous use of sensory-motor therapy on manual skills of children with mental retardation. Methods: In this study, 120 educable boys and girls with mental retardation (9-12 years) were selected from 2 preprimary and primary exceptional centers in Tehran using stratified sampling method considering the geographical dispersion. The participants were divided into 2 equal trial and control groups using simple random sampling. Lincoln-Oseretsky Motor Development Scale, Purdue Pegboard test, and Handwriting Legibility Checklist of Persian Language were used. Simultaneous sensory stimulations and motor exercises were used for 3 one-hour weekly sessions for 12 consecutive weeks. Pre and posttests were done for evaluation. Using parametric paired and independent samples t tests, the findings were analyzed in SPSS 23. Results: The manual skills significantly improved following therapeutic use of simultaneous sensory stimulation and motor exercise (p=0.001). In the control group, the pre and post evaluation difference was not significant (p=0.813) Conclusion: Based on the findings of this study, simultaneous use of sensory-motor techniques can have better clinical results in the trial group compared to the control group. Thus, these types of techniques should be used more in clinics. However, further studies are needed for more comparison between separate applications of these techniques.

FNDC5 expression in Purkinje neurons of adult male rats with acute spinal cord injury following treatment with methylprednisolone.

Spinal cord injury (SCI) is a serious and complex medical condition that can happen to anyone. At present, therapy mainly focuses on rehabilitation and pharmacological treatment, such as methylprednisolone (MP). Supra-spinal changes in certain structures, such as the cerebellum, that receive many afferents from the spinal cord might be one reason for unsuccessful therapeutic outcomes. Recently, the expression of FNDC5 was reported in cerebellar Purkinje cells as a possible neuroprotective agent. In the present study, we considered the expression of FNDC5 in Purkinje cells following SCI with and without MP administration in adult rats with SCI. Thirty-five adult male rats were used in this study. The animals were randomly allocated into five groups, including SCI, spinal cord injury with methylprednisolone treatment (SCI + MP), operation sham, control, and operation sham with MP. Induction of SCI was achieved by using special clips to compress the spinal cord at a determined level. After a certain interval time, the animals underwent study for FNDC5 expression, apoptosis by using immunohistochemistry, Western blotting, and TUNEL and Nissl staining. Our results showed a significant decrease in the number of Purkinje cells following SCI. Therapy with MP inhibits apoptosis in irFNDC5 Purkinje cells and restores them. Expression of FNDC5 significantly increased in SCI and decreased following MP therapy. We also showed other cerebellar cells with FNDC5 immunoreactivity in the two other cerebellar layers that were firstly reported. Since irisin is known as a plasma product of FNDC5, we think it might be a plasma marker following therapeutic efforts for SCI; however, it needs further research. In addition, it is possible that changes in FNDC5 expression in Purkinje cells might be related to neurogenesis in the cerebellum with unknown mechanisms.

Coenzyme Q10 Influences on the Levels of TNF-α and IL-10 and the Ratio of Bax/Bcl2 in a Menopausal Rat Model Following Lumbar Spinal Cord Injury.

The roles of the immune response and apoptosis as potential mediators of secondary damage in spinal cord injury (SCI) are being investigated. Research is also being done to determine the effects of female gonadal steroids, which decrease during menopause, and antioxidants, such as coenzyme Q10 (CoQ10) on SCI. We hypothesized that in the absence of female gonadal steroids, which provide protection following an SCI, CoQ10 could modulate the expression of cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-10, besides aquaporin-4 (AQP4) water channels in the CNS, which participate in neuroinflammation, as well as the Bax and Bcl2 proteins that are involved in apoptosis at the site of injury. The spinal cord was compressed at the level of the T10 vertebrae and rats were treated by 10 mg/kg/day CoQ10 for 3 weeks after surgery. The TNF-α and IL-10 expressions were studied using an ELISA. Western blot was used to investigate the Bax/Bcl-2 ratio, AQP4. The level of TNF-α significantly decreased following the administration of CoQ10 compared with the level of IL-10. When the treatment group was compared with the OVX-SCI group, the ratio of Bax/Bcl2 significantly decreased in the groups (P < 0.01). Based on our findings, CoQ10 could be used to compensate for the absence of the neuroprotection effects provided by female gonadal steroids via reducing the inappropriate effects of the two main pathways of secondary damage in SCI apoptosis.