Stem cell therapy combined with luteolin alleviates experimental neuropathy.

Neuropathic pain is a chronic condition that causes long-term burning sensations. Despite significant efforts, current treatments for neuropathic pain are ineffective in curing the condition, which means new therapeutic options must be developed. One such option is the use of stem cell therapy in combination with anti-inflammatory herbal components, which has shown promise in treating neuropathic pain. The study aimed to investigate the effects of bone marrow mesenchymal stem cells (BM-MSCs) with luteolin on sensory deficits and pathological changes in a neuropathic model. The results showed that luteolin, either alone or in combination with BM-MSCs, effectively reduced sensory deficits related to mechanical and thermal hypersensitivity. In addition, luteolin alone and combined with BM-MSCs reduced oxidative stress in neuropathic rats and inhibited cellular responses, particularly reactive astrocytes. The study concluded that combining luteolin and BM-MSCs may offer an effective therapeutic strategy for patients with neuropathic pain, although further research is needed.

Co-transplantation of novel Nano-SDF scaffold with human neural stem cells attenuates inflammatory responses and apoptosis in traumatic brain injury.

Traumatic brain injury (TBI) causes long-term disability and mortality worldwide. The prime pathological players in TBI are neuroinflammation and apoptosis. These pathological changes lead to a limited capacity of regeneration after TBI. To alleviate inflammatory responses and apoptosis triggered by TBI, developing bioactive scaffolds conjoined with stem cells is a decisive approach in neural tissue engineering. The aim of this study was to fabricate a novel nano-scaffold made of RADA-16 with a bioactive motif of stromal cell-derived factor-1 α (SDF-1α) and evaluate its effects with stem cell transplantation on inflammatory pathways, reactive gliosis, and apoptosis after TBI. Co-transplantation of Nano-SDF and human neural stem cells (hNSCs) derived from fetus brain in adult rats subjected to TBI led to the improvement of motor activitycompared with the control group. The treated animals with hNSCs + Nano-SDF had a significantly lower expression of toll-like receptor 4 and nuclear factor-kappa B at the injury site than the control animals. A significant reduction in the number of reactive astrocytes was also observed in rats that received hNSCs + Nano-SDF compared with the vehicle and Nano-SDF groups. Furthermore, the TUNEL assay indicated a significant reduction in TUNEL positive cells in the hNSCs + Nano-SDF group compared with the TBI, vehicle, and Nano-SDF groups. These data demonstrated co-transplantation of hNSCs with Nano-SDF can reduce inflammatory responses and cell death after TBI via creating a more supportive microenvironment. Further research is required to establish the therapeutic efficacy of Nano-SDF with stem cells for TBI.

Dual Role of Fibroblast Growth Factor Pathways in Sleep Regulation.

Sleep plays an important function in neuro-immuno-endocrine homeostasis. Sleep disorders have been associated with an increased risk of metabolic and cognitive impairments. Among different factors that have an effect on sleep metabolism, a growing body of literature has investigated growth factors in the course of sleep quality and disorders. A good example of growth factors is fibroblast growth factors (FGFs), which are a large family of polypeptide growth factors. Evidence has shown that FGFs are involved in the modulation of sleep-wake behavior by their receptor subtypes and ligands, e.g., FFG1 plays an important role in the quality of sleep through somnogenic effects, while the high level of FGF23 is associated with secondary disorders in shift workers. Therefore, a controversial effect of FGFs can be seen in the course of sleep in physiologic and pathologic conditions. Further investigation on this topic would help us to understand the role of FGFs in sleep disorders as a therapeutic option and biomarker.

Health Crisis in Gaza: The Urgent Need for International Action.

The current and ongoing conflict imposed in Gaza has led to severe environmental challenges in Gaza, resulting in a health crisis that demands immediate attention and intervention. A comprehensive study has evaluated the pressing mental health, water and sanitation, access to healthcare, and infectious disease challenges plaguing the region. Mental health issues, particularly among children and adolescents, have surged in the wake of the conflict, with trauma-related symptoms expected to persist. The water and sanitation crises pose severe public health hazards, with an overwhelming majority of water unfit for consumption and escalating infectious diseases. Shortages of medicines, fuel, and breakdowns have profoundly affected access to healthcare in healthcare facilities, significantly impacting women and girls. The academic society is responsible for conducting research, providing education, and training, and advocating for policy changes. At the same time, the united nation's (UN) role is vital in providing aid, advocating for policy changes, and monitoring human rights and health situations. Urgent action is imperative to stabilize the environmental and health impacts and allow humanitarian aid into Gaza to alleviate the severe health problems. This study underlines the critical need for international support and intervention to address the multifaceted health crises in Gaza and prevent further deterioration.

The effect of combination pretreatment of donepezil and environmental enrichment on memory deficits in amyloid-beta-induced Alzheimer-like rat model.

Alzheimer's disease (AD) is progressive neurodegeneration known as the most common cause of dementia, and it is the sixth leading cause of death in older people. Given the promising data on the additive effect of combination therapy with donepezil (Aricept), an acetylcholinesterase inhibitor (AChEI), and regarding the similar neuronal mechanisms through which donepezil (DON) and environmental enrichment (EE) exert their enhancing effects on cognition; we asked whether simultaneous treatment with two paradigms in amyloid-beta-induced AD rats may lead to greater protection against the cognitive impairments than either treatment individually. The experimental groups consisted of Alz, sham-operated, Alz + DON, Alz + EE, and Alz + DON + EE. AD was induced by intrahippocampal injection of amyloid-beta (1-42, 6 µg), and DON was orally administrated (4 mg/kg) for 21 days. Environmental enrichment consisted of housing animals in large cages (50 × 50 × 50 cm) containing a running wheel and differently shaped objects for 21 days. Spatial learning and memory were assessed in the Morris water maze (MWM) and Real-time PCR was performed to assess the expression of brain-derived neurotrophic factor (BDNF) and M1 muscarinic acetylcholine receptor (AchM1R) within the hippocampus. Spatial memory was impaired in Alz animals, and while neither pretreatment with DON nor EE alone could significantly restore spatial memory scores in Alz rats, combination therapy was effective. BDNF expression was suppressed in Alz rats and pretreatment with DON plus EE could increase it to the saline levels. The data suggest that a cholinesterase inhibitor and cognitive stimulation can be used effectively in combination to protect cognitive loss in an AD rat model. This additive protective effect may be in part due to the augmented influence of this combination on BDNF levels and cholinergic neuronal system within the hippocampus.

Adrenal histological and functional changes after hepatic encephalopathy: From mice model to an integrative bioinformatics analysis.

Hepatic encephalopathy (HE), which is caused by neurotoxin agents in the liver, is a complicated condition with a variety of neurological manifestations. Recently, endocrine alterations have been more paid attention to for neurological severity in the course of HE, e.g. adrenal gland. To identify the role of adrenal gland in the context of HE, we evaluated the functional changes of adrenal gland (i.e., plasma corticosterone concentrations and histopathological changes) in mice model of HE. To dig deep into the molecular and genetic underpinnings, a comprehensive enrichment analysis for shared genes between HE and adrenal insufficiency (AI) was also performed. Our results showed a significant reduction in the level of plasma corticosterone and severe cellular necrosis in zona fasciculate of adrenal cortex, possibly indicating adrenal insufficiency. Enrichment analysis indicated four common genes, besides predicted five novel genes and some significant MicroRNAs (miRNAs) and transcription factors for both HE and AI. Couples with, several biological processes, such as DNA damage, inflammatory responses, glycolytic processes, and insulin receptor signaling pathway were predicted in both HE and AI. To sum up, data from experimental tests and bioinformatics analyses suggest that AI play an important role in the pathogenesis and progression of HE.

STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive-Compulsive Disorder.

Background: There are no data available on the levels of genetic networks between obsessive-compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in the pathogenesis of OCD in MS. Methods: To obtain gene-gene interactions for MS and OCD, the STRING database was used. Cytoscape was then used to reconstruct and visualize graphs. Then, ToppGene and Enrichr were used to identify the main pathological processes and pathways involved in MS-OCD novel genes. Additionally, to predict transcription factors and microRNAs (miRNAs), the Enrichr database and miRDB database were used, respectively. Results: Our bioinformatics analysis showed that the signal transducer and the activator of transcription 3 (STAT3) and neurotrophic receptor tyrosine kinase 2 (NTRK2) genes had connections with 32 shared genes between MS and OCD. Furthermore, STAT3 and NTRK2 had the greatest enrichment parameters (i.e., molecular function, cellular components, and signaling pathways) among ten hub genes. Conclusions: To summarize, data from our bioinformatics analysis showed that there was a significant overlap in the genetic components of MS and OCD. The findings from this study make two contributions to future studies. First, predicted mechanisms related to STAT3 and NTRK2 in the context of MS and OCD can be investigated for pharmacological interventions. Second, predicted miRNAs related to STAT3 and NTRK2 can be tested as biomarkers in MS with OCD comorbidity. However, our study involved bioinformatics research; therefore, considerable experimental work (e.g., postmortem studies, case-control studies, and cohort studies) will need to be conducted to determine the etiology of OCD in MS from a mechanistic view.

Neural stem cell therapy in conjunction with curcumin loaded in niosomal nanoparticles enhanced recovery from traumatic brain injury.

Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Recently, stem cell therapy has emerged as a new avenue to address neuronal regeneration after TBI. However, the environment of TBI lesions exerts negative effects on the stem cells efficacy. Therefore, to maximize the beneficial effects of stem cells in the course of TBI, we evaluated the effect of human neural stem/progenitor cells (hNS/PCs) and curcumin-loaded niosome nanoparticles (CM-NPs) on behavioral changes, brain edema, gliosis, and inflammatory responses in a rat model of TBI. After TBI, hNS/PCs were transplanted within the injury site and CM-NPs were orally administered for 10 days. Finally, the effect of combination therapy was compared to several control groups. Our results indicated a significant improvement of general locomotor activity in the hNS/PCs + CM-NPs treatment group compared to the control groups. We also observed a significant improvement in brain edema in the hNS/PCs + CM-NPs treatment group compared to the other groups. Furthermore, a significant decrease in astrogliosis was seen in the combined treatment group. Moreover, TLR4-, NF-κB-, and TNF-α- positive cells were significantly decreased in hNS/PCs + CM-NPs group compared to the control groups. Taken together, this study indicated that combination therapy of stem cells with CM-NPs can be an effective therapy for TBI.

The alteration of neuronal activities of the cuneiform nucleus in non-hypovolemic and hypovolemic hypotensive conditions.

BACKGROUND: The cuneiform nucleus is located in the center of the circuit that mediates autonomic responses to stress. Hemorrhagic hypotension leads to chemoreceptor anoxia, which consequently results in the reduction of baroreceptor discharge and stimulation of the chemoreceptor. OBJECTIVE: Using the single-unit recording technique, the neuronal activities of the cuneiform nucleus were investigated in hypotensive states induced by hemorrhage and administration of an anti-hypertensive drug (hydralazine). METHODS: Thirty male rats were divided into the control, hemorrhage, and hydralazine groups. The femoral artery was cannulated for the recording of cardiovascular responses, including systolic blood pressure, mean arterial pressure, and heart rate. Hydralazine was administered via tail vein. The single-unit recording was performed from the cuneiform nucleus. RESULTS: The maximal systolic blood pressure and the mean arterial pressure significantly decreased and heart rate significantly increased after the application of hydralazine as well as the following hemorrhage compared to the control group. Hypotension significantly increased the firing rate of the cuneiform nucleus in both the hemorrhage and hydralazine groups compared to the control group. CONCLUSIONS: The present data indicate that the cuneiform nucleus activities following hypotension may play a crucial role in blood vessels and vasomotor tone.

The alteration of neuronal activities of the cuneiform nucleus in non-hypovolemic and hypovolemic hypotensive conditions / Alterações da atividade neuronal no núcleo cuneiforme em condições hipovolêmicas e não hipovolêmicas

Abstract Background: The cuneiform nucleus is located in the center of the circuit that mediates autonomic responses to stress. Hemorrhagic hypotension leads to chemoreceptor anoxia, which consequently results in the reduction of baroreceptor discharge and stimulation of the chemoreceptor. Objective: Using the single-unit recording technique, the neuronal activities of the cuneiform nucleus were investigated in hypotensive states induced by hemorrhage and administration of an anti-hypertensive drug (hydralazine). Methods: Thirty male rats were divided into the control, hemorrhage, and hydralazine groups. The femoral artery was cannulated for the recording of cardiovascular responses, including systolic blood pressure, mean arterial pressure, and heart rate. Hydralazine was administered via tail vein. The single-unit recording was performed from the cuneiform nucleus. Results: The maximal systolic blood pressure and the mean arterial pressure significantly decreased and heart rate significantly increased after the application of hydralazine as well as the following hemorrhage compared to the control group. Hypotension significantly increased the firing rate of the cuneiform nucleus in both the hemorrhage and hydralazine groups compared to the control group. Conclusions: The present data indicate that the cuneiform nucleus activities following hypotension may play a crucial role in blood vessels and vasomotor tone.

RESUMO Antecedentes: O núcleo cuneiforme está localizado no centro do circuito que media as respostas autonômicas ao estresse. A hipotensão hemorrágica leva à anóxia dos quimiorreceptores, que, consequentemente, resulta na redução da descarga dos barorreceptores e estimulação do quimiorreceptor. Objetivo: Utilizando a técnica de registro em unidade única, as atividades neuronais do núcleo cuneiforme foram investigadas em estados de hipotensão induzida por hemorragia e administração de um anti-hipertensivo (hidralazina). Métodos: Trinta ratos machos foram divididos nos grupos controle, hemorragia e hidralazina. A artéria femoral foi canulada, para o registro de respostas cardiovasculares, incluindo pressão arterial sistólica, pressão arterial média e frequência cardíaca. A hidralazina foi administrada na veia da cauda. O registro de unidade única foi realizado a partir do núcleo cuneiforme. Resultados: A pressão arterial sistólica máxima e a pressão arterial média diminuíram significativamente, e a frequência cardíaca aumentou significativamente após a aplicação de hidralazina, bem como a hemorragia seguinte, em comparação com o grupo controle. A hipotensão aumentou significativamente a taxa de disparo da população do núcleo cuneiforme em ambos os grupos de hemorragia e hidralazina, em comparação com o grupo de controle. Conclusões: Os presentes dados indicam que as atividades do núcleo cuneiforme após hipotensão podem desempenhar um papel crucial nos vasos sanguíneos e no tônus vasomotor.

Combination effect of exercise and environmental enrichment on cognitive functions and hippocampal neurogenesis markers of rat.

OBJECTIVES: Cognitive decline is one of the most prevalent health problems and is associated with increased healthcare utilization and economic burden. Physical and cognitive training both have positive effects on cognition but have been less applied in combination. We hypothesized that simultaneous cognitive-physical components would yield greater cognitive benefits than single-domain interventions in rats. METHODS: A total of 40 male Wistar rats were divided into four treatment groups: the control, enriched environment (EE), exercise (EX), and EE + EX. Animals in EE groups housed in the large cages (50 × 50 × 50 cm) contained differently shaped objects for 3 weeks. EX animals were forced to run on a treadmill once daily for 3 consecutive weeks. Morris water maze test was used for the assessment of spatial learning and memory. Real-time PCR was performed to assess the expression of nestin, and Sox2 in the hippocampus. RESULTS: EX and EE animals separately did not show a significantly enhanced function in spatial memory in comparison with the control group. When animals were treated with EE and EX simultaneously, they exhibited significantly superior performance in spatial memory than control, EX, or EE groups separately. The hippocampal expression of Sox2 was significantly higher in EE + EX group than in the control, EX, and EE alone. CONCLUSIONS: These results may have clinical implications for behavioral interventions in conditions with cognitive deficiencies.

Levetiracetam promoted rat embryonic neurogenesis via NMDA receptor-mediated mechanism in vitro.

AIMS: Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with neuroprotective properties and novel mechanisms of action. Some evidence suggests that LEV may impact adult neurogenesis, but the results are controversial. The present study was aimed to evaluate the effects of LEV on the proliferation and differentiation of rat embryonic neural stem cells (NSCs) and to explore the role of GABAB or NMDA receptors. MAIN METHODS: NSCs were isolated from rat fetal ganglionic eminence at embryonic day 14.5. The effects of LEV on viability, proliferation, neurosphere formation, and neuronal or astroglial differentiation of NSCs were assessed using resazurin, BrdU incorporation, immunocytochemistry, quantitative real-time PCR, and western blotting. Additionally, we addressed the relationship between treatment with NMDA and GABAB receptor antagonists (MK801 and saclofen, respectively) in combination with LEV on these parameters. KEY FINDINGS: The data showed that LEV (50 µM) significantly increased the number (p < 0.01) and diameter of neurospheres (p < 0.05), enhanced proliferation (p < 0.01), and promoted neuronal differentiation, as revealed by significantly increased expressions of DCX and NeuN. The expressions of astroglial markers, GFAP and Olig2, were markedly reduced. The addition of MK801 (10 µM) significantly diminished neurospheres growth (p < 0.001), decreased the number of proliferating cells (p < 0.01), and reduced the number of new neurons (p < 0.001) but increased the astroglial cells (p < 0.001) induced by LEV. Co-treatment with saclofen (25 µM) did not significantly affect LEV-induced NSCs proliferation and differentiation. SIGNIFICANCE: Our findings suggest that LEV may enhance rat embryonic neurogenesis mainly through an NMDA receptor-mediated mechanism.

The next step of neurogenesis in the context of Alzheimer's disease.

Among different pathological mechanisms, neuronal loss and neurogenesis impairment in the hippocampus play important roles in cognitive decline in Alzheimer's disease (AD). AD is a progressive and complex neurodegenerative diseases, which is very debilitating. The purpose of this paper is to review recent research into neurogenesis and AD and discuss how pharmacological drugs and herbal active components have impacts on neurogenesis and consequently improve cognitive functions. To date, despite huge research, no effective treatment has been approved for AD. Therefore, an avenue for future research and drug discovery is stimulating adult hippocampal neurogenesis (AHN). Evidence suggests that neurogenesis is regulated by the pharmacological treatment that may be recommended as a part of prophylaxis and therapeutic options for AD. However, the underlying mechanisms of regulating neurogenesis in AD are not well understood. To this point, we highlight to achieve an efficient treatment in AD by manipulating neurogenesis, it's necessary to target all steps of neurogenesis.

Pain-relieving effects of Lawsonia inermis on neuropathic pain induced by chronic constriction injury.

The aim of this study was to determine the role of Lawsonia inermis (L. inermis) extract in the chronic constriction injury (CCI)-induced neuropathic pain. Following CCI surgery, L. inermis extract (250 mg/kg and 500 mg/kg) and gabapentin (100 mg/kg) were administered intraperitoneally for 14 consecutive days. Heat hyperalgesia and allodynia were assessed by radiant heat, aceton drop, and von frey filament tests, respectively. Rat pain behaviors were evaluated on -1sh, 3rd, 5th, 7th, 10th and 14th days post CCI surgery. At the end of the study, the spinal levels of malondialdehyde (MDA), total thiol, IL1-ß, and TNF-α were estimated. Treatment of L. inermis extract reversed the decreased level of thiol and the elevation of MDA level in the spinal cord of CCI rats. Besides, L. inermis extract treatment decreased the elevation of inflammatory markers including IL1-ß, and TNF-α in the spinal cord of CCI rats. These results indicated that L. inermis has potential neuroprotective effects against CCI induced neuropathic pain due to its anti-oxidant, and anti-inflammatory effects.

The Potential Role of Green Tea and its Main Constituent (Epigallocatechin -3-Gallate) in Pain Relief: A Mechanistic Review.

Medicinal plants and dietary supplements may provide an effective and safe treatment for pain relief. Green tea is one of the most common beverages with many several pharmacological activities. The results of various studies have indicated that green tea possesses antinociceptive effects. Many of the protective effects of green tea in terms of pain relief are attributed to its antioxidant and anti-inflammatory properties. Epigallocatechin -3-gallate (EGCG), as one of the major phytochemical components in green tea, is effective in the management of pain through suppression of inflammation and oxidative stress. We have reviewed the effects of green tea on pain and also discussed mechanisms involved in pain relief. This review suggests that green tea can be a safe and often effective treatment for pain.

COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review.

Coronavirus disease 2019 (COVID-19) was reported at the end of 2019 in China for the first time and has rapidly spread throughout the world as a pandemic. Since COVID-19 causes mild to severe acute respiratory syndrome, most studies in this field have only focused on different aspects of pathogenesis in the respiratory system. However, evidence suggests that COVID-19 may affect the central nervous system (CNS). Given the outbreak of COVID-19, it seems necessary to perform investigations on the possible neurological complications in patients who suffered from COVID-19. Here, we reviewed the evidence of the neuroinvasive potential of coronaviruses and discussed the possible pathogenic processes in CNS infection by COVID-19 to provide a precise insight for future studies.

Sex differences in sleep and sleep loss-induced cognitive deficits: The influence of gonadal hormones.

Males and females can respond differentially to the same environmental stimuli and experimental conditions. Chronic sleep loss is a frequent and growing problem in many modern societies and has a broad variety of negative outcomes for health and well-being. While much has been done to explore the deleterious effects of sleep deprivation (SD) on cognition in both human and animal studies over the last few decades, very little attention has been paid to the part played by sex differences and gonadal steroids in respect of changes in cognitive functions caused by sleep loss. The effects of gonadal hormones on sleep regulation and cognitive performances are well established. Reduced gonadal function in menopausal women and elderly men is associated with sleep disturbances and cognitive decline as well as dementia, which suggests that sex steroids play a key role in modulating these conditions. Finding out whether there are sex differences in respect of the effect of insufficient sleep on cognition, and how neuroendocrine mediators influence cognitive impairment induced by SD could provide valuable insights into the best therapies for each sex. In this review, we aim to highlight the involvement of sex differences and gonadal hormone status on the severity of cognitive deficits induced by sleep deficiency in both human and animal studies.

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.

Survival, proliferation, and migration of human meningioma stem-like cells in a nanopeptide scaffold.

OBJECTIVES: In order to grow cells in a three-dimensional (3D) microenvironment, self-assembling peptides, such as PuraMatrix, have emerged with potential to mimic the extracellular matrix. The aim of the present study was to investigate the influence of the self-assembling peptide on the morphology, survival, proliferation rate, migration potential, and differentiation of human meningioma stem-like cells (hMgSCs). MATERIALS AND METHODS: The efficacy of a novel method for placing hMgSCs in PuraMatrix (the injection approach) was compared to the encapsulation and surface plating methods. In addition, we designed a new method for measurement of migration distance in 3D cultivation of hMgSCs in PuraMatrix. RESULTS: Our results revealed that hMgSCs have the ability to form spheres in stem cell culture condition. These meningioma cells expressed GFAP, CD133, vimentin, and nestin. Using the injection method, a higher proliferation rate of the hMgSCs was observed after seven days of culture. Furthermore, the novel migration assay was able to measure the migration of a single cell alone in 3D environment. CONCLUSION: The results indicate the injection method as an efficient technique for culturing hMgSCs in PuraMatrix. Furthermore, the novel migration assay enables us to evaluate the migration of hMgSCs.