Exploration of the white matter bundles connected to the pineal gland: A DTI study.

PURPOSE: Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are reports on the role of this area for brain function by hormone secretion, as well as few reports on its role in brain cognition. However, little knowledge is available on the PG, and in particular on the structural connectivity of this region with the other brain structures. METHODS: Using diffusion-weighted images collected by a 3T MRI scanner, and using a sample of 61 (29 F) mentally and physically healthy young individuals in the age range of 20-30 years old, we tried to extract the white matter bundles connected to the PG. Based on prior knowledge, seven target bundles were suggested to be between the PG body and the PG roots, Pons, Periventricular region, thalamus, caudate, lentiform, suprachiasmatic nuclei, and the supercervical ganglia. RESULTS: Nearly all the target bundles were successfully extracted, with the exception of the lentiform. Rate of identification of the tracts was different, with the bundle between the PG body and roots having the highest identification rate (97%); then it was with the Pons (70%), Periventricular region (57%), SCN (55%), left thalamus (52%), right thalamus (47%), left caudate (27%) and right caudate (22%). CONCLUSION: This study is an attempt to expand our knowledge on the neuroanatomy of the PG, which might help for identifying further roles for it in brain functionality, and also be a help for the treatment of some disorders in the future.

From Editorial Board of Special Issue Entitled "Post-Stroke Rehabilitation".

Diseases affecting the nervous system are diverse [...].

Ethical considerations in telehealth and artificial intelligence for work related musculoskeletal disorders: A scoping review.

BACKGROUND: Artificial Intelligence (AI) refers to the simulation of human intelligence in machines that are programmed to perform tasks that typically require human intelligence. The integration of AI and telehealth applications in healthcare raises ethical concerns such as bias, transparency, data privacy, and accountability for errors. Several studies have assessed this topic, particularly with regard to musculoskeletal disorders, which will be the focus of this manuscript. OBJECTIVE: We will examine key ethical concepts including informed consent, data protection, confidentiality, physician malpractice, liability, and telemedicine regulations. METHODS: Ethical issues pertaining to the topic were explored through a review paper. The primary objective of this scoping review was to map and synthesize the existing literature concerning ethical considerations in telehealth and AI for work-related musculoskeletal disorders. RESULTS: Research demonstrates that medication effectiveness, patient and physician satisfaction, and accessibility costs are higher with telemedicine and AI methods compared to in-person approaches, particularly for work-related musculoskeletal disorders. Therefore, addressing ethical issues, including patient data privacy and security, is crucial in this field. By considering these factors, the adoption of emerging AI and telemedicine applications, especially for work-related musculoskeletal disorders, is likely to increase. CONCLUSION: AI and telemedicine offer significant advantages, particularly in addressing work-related musculoskeletal disorders. However, ethical and legal issues surrounding their practice require standardized rules to ensure equitable access, quality care, sustainable costs, professional liability, patient privacy, data protection, and confidentiality. Further practical research studies are needed to address these considerations more effectively.

Maternal exposure to phenanthrene induces testicular apoptosis and Sertoli cell dysfunction in F1 adult male mice: a histological and molecular study.

Objective: Phenanthrene, a polycyclic aromatic hydrocarbon, is found in abundance in environmental pollutants, food, and drinking water. This substance can accumulate in body tissues and exert harmful effects. Moreover, phenanthrene can cross the placental barrier, potentially impacting fetal development. We aimed to explore the impacts of maternal exposure to phenanthrene on testicular tissue and Sertoli cell function in F1 mice. Methods: Female rats with vaginal plugs were randomly assigned to one of three groups: control, sham, or phenanthrene. The control group received no intervention during pregnancy. In the sham and phenanthrene groups, corn oil and a phenanthrene solution, respectively, were administered via gavage once every 2 days. Offspring were separated by sex 21 days after birth. At 56 days postnatal, male F1 offspring were euthanized, and their testes were harvested for histological and molecular analyses. Results: Phenanthrene exposure was associated with a lower testicular weight and volume, a smaller diameter of the seminiferous tubules, and a relative thinning of the germinal epithelium. These changes were associated with increased cellular apoptosis, as shown by the upregulation of caspase 3 expression. Additionally, we observed an increase in vacuolization and residual bodies within the tissue. Conversely, the number of Sertoli cells and expression levels of Sox9, as well as the Ocln and Itgb1 genes, were found to be lowered. Conclusion: Maternal exposure to phenanthrene impacts both germ cells and Sertoli cells, disrupting their function and leading to fertility disorders in male F1 offspring mice.

Inhibition of hippocampal melatonin synthesis by siRNA induced learning and memory deficits in male rats.

Melatonin, the multi-functional neurohormone, is synthesized in the extra-pineal tissues such as the hippocampus. The key enzyme in hippocampal melatonin synthesis is arylalkylamine-N-acetyltransferase (AANAT). The importance of melatonin synthesis in the hippocampus has not yet been determined. We investigated hippocampal AANAT role in cognitive function using gene silencing small interference RNA (siRNA) technology. The hippocampal local melatonin synthesis was inhibited by AANAT-siRNA injection. The time-gene silencing profile of AANAT-siRNA was obtained by RT-PCR technique. The cytotoxicity of siRNA dose was determined by MTT assay on the B65 neural cells. Animals received the selected dosage of AANAT-siRNA. Then, the spatial working memory (Y maze), object recognition memory and spatial reference memory (Morris's water maze, MWM) were evaluated. The anxiety-like behaviors were evaluated by the elevated plus maze. After one week, following the probe test of MWM, the rats were sacrificed for histological analysis. The hippocampal melatonin levels were measured using the liquid chromatography-mass spectrometry technique. The hippocampal melatonin levels in the AANAT-siRNA group decreased. Animals receiving the AANAT-siRNA showed deficits in spatial learning and working memory which were verified by increased escape latency and reduced spontaneous alternations, respectively. There was an increase in anxiety-like behaviors as well as a deficit in recognition memory in the AANAT-siRNA group. The Nissl staining and immunohistochemistry of activated caspase-3 showed the neuronal loss and cell apoptosis in hippocampal tissue of the AANAT-siRNA group. The 18F-FDG-PET imaging displayed lower glucose metabolism following the reduction in AANAT mRNA. Data suggest that the AANAT mRNA and hippocampal melatonin synthesis might be an essential factor for learning, memory and some aspects of cognition, as well as homeostasis of hippocampal cells.

Acellular spinal cord scaffold containing quercetin-encapsulated nanoparticles plays an anti-inflammatory role in functional recovery from spinal cord injury in rats.

Inflammatory responses play a crucial role in the pathophysiology of spinal cord injury (SCI) and developing new approaches to establish an anti-inflammatory environment for the promotion of neuroregeneration holds promise as a potential approach. In this study, our aim was to investigate the potential of combining an acellular spinal cord scaffold (ASCS) with quercetin-loaded bovine serum albumin (Qu/BSA) nanoparticles (NPs) for the treatment of SCI. The ASCS was prepared using physical and chemical methods, while the Qu/BSA NPs were prepared through a desolvation technique. The NPs exhibited favorable characteristics, including a mean size of 203 nm, a zeta potential of -38, and an encapsulation efficiency of 96%. Microscopic evaluation confirmed the successful distribution of NPs on the walls of ASCS. Animal studies revealed that Qu/BSA NPs group exhibited a significant decrease in NLRP3, ASC, and Casp1 gene expression compared to the SCI group (p < 0.0001). The findings indicated a significant decrease in the NLRP3, ASC, and Casp1 protein level between the Qu/BSA/ASCS group and the SCI group (p < 0.0001). Moreover, treatment with ASCS containing either blank BSA (B/BSA) NPs or Qu/BSA NPs effectively promoted functional recovery via increasing the amount of nestin- and glial fibrillary acidic protein (GFAP)-positive cells in the site of injury. Notably, Qu/BSA/ASCS exhibited superior outcomes compared to B/BSA/ASCS. Overall, the combination of ASCS with the Qu delivery system presents a promising therapeutic approach for SCI by inhibiting inflammatory responses and promoting neuroregeneration, leading to the restoration of motor function in animals. This study demonstrates the potential of utilizing biomaterials and NPs to enhance the effectiveness of SCI treatment.

Neurological recovery and neurogenesis by curcumin sustained-release system cross-linked with an acellular spinal cord scaffold in rat spinal cord injury: Targeting NLRP3 inflammasome pathway.

In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.

Neutrophil-to-lymphocyte ratio as a predictive biomarker for early diagnosis of depression: A narrative review.

Depression is a mood disorder that causes persistent feelings of sadness, hopelessness, loss of interest, and decreased energy. Early diagnosis of depression can improve its negative impacts and be effective in its treatment. Previous studies have indicated that inflammation plays an important role in the initiation and development of depression, hence, various inflammatory biomarkers have been investigated for early diagnosis of depression, the most popular of which are blood biomarkers. The Neutrophil to lymphocyte ratio (NLR) may be more informative in the early diagnosis of depression than other widely used markers, such as other leukocyte characteristics or interleukins. Considering the importance of early diagnosis of depression and the role of NLR in early diagnosis of depression, our paper reviews the literature on NLR as a diagnostic biomarker of depression, which may be effective in its treatment. Various studies have shown that elevated NLR is associated with depression, suggesting that NLR may be a valuable, reproducible, easily accessible, and cost-effective method for the evaluation of depression and it may be used in outpatient clinic settings. Closer follow-up can be performed for these patients who have higher NLR levels. However, it seems that further studies on larger samples, taking into account important confounding factors, and assessing them together with other inflammatory markers are necessary to draw some conclusive statements.

Intranasal insulin intake and exercise improve memory function in amyloid-ß induced Alzheimer's-like disease in rats: Involvement of hippocampal BDNF-TrkB receptor.

The most prevalent type of dementia, Alzheimer's disease (AD), is a compelling illustration of the link between cognitive deficits and neurophysiological anomalies. We investigated the possible protective effect of intranasal insulin intake with exercise on amyloid-ß (Aß)-induced neuronal damage. The level of hippocampal brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) were analyzed to understand the involvement of BDNF-TrkB pathway in this modulation. In this study, we induced AD-like pathology by amyloid-ß (Aß) administration. Then, we examined the impact of a 4-week pretreatment of moderate treadmill exercise and intranasal intake of insulin on working and spatial memory in male Wistar rats. We also analyzed the mechanisms of improved memory and anxiety through changes in the protein level of BDNF and TrkB. Results showed that animals received Aß had impaired working memory, increased anxiety which were accompanied by lower protein levels of BDNF and TrkB in the hippocampus. The exercise training and intranasal insulin improved working memory deficits, decreased anxiety, and increased BDNF, and TrkB levels in the hippocampus of animals received Aß. Our finding of improved memory performance after intranasal intake of insulin and exercise may be of significance for the treatment of memory impairments and anxiety-like behavior in AD.

Outcome Measures Utilized to Assess the Efficacy of Telerehabilitation for Post-Stroke Rehabilitation: A Scoping Review.

INTRODUCTION: Outcome measures using telerehabilitation (TR) in the context of post-stroke rehabilitation are an area of emerging research. The current review assesses the literature related to TR for patients requiring post-stroke rehabilitation. The purpose of this study is to survey the outcome measures used in TR studies and to define which parts of the International Organization of Functioning are measured in trials. METHODS: TR studies were searched in Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, Google Scholar, and Web of Science, The Cochrane Central Register of Controlled Trials (Cochrane Library), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Physiotherapy Evidence Database (PEDro) from 2016 to June 2023. Two reviewers individually assessed the full text. Discrepancies regarding inclusion or exclusion were resolved by an additional reviewer. RESULTS: A total of 24 studies were included in the current review. The findings were synthesized and presented taking into account their implications within clinical practice, areas of investigation, and strategic implementation. CONCLUSIONS: The scoping review has recognized a broad range of outcome measures utilized in TR studies, shedding light on gaps in the current literature. Furthermore, this review serves as a valuable resource for researchers and end users (such as clinicians and policymakers), providing insights into the most appropriate outcome measures for TR. There is a lack of studies examining the required follow-up after TR, emphasizing the need for future research in this area.

Magnetogenetic cell activation using endogenous ferritin.

The ability to precisely control the activity of defined cell populations enables studies of their physiological roles and may provide therapeutic applications. While prior studies have shown that magnetic activation of ferritin-tagged ion channels allows cell-specific modulation of cellular activity, the large size of the constructs made the use of adeno-associated virus, AAV, the vector of choice for gene therapy, impractical. In addition, simple means for generating magnetic fields of sufficient strength have been lacking. Toward these ends, we first generated a novel anti-ferritin nanobody that when fused to transient receptor potential cation channel subfamily V member 1, TRPV1, enables direct binding of the channel to endogenous ferritin in mouse and human cells. This smaller construct can be delivered in a single AAV and we validated that it robustly enables magnetically induced cell activation in vitro . In parallel, we developed a simple benchtop electromagnet capable of gating the nanobody-tagged channel in vivo . Finally, we showed that delivering these new constructs by AAV to pancreatic beta cells in combination with the benchtop magnetic field delivery stimulates glucose-stimulated insulin release to improve glucose tolerance in mice in vivo . Together, the novel anti-ferritin nanobody, nanobody-TRPV1 construct and new hardware advance the utility of magnetogenetics in animals and potentially humans.

The Comparative Effects of Schwann Cells and Wharton's Jelly Mesenchymal Stem Cells on the AIM2 Inflammasome Activity in an Experimental Model of Spinal Cord Injury.

Inflammasome activation and the consequent release of pro-inflammatory cytokines play a crucial role in the development of sensory/motor deficits following spinal cord injury (SCI). Immunomodulatory activities are exhibited by Schwann cells (SCs) and Wharton's jelly mesenchymal stem cells (WJ-MSCs). In this study, we aimed to compare the effectiveness of these two cell sources in modulating the absent in melanoma 2 (AIM2) inflammasome complex in rats with SCI. The Basso, Beattie, Bresnahan (BBB) test, Nissl staining, and Luxol fast blue (LFB) staining were performed to evaluate locomotor function, neuronal survival, and myelination, respectively. Real-time polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the gene and protein expressions of inflammasome components, including AIM2, ASC, caspase-1, interleukin-1ß (IL-1ß), and IL-18. Both gene and protein expressions of all evaluated factors were decreased after SC or WJ-MSC treatment, with a more pronounced effect observed in the SCs group (P < 0.05). Additionally, SCs promoted neuronal survival and myelination. Moreover, the administration of 3 × 105 cells resulted in motor recovery improvement in both treatment groups (P < 0.05). Although not statistically significant, these effects were more prominent in the SC-treated animals. In conclusion, SC therapy demonstrated greater efficacy in targeting AIM2 inflammasome activation and the associated inflammatory pathway in SCI experiments compared to WJ-MSCs.

The Effectiveness of Aquatic Therapy on Motor and Social Skill as Well as Executive Function in Children With Neurodevelopmental Disorder: A Systematic Review and Meta-analysis.

OBJECTIVE: To summarize the evidence on the efficacy of aquatic therapy on motor and social skill as well as executive function compared with land-based exercises in children with neurodevelopmental disorders. DATA SOURCES: The following 6 databases were searched: Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, Google scholar (advance), and Web of Science from 1990 to June 2022. STUDY SELECTION: The search included only clinical trials. Two reviewers independently assessed the full text and conducted manuscript selection, data extraction, and quality assessment. DATA EXTRACTION: Using standardized forms, data were extracted and all points of disagreement were discussed between authors. DATA SYNTHESIS: Data synthesis was applied to summarize information from the included trials. The quantitative analysis incorporated fixed-effect models. Of the 150 studies identified in the initial search, 16 trials (248 children) met the eligibility criteria. Aquatic therapy improved factors related to the Humphries' Assessment of Aquatic Readiness (HAAR) checklist such as mental adjustment (standardized mean difference [SMD], 0.69; 95% confidence interval [CI], 0.20-1.19; I2=10%) compared with land-based exercises (control), water environment (SMD, 0.99; 95% CI, 0.43-1.54; I2=83%), Rotation (SMD, 0.63; 95% CI, 0.14-1.12; I2=0%), balance and control (SMD, 2.09; 95% CI, 1.47-2.72; I2=36%) and independent movement (eg, walking, moving upper body, standing, transferring) in water (SMD, 0.87; 95% CI, 0.37-1.38; I2=0%) compared with the control group in the 4 trails. The HAAR tool is based on the Halliwick method and aims to assess the appropriateness for an individual with disability to engage in aquatic therapy. The study protocol was also registered with PROSPERO number CRD42022341898. CONCLUSION: Aquatic therapy demonstrated a more robust positive effect on factors related to the HAAR checklist than land-based exercises. Further research is needed to further elucidate the clinical utility of aquatic therapy for children with neurodevelopmental disorder at long-term follow-up.

Telestroke: A Novel Approach for Post-Stroke Rehabilitation.

Despite the tremendous technologic advancements of recent years, the prevalence of stroke has increased significantly worldwide from 1990 to 2019 (a 70 [...].

Wharton's jelly mesenchymal stem cells attenuate global hypoxia-induced learning and memory impairment via preventing blood-brain barrier breakdown.

Objectives: Intracerebroventricular (ICV) injections of mesenchymal stem cells (MSCs) may improve the function and structure of blood-brain barrier (BBB), possibly by preserving the BBB integrity. This study examined the impact of Wharton's jelly (WJ)-MSCs on cognitive dysfunction and BBB disruption following a protracted hypoxic state. Materials and Methods: Twenty-four male Wistar rats were randomly studied in four groups: Control (Co): Healthy animals, Sham (Sh): Rats were placed in the cage without hypoxia induction and with ICV injection of vehicle, Hypoxic (Hx)+vehicle: Hypoxic rats with ICV injection of vehicle (5 µl of PBS), and Hx+MSCs: Hypoxic rats with ICV injection of MSCs. Spatial learning and memory were evaluated one week after WJ-MSCs injection, and then animals were sacrificed for molecular research. Results: Hypoxia increased latency and lowered the time and distance required reaching the target quarter, according to the findings. Furthermore, hypoxic rats had lower gene expression and protein levels of hippocampus vascular endothelial (VE)-cadherin, claudin 5, and tricellulin gene expression than Co and Sh animals (P<0.05). Finally, administering WJ-MSCs after long-term hypoxia effectively reversed the cognitive deficits and prevented the BBB breakdown via the upregulation of VE-cadherin, claudin 5, and tricellulin genes (P<0.05). Conclusion: These findings suggest that prolonged hypoxia induces spatial learning and memory dysfunction and increases BBB disruption, the potential mechanism of which might be via reducing VE-cadherin, claudin 5, and tricellulin genes. Hence, appropriate treatment with WJ-MSCs could reverse ischemia adverse effects and protect the BBB integrity following prolonged hypoxia.

Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis.

Diabetic neuropathy (DN) is the most prevalent complication of diabetes. Pharmacological treatments for DN are often limited in efficacy, so the development of new agents to alleviate DN is essential. The aim of this study was to evaluate the effects of rolipram, a selective phosphodiesterase-4 inhibitor (PDE-4I), and pentoxifylline, a general PDE inhibitor, using a rat model of DN. In this study, a diabetic rat model was established by i.p. injection of STZ (55 mg/kg). Rats were treated with rolipram (1 mg/kg), pentoxifylline (100 mg/kg), and combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for 5 weeks. After treatments, sensory function was assessed by hot plate test. Then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP, adenosine diphosphate and mitochondrial membrane potential (MMP) levels, Cytochrome c release, Bax, Bcl-2, caspase-3 proteins expression in DRG neurons were assessed by biochemical and ELISA methods, and western blot analysis. DRG neurons were histologically examined using hematoxylin and eosin (H&E) staining method. Rolipram and/or pentoxifylline significantly attenuated sensory dysfunction by modulating nociceptive threshold. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, prevented mitochondrial dysfunction, apoptosis and degeneration of DRG neurons, which appears to be mediated by inducing ATP and MMP, improving cytochrome c release, as well as regulating the expression of Bax, Bcl-2, and caspase-3 proteins, and improving morphological abnormalities of DRG neurons. We found maximum effectiveness with rolipram and pentoxifylline combination on mentioned factors. These findings encourage the use of rolipram and pentoxifylline combination as a novel experimental evidence for further clinical investigations in the treatment of DN.

Mesenchymal stem cells (MSCs) and MSC-derived exosomes in animal models of central nervous system diseases: Targeting the NLRP3 inflammasome.

The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is a multimeric protein complex that is engaged in the innate immune system and plays a vital role in inflammatory reactions. Activation of the NLRP3 inflammasome and subsequent release of proinflammatory cytokines can be triggered by microbial infection or cellular injury. The NLRP3 inflammasome has been implicated in the pathogenesis of many disorders affecting the central nervous system (CNS), ranging from stroke, traumatic brain injury, and spinal cord injury to Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, and depression. Furthermore, emerging evidence has suggested that mesenchymal stem cells (MSCs) and their exosomes may modulate NLRP3 inflammasome activation in a way that might be promising for the therapeutic management of CNS diseases. In the present review, particular focus is placed on highlighting and discussing recent scientific evidence regarding the regulatory effects of MSC-based therapies on the NLRP3 inflammasome activation and their potential to counteract proinflammatory responses and pyroptotic cell death in the CNS, thereby achieving neuroprotective impacts and improvement in behavioral impairments.