Oxidative stress and neuroinflammation are the main contributors to Alzheimer's disease (AD). The current study evaluated the neuroprotective efficacy of 3-(2,4- dimethylbenzylidene)-6-chloroindolin-2-one (DMO) against D-Galactose (GAL)-induced neuroinflammation, oxidative stress, and memory impairment in mice. Swiss Male albino mice weighing (25-30 g) were assigned to five experimental groups (n=6) (i) Normal group (received normal saline 0.9%) (ii) Control group (received GAL 100 mg/kg i.p) (iii) Standard group (received Donepezil 5 mg/kg + GAL 100 mg/kg i.p) (iv) Treatment group 1 (received DMO 5 mg/kg + GAL 100 mg/kg i.p) and Treatment group 2 (received DMO 10 mg/kg + GAL 100 mg/kg i.p) once daily for 8 weeks. After treatment, the mice were subjected to behavioral analysis, followed by sacrifice for further analysis. DMO alleviated GAL-induced cognitive impairment as shown by the Morris water maze test (MWM), Y-maze, elevated plus maze (EPM), and open field (OF) test. Brain tissue histology showed reversal of distorted neuronal structures and decreased pyknosis upon DMO treatment. DMO also decreased the levels of Glutathione-S-Transferase (GST), reduced Glutathione (GSH), and catalase (CAT), concomitant with increased lipid peroxidase (LPO). Furthermore, levels of TNF-α and NF- ҡB, were significantly reduced in the DMO treatment groups as quantified by ELISA. In addition, Reverse transcription polymerase chain reaction (RT-PCR) showed a substantial decrease in the expression of β-amyloid and Tau protein. The results showed that DMO inhibits D-gal induced oxidative stress, neuroinflammation and consequently alleviates memory impairment. Our novel findings suggest that DMO could be a promising therapeutic modality for the treatment of brain aging-associated disorders.

Paclitaxel is a widely used chemotherapeutic agent, but its administration is frequently ac-companied by neuropathic pain and cognitive impairment, which together profoundly diminish the quality of life in cancer patients. Unfortunately, existing therapeutic strategies for PTX-induced ab-normalities remain inadequate, with limited efficacy and significant adverse effects. Central to the per-ception of pain and the regulation of cognitive function is the Anterior Cingulate Cortex (ACC). The integrative role of the ACC depends on tightly regulated neuronal activity, neurotransmitter homeosta-sis, and neuroplasticity-defined as the ability of the brain to reorganize and form new neural connec-tions-all of which may be disrupted by PTX. Electroacupuncture (EA), a non-pharmacological inter-vention with an excellent safety profile, has emerged as a promising therapy capable of relieving pain and ameliorating cognitive impairment in this context. This review first outlines the pathophysiological mechanisms of PTX-induced pain and cognitive dysfunction, including both peripheral neurotoxicity and central sensitization-a heightened response of the central nervous system to stimulation. It then de-tails the neuroanatomical and functional contributions of the ACC to these processes, with special em-phasis on its influence over memory and attention. Subsequently, the article discusses the mechanisms by which EA mitigates PTX-induced symptoms, including its regulatory effects on neurotransmitter systems, modulation of microglial activity, and promotion of neuroplasticity-particularly within the ACC. The synergy between EA and other therapeutic modalities, such as pharmacological treatments and cognitive rehabilitation, is also addressed. Finally, the need for future research is highlighted, in-cluding the optimization of EA parameters, a deeper exploration of ACC connectivity with other brain regions, and the development of multimodal treatment strategies. In sum, targeting the ACC with EA represents a promising approach for alleviating PTX-induced neuropathic pain and cognitive impair-ment, providing a theoretical foundation by elucidating underlying mechanisms to improve the clinical management of chemotherapy side effects.

Traumatic brain injury presents a significant challenge, characterized by complex pathologies including neuroinflammation and axonal degeneration with limited treatment options. One of the promising areas of traumatic brain injury treatment is cell therapy. However, a critical aspect of this therapy is the method of stem/progenitor cell administration. This study aimed to evaluate the therapeutic potential of glial progenitor cells derived from induced pluripotent stem cells after intra-arterial administration in an experimental model of traumatic brain injury of male Wistar rats. Neurological status was assessed using the limb-placing, cylinder, and beam walking tests. Lesion volume was quantified by magnetic resonance imaging. Markers of inflammation and neurogenesis were analyzed using immunofluorescence staining and quantitative reverse transcription polymerase chain reaction. Cell migration was tracked via magnetic resonance imaging and histology. Intra-arterial administration provided targeted delivery of cells into the cerebral vasculature. The cells successfully crossed the blood-brain barrier, migrated into the brain parenchyma, and were detectable for up to 48 hours. Transplantation led to significant improvement in sensorimotor function, reduced neuroinflammation in the injured area, and promoted neurogenesis. The observed therapeutic effects are likely mediated by the factors secreted by glial progenitor cells, which possess anti-inflammatory and regenerative properties (paracrine signaling effect) and/or by their transient interactions with the target cells (juxtacrine signaling effect). Glial progenitor cells derived from induced pluripotent stem cells and delivered via the intra-arterial route show promise for the treatment of traumatic brain injury by reducing inflammation and enhancing neurogenesis.

The repair mechanisms following sciatic nerve injury involve complex signaling interactions between neurons and microglia. Recent studies have demonstrated that neurons activate microglia by releasing chemokines, glutamate, and neurotrophic factors. In turn, microglia regulate neuronal survival and regeneration via phagocytosis, phenotypic switching, and secretion of growth factors. However, the spatiotemporal diversity of signaling pathways, metabolic regulation of the microenvironment, and barriers to clinical application remain inadequately addressed. This review provides a comprehensive analysis of morphological and functional changes in neuronal cell bodies and of the activation and regulatory mechanisms of microglia after sciatic nerve injury. It highlights the dynamic interaction network encompassing the ATP-P2X7 signaling pathway, the CX3CL1- CX3CR1 pathway, the CCL2-CCR2 chemokine axis, the BDNF-TrkB pathway, and inflammatory mediators, offering novel insights into precision therapeutic strategies targeting neuron-glial interactions.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively declining cognitive abilities and memory impairment. This disease increasingly challenges the quality of life and health of the elderly population, underscoring the need for effective therapeutic strategies. The existing anti-AD medications are designed to improve symptoms but not to cure the disease. Novel drugs are urgently needed to target the specific mechanisms that mediate disease progression. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a potential target for the development of anti-AD therapies. Through virtual screening of natural PPAR-γ ligands, the flavonoid diosmin was found to bind to PPAR-γ with high potency. This study exploited diosmin as a lead compound to design a panel of diosmin analogs via chemical modifications for better biological efficacy in targeting PPAR-γ. These diosmin analogs were evaluated using in silico approaches, including molecular docking, absorption, distribution, metabolism, and excretion (ADME) predictions, and molecular dynamics (MD) simulations. As a result, molecular docking identified 12 di-osmin analogs with better binding affinity to PPAR-γ compared with diosmin. ADME and MD analyses demonstrated that S1DhP1 exhibited lower binding free energy, better water solubility, and stability than diosmin. Thus, this study provides important information via in silico approaches and hypotheses, suggesting S1DhP1 as a promising PPAR-γ agonist for the treatment of AD that warrants further experimental validation.

Neurodegenerative Diseases (NDs) are disorders that cause nerve cells to gradually deteriorate or die. Progressive malfunction and neuronal loss from certain brain areas are hallmarks of neurodegenerative diseases. In various parts of the brain, this results in dementia, cognitive impairment, and a slowdown in motor function. Because pyrazole scaffolds play a significant role in the brain by enhancing cognitive processes, they have drawn a lot of interest for the treatment of neurodegeneration. Pyrazole-containing substances have recently been effectively produced as strong inhibitors of many biological targets implicated in various neurodegenerative disorders. In the present review, initially, we provide an overview of the chemistry of pyrazoles, methods for creating pyrazole derivatives, and the pharmaceutical properties of pyrazole derivatives. We show that, thanks to recent developments in synthetic medicinal chemistry, this class of molecules may be easily synthesized and targeted for novel drug discovery. In particular, the present review focuses on the neuroprotective properties of pyrazole scaffolds, given pyrazoles' importance in medicinal chemistry as neuroprotective agents. We have made an effort to examine several facets of the therapeutic potential of pyrazole analogues as anti-neurodegenerative agents in this review. The purpose of this study is to help medicinal chemists and neuroscientists who are investigating and using pyrazoles in neurodegenerative research projects, as well as to expedite future research initiatives in neurodegenerative disease. Future studies and fresh ideas in the search for logical designs to create more promising pyrazoles are anticipated to benefit from this review.

Neurodegenerative Disorders (NDDs), including Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and other less prevalent conditions, represent a growing challenge in medical science due to their progressive nature and the absence of curative treatments. Cruciferous vegetables, such as those from the Brassicaceae family and other species in the Brassicales order, have been reported to offer potential benefits for treating and preventing NDDs. Their neuroprotective effects have been attributed to secondary metabolites, glucosinolates (GLs), and their hydrolytic products, isothiocyanates (ITCs). One of these ITCs is Erucin (ERU), chemically known as 4-isothiocyanatobutane, which is a specific type of ITC. ERU is the isothiocyanate derivative of erucic acid and is structurally related to sulforaphane (SFN), another well-known ITC. This review aims to synthesize current scientific knowledge on ERU's mechanisms of action in neurodegeneration, highlighting preclinical evidence supporting its neuroprotective effects in diseases such as AD and PD, and suggesting its potential as a treatment strategy for NDDs. Preliminary studies suggest that ERU may confer neuroprotection through antioxidative stress pathways, modulation of neuroinflammatory responses, and upregulation of neurotrophic factors. This article discusses ERU's chemical properties, pharmacokinetics, and observed impacts on neurodegenerative models, suggesting potential therapeutic pathways it may influence, thereby highlighting its promise as a future component of neuroprotective strategies against NDDs.

This propensity score-matched study utilized data from the MSBase registry to compare outcomes between patients discontinuing OCR due to safety concerns ("Switchers") and those continuing treatment ("Continuers"). Matching was performed using inverse probability of treatment weighting (IPTW) to balance treatment duration and baseline characteristics. Primary outcomes included annualized relapse rate (ARR), time to first relapse, 24-48 weeks confirmed disability worsening (CDW), and progression independent of relapse activity (PIRA). From an initial cohort of 310 Switchers and 1,315 Continuers, 66 patients who experienced at least one safety event and switched from OCR were matched with 66 Continuers. PS-IPTW analyses revealed higher ARR in Switchers (0.08, 95% CI: 0.05-0.14) versus Continuers (0.038, 95% CI: 0.02-0.07; p=0.040). Time to first relapse showed no significant difference (HR=2.23, 95% CI: 0.68-7.28; p=0.183). Trends toward increased CDW24 weeks risk (PS-IPTW HR=2.11, 95% CI: 0.93-4.75; p=0.073), while no significant difference was found at 48 weeks (HR=1.81, 95% CI: 0.83-3.30; p=0.201). PIRA risk showed a trend toward an increase in Switchers (HR=2.45, 95% CI: 0.95-6.29; p=0.063). In this propensity-score-matched analysis, OCR discontinuation due to safety concerns was associated with increased relapse activity and trends toward greater disability progression. These findings highlight the importance of maintaining therapeutic intensity and systematic monitoring during treatment transitions to mitigate safety risks Conclusion: Further research is needed to develop strategies for effectively managing adverse events to optimize patient outcomes.

Pharmacological treatments for Post-Traumatic Stress Disorder (PTSD), a disorder that affects emotions and mental health and is thought to be therapeutically deficient, either appear to have a number of adverse effects or cause patients to not take their medications as directed. The effectiveness of non-pharmacological treatments for PTSD-related anxiety, depression, and trauma-related discomfort is examined in the current systematic review. Fifty-five relevant studies that reported on the randomized controlled trials and metaanalyses published between 2008 and 2025 were found through a thorough search of a total of 12 databases. Mindfulness-Based Stress Reduction (MBSR), Cognitive Behavioral Therapy (CBT), Eye Movement Desensitization and Reprocessing (EMDR), laughter therapy, acupuncture, dietary modifications, and yoga are among the interventions of interest that were studied. The severity of PTSD symptoms has been reported to be reliably reduced by MBSR, CBT, and EMDR; some trials of MBSR and CBT have shown improvements of up to 45%. Acupuncture, yoga, and laughter therapy all demonstrated positive impacts; the outcomes varied significantly. Dietary and lifestyle changes appeared to help stabilize mental health, but further research is needed. Results highlight the benefits of non-pharmacological therapies as highly effective and preferable PTSD treatment options, especially for individuals who are sensitive to pharmacotherapy. The strongest, most reliable results were obtained by MBSR and CBT in particular, highlighting the significance of cognitive restructuring and present-moment concentration. While nutrition, yoga, acupuncture, and laughter therapy all contributed to stress alleviation or emotional regulation, EMDR was particularly effective at processing memories without the requirement for verbalization. These tactics encourage resilience, self-control, and empowerment, but future research must address methodological variation, sample size, and intervention standardization. Non-pharmacological approaches offer promising complementary or standalone strategies for PTSD management. Further large-scale, standardized trials are warranted to strengthen the evidence base and optimize treatment protocols.

Introduction: Ischemic stroke (IS) is a major global health challenge, associated with high mortality and long-term disability. Current treatment strategies, including pharmacotherapy and acute reperfusion therapy, have significant limitations, underscoring the urgent need for novel neuroprotective agents. Andrographolide (AG), a bioactive compound derived from Andrographis paniculata, has demonstrated potent neuroprotective effects in various neurological disorders; however, the precise mechanisms underlying its efficacy in IS remain incompletely understood. This review aims to provide a comprehensive summary of the pharmacological effects of AG in IS, with the goal of identifying potential therapeutic avenues. Methods: A systematic literature search was conducted using PubMed, ScienceDirect, Web of Science, and Google Scholar, focusing on in vitro and in vivo studies that evaluated AG as a neuroprotective agent in the context of IS. Results: IS is a complex disease resulting from cerebral ischemia, which disrupts neural networks and triggers pathological processes including inflammation, blood-brain barrier (BBB) injury, and cell death. AG exhibits neuroprotective properties through multiple mechanisms, including antiinflammatory activity, endothelial cell protection, anti-apoptotic effects, and inhibition of platelet aggregation. Conclusion: AG represents a promising neuroprotective candidate for IS, acting via diverse mechanisms and pathways. Further research is warranted to elucidate its molecular targets and to explore its clinical potential in IS therapy.