Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156222 - 156222
Published: Nov. 9, 2024
Language: Английский
Brain Sciences, Journal Year: 2024, Volume and Issue: 14(1), P. 71 - 71
Published: Jan. 10, 2024
Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, type and number seizures before treatment, well initial unsatisfactory effects medications, are important considerations. Although there several third-generation antiepileptic drugs currently available, their multiple side can negatively affect patient quality life. The inheritance etiology epilepsy complex, involving underlying genetic epigenetic mechanisms. Different neurotransmitters play crucial roles maintaining normal physiology different neurons. Dysregulations neurotransmission, due to transmitter levels changes receptors, result seizures. In this review, we address played by various receptors pathophysiology epilepsy. Furthermore, extensively explore neurological mechanisms involved development progression epilepsy, along its risk factors. highlight new therapeutic targets, pharmacological non-pharmacological strategies employed treatment epileptic syndromes, including drug interventions clinical trials related
Language: Английский
Citations
17
Life, Journal Year: 2024, Volume and Issue: 14(5), P. 582 - 582
Published: April 30, 2024
Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of factors. Clinical studies highlight their therapeutic potential, particularly conditions like postpartum depression (PPD), where FDA-approved compound brexanolone, an intravenous formulation allopregnanolone, effectively suppresses TLR-mediated pathways, predicting symptom improvement. Additionally, pregnane neurosteroids trophic anti-inflammatory properties, stimulating vital proteins Androstane including estrogens androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression activation. Notably, androstenediol (ADIOL), androstane neurosteroid, emerges as a potent agent, promising for interventions. The dysregulation immune responses via signaling alongside reduced levels endogenous significantly contributes to severity across various neuropsychiatric disorders. Neuroactive such demonstrate alleviating symptoms disorders modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes significant steroids addressing processes associated It advances our understanding complex interplay between paving way personalized treatment strategies tailored individual needs providing insights future research aimed at unraveling intricacies
Language: Английский
Citations
9
Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104289 - 104289
Published: Jan. 1, 2025
Increasing evidence from fluid biopsies suggests activation and injury of glial cells in epilepsy. The prevalence clinical subclinical seizures neurodegenerative conditions such as Alzheimer's disease, frontotemporal dementia, others merits review comparison the effects on markers epilepsy diseases with concomitant seizures. Herein, we revisit preclinical reports alterations proteins cerebrospinal blood associated various types We consider shared distinct characteristics changes different age groups sexes, humans animal models epilepsy, compare them those reported biofluids diseases. Our analysis indicates a significant overlap response these prevalent neurological conditions.
Language: Английский
Citations
1
Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases therapeutic responses. Although numerous probes are available pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an 18F-labeled tracer (QTFT) that targets P2Y12, a receptor highly expressed on [18F]QTFT exhibited high binding affinity P2Y12 (14.43 nmol/L) superior blood-brain barrier permeability compared other candidates. Micro-PET in IL-4-induced neuroinflammation models showed higher uptake lesions contralateral normal tissues. Importantly, specific could be blocked QTFT or antagonist. Furthermore, visualized mouse epilepsy, glioma, aging targeting aberrantly pilot clinical successfully located epileptic foci, showing enhanced radioactive signals patient with epilepsy. Collectively, studies suggest serve valuable diagnostic tool disorders overexpressed
Language: Английский
Citations
1
Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 24, 2025
Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought play role in such cases. Despite being long-debated issue the field DRE, mechanisms underlying neuroinflammation have yet be fully elucidated. The pro-inflammatory microenvironment within brain tissue with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells cytokines nervous system can lead extensive biochemical changes, as connexin hemichannel excitability disruption neurotransmitter homeostasis. presence inflammation may give rise neuronal network abnormalities suppress endogenous antiepileptic systems. We focus on anomalies from multiple perspectives identify critical points clinical application. hope provide an insightful overview advance quest better treatments.
Language: Английский
Citations
1
Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105867 - 105867
Published: Aug. 28, 2024
Neurodegenerative diseases (NDDs) are a series of disorders characterized by the progressive loss specific neurons, leading to cognitive and locomotor impairment. NDDs affect millions patients worldwide but lack effective treatments. Dysregulation lipids, particularly accumulation lipid droplets (LDs), is strongly implicated in pathogenesis NDDs. How LDs contribute occurrence development NDDs, their potential as therapeutic targets remain be addressed. In present review, we first introduce processes formation, transportation degradation. We then highlight how contributes cell type-specific manner. Moreover, discuss currently available methods for detecting elaborate on LDs-based strategies Lastly, identify gaps that need filled better leverage LD-based theranostics other diseases. hope this review could shed light role facilitate novel
Language: Английский
Citations
7
Journal of Evolutionary Biochemistry and Physiology, Journal Year: 2024, Volume and Issue: 60(2), P. 672 - 689
Published: March 1, 2024
Language: Английский
Citations
5
Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Sept. 13, 2024
Abstract Background Temporal lobe epilepsy (TLE) is among the most common types of and often leads to cognitive, emotional, psychiatric issues due frequent seizures. A notable pathological change related TLE hippocampal sclerosis (HS), which characterized by neuronal loss, gliosis, an increased neuron fibre density. The mechanisms underlying TLE-HS development remain unclear, but reactive transcriptomic changes in glial cells neurons hippocampus post-epileptogenesis may provide insights. Methods To induce TLE, 200 nl kainic acid (KA) was stereotactically injected into CA1 region mice, followed a 7-day postinjection period. Single-cell RNA sequencing (ScRNA-seq), single-nucleus (SnRNA-seq), Xenium-based spatial transcriptomics analyses were employed evaluate mRNA expression neurons. Results From ScRNA-seq SnRNA-seq data, 31,390 48,221 nuclei identified. Analysis differentially expressed genes (DEGs) revealed significant alterations mice with affecting hundreds thousands mRNAs their signalling pathways. Enrichment analysis indicated activation stress inflammatory pathways hippocampus, while axonal neural support suppressed. Xenium demonstrated all 247 across mouse brain sections, revealing distributions 27 cell types. Integrated DEGs identified via three techniques that Spp1 , Trem2 Cd68 upregulated data; Penk Sorcs3 Plekha2 Tle4 Sipa1l3 downregulated data. Conclusion In this study, high-resolution single-cell atlas established, potential intrinsic driving TLE-associated altered interactions. These findings valuable insights for further exploration HS epileptogenesis.
Language: Английский
Citations
5
Brain Research, Journal Year: 2024, Volume and Issue: 1844, P. 149138 - 149138
Published: Aug. 10, 2024
Cognitive impairment is a prevalent co-morbidity associated with epilepsy. Emerging studies indicate that neuroinflammation could be possible link between epilepsy and its comorbidities, including cognitive impairment. In this context, the roles of glial activation, proinflammatory mediators, neuronal death have been well studied correlated epilepsy-associated in animal studies. While recent reports demonstrated anti-epileptogenic anti-convulsant actions metformin, effect on deficit remains unknown. Therefore, current study investigated metformin treatment neuroinflammation, neurodegeneration, deficits after inducing status epilepticus (SE) lithium-pilocarpine rats. Metformin improved hippocampal-dependent spatial recognition memory Morris water maze Novel object tasks, respectively. Further, attenuated microglial astroglial accompanied by reduced IL-1β, COX-2 NF-ĸβ gene expression. Additionally, conferred neuroprotection inhibiting as assessed Nissl staining transmission electron microscopy. These findings suggest holds promise therapeutic intervention for epilepsy, possibly through modulation activation survival. Further research needed to elucidate precise mechanisms assess long-term
Language: Английский
Citations
4
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114117 - 114117
Published: Jan. 30, 2025
Language: Английский
Citations
0