Primary angle-closure glaucoma (PACG) has traditionally been regarded as an ocular disorder, but accumulating evidence suggests broader central nervous system involvement. Although previous neuroimaging studies have identified static functional abnormalities, the dynamic properties of large-scale brain networks and their associated molecular signatures in PACG remain insufficiently understood. We applied Leading Eigenvector Dynamics Analysis to resting-state functional MRI data from 44 patients with PACG and 57 healthy controls to characterize recurrent whole-brain dynamic states. State-specific temporal metrics and spatial patterns were further evaluated using multiple machine learning models. To explore potential biological correlates, imaging-derived spatial patterns were linked to cortical gene expression profiles from the Allen Human Brain Atlas using partial least squares regression, followed by pathway enrichment, cell-type enrichment, and neurotransmitter receptor/transporter mapping analyses. Compared with healthy controls, PACG patients showed prolonged dwell time in one recurrent dynamic state, suggesting reduced flexibility of large-scale brain dynamics. Machine learning models showed promising classification performance within the current dataset, with the most informative features primarily located in default mode network regions. Transcriptomic decoding revealed enrichment of genes related to synaptic signaling, ion channel activity, neurotransmitter transport, and neuronal communication. Cell-type enrichment analyses further implicated excitatory neurons, inhibitory neurons, and astrocytes. In addition, a significant spatial association with VMAT2 suggested that monoaminergic systems may be relevant to the observed imaging phenotype. PACG is associated with altered large-scale brain dynamics, particularly involving default mode network-related state instability. These imaging abnormalities show spatial associations with molecular, cellular, and neurotransmitter-related signatures.

Outcomes and prognostic factors of hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and central nervous system involvement.

Recent advances in self-assembled nanoplatforms for central nervous system disorders therapy: Design principles, multifunctional strategies, and therapeutic applications.

Effective treatment of viral infections in the central nervous system (CNS) requires adequate nucleoside analogs exposure and conversion into phosphorylated metabolites (TP) in brain cells. To develop a CNS PBPK model (LeiCNS-PK3.2) that incorporates active brain cell membrane transport and brain intracellular fluid (brainICF) metabolism to predict and understand target site pharmacokinetics (PK), brainICF active triphosphate (TP) metabolites, and effects of antiviral drugs. LeiCNS-PK3.0 was extended with a brain cell membrane asymmetry factor (AF) using rat-derived Kp,uu,cell values. Intracellular conversion of acyclovir and ganciclovir into TPs was modelled using in vitro kinetic parameters. LeiCNS-PK3.2 was validated on published rat and human plasma, brain extracellular fluid (brainECF), and cerebrospinal fluid (CSF) data. Simulated PK profiles for parent drug standard dosing regimens (acyclovir 10 mg/kg t.i.d.; ganciclovir 5 mg/kg b.i.d.) were compared to parent-drug profiles in brainECF, and TP metabolite in brainICF. Sensitivity analyses were performed on CNS physiological parameters and Kp,uu,cell values. LeiCNS-PK3.2 accurately recaptured the observed data (<2-fold error range). Simulated brainECF parent drug concentrations often remained below reported IC50 values, whereas brainICF TPs had smaller AUCs and longer time to equilibrium compared to acyclovir/ganciclovir in brainECF. Simulated pathological variations during CNS infection showed minimal impact on brainICF TP exposure, with proportional shifts in brainICF TP concentrations when varying Kp,uu,cell. CONCLUSIONS: LeiCNS-PK3.2 can predict CNS target-site exposure of TPs and demonstrates that brainECF acyclovir/ganciclovir concentrations are distinct from brainICF TP levels. It may support intracellular PK/PD target determination to optimize dosing strategies for CNS viral infections.

Flatfish metamorphosis is an abrupt post-embryonic transformation driven by thyroid hormones (THs), in which a bilaterally symmetric pelagic larvae becomes an asymmetric benthic juvenile. While the craniofacial changes associated with eye migration during metamorphosis are well documented, the role of THs in central nervous system (CNS) remodelling remains poorly understood. Here we investigated the role of THs on CNS remodelling during metamorphosis of the flatfish, Solea senegalensis, by integrating high-throughput transcriptomic analysis with experimental manipulation of TH availability using an inhibitor of hormone synthesis, methimazole (MMI) or exogenous T4. Transcriptome profiling revealed 567 differentially expressed gene transcripts associated with TH-levels involved in CNS development, neuronal and glial differentiation, migration, myelination and metabolism. Key CNS-related factors such as klf9, sox9, mbp, and plp were strongly down-regulated in MMI-treated larvae. Cell proliferation assays further demonstrated increased interocular neural proliferation under hypothyroidism, consistent with impaired differentiation. Region-specific analyses of the head and body uncovered distinct patterns of TH signalling involving dio2, dio3, thra, thrb, and mct8, underscoring the spatial complexity of endocrine regulation. These results highlight that THs are crucial for both morphological remodelling and CNS plasticity during flatfish metamorphosis, underscoring their conserved role in vertebrate brain development.

Candida infections of the central nervous system (CNS) with intracranial shunts are difficult to treat. Cultures of cerebrospinal fluid (CSF) may lack sensitivity in detecting deep cerebral candidiasis. The fungal biomarker (1→3)-β-D-glucan (BDG) in CSF and serum was used to assess therapeutic response in a child with device-associated recurrent infection from Candida metapsilosis . High-dose micafungin was used as the backbone of antifungal therapy. Antifungal therapy guided by resolution of elevated CSF and serum BDG provided the assurance of eradication of C. metapsilosis from CNS and peripheral tissues that permitted the insertion of a replacement ventriculoatrial shunt. Following placement of the ventriculoatrial shunt, there was no recurrence of CNS candidiasis. Serial monitoring of BDG of CSF and serum allowed an individualized approach for intracranial shunt reimplantation. The child remained free of Candida CNS infection for 19 months before his death of unrelated causes.

Exosomes, a specialized class of extracellular vesicles, exhibit significant therapeutic potentials for neurological disorders, in particular for vascular dementia (VaD). VaD is the second most common form of dementia, characterized by cognitive and behavioral impairments. VaD is often linked to hippocampal damage resulting from its vulnerable vascular structure, which disrupts memory formation and retrieval. Secreted by various cell types within the central nervous system, exosomes mediate intercellular communication by transporting bioactive molecules. Growing evidence indicates that exosomes enhance synaptic plasticity, modulate neuroinflammation, inhibit apoptosis, and promote angiogenesis, supporting their therapeutic potentials in VaD. Given the urgent need for effective treatments and the unique ability of exosomes to cross the blood-brain barrier (BBB) and deliver multi-targeted therapies, research in this field is critically important. It offers a viable pathway toward the development of disease-modifying interventions for a condition that is currently managed primarily through symptomatic treatment. This review summarizes current knowledge on the functions of exosomes in the central nervous system, explores recent advances in exosome-based strategies for VaD, and discusses ongoing challenges and future directions for their clinical translation.

Chrono-neuro-nanocarriers: Synchronizing circadian rhythms and glymphatic flow for targeted brain drug delivery

Comparative analysis of static and dynamic postural balance control in multiple system atrophy and Parkinson's disease using an intermittent control model.

Mitofusin 2 in central nervous system disorders: Roles in mitochondrial dynamics and therapeutic Implications.

Clinician perspectives on the clinical utility of Belay Summit™ 2.0 cerebrospinal fluid test - A mixed methods study.

Changes in the complement system are involved in synaptic pruning in major depressive disorder.

While multiple sclerosis (MS) is traditionally regarded as restricted to the central nervous system (CNS), an involvement of the peripheral nervous system (PNS) has been previously detected by histopathology and magnetic resonance neurography (MRN). In the CNS, magnetization transfer contrast (MTC) imaging correlates with areas of demyelination in MS. Here, we aim to characterize and quantify peripheral nerve involvement in patients with relapsing-remitting MS (RRMS) by MTC imaging in correlation with demographic, clinical, and electrophysiologic data. Sixty RRMS patients and 60 age- and sex-matched healthy controls prospectively underwent MTC imaging in a 3.0 Tesla MR scanner. Two axial three-dimensional gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were conducted at the right mid- to distal thigh. Sciatic nerve regions of interest were manually delineated on ten consecutive axial slices with subsequent evaluation of the magnetization transfer ratio (MTR) of the sciatic nerve. Detailed neurologic and electrophysiologic examinations were conducted in all RRMS patients. Sciatic nerve MTR was lower in RRMS patients (27.2±0.5%) than in controls (29.5±0.4%; p=0.0002) and inversely correlated with the duration of symptoms, the expanded disability status scale, and the distal motor latency of the tibial nerve in RRMS patients as well as with age and the body mass index in controls. Sciatic nerve MTR differentiates between RRMS patients and controls and correlates with important clinical and electrophysiologic data suggesting clinical relevance of an MTR decrease in the PNS. Our results provide further evidence of peripheral nerve involvement in RRMS and point towards peripheral co-demyelination.

Effects of supervised progressive resistance training on corticospinal excitability in persons with multiple sclerosis: A randomized controlled trial protocol for the NEXIMS study.

The role of γ-aminobutyric acid and its receptor in metabolic reprogramming and tumor progression.

The role of the gut-spinal axis in immune-metabolic coupling after spinal cord injury.

The African spiny mouse (Acomys dimidiatus) is a unique mammalian model capable of scarless tissue regeneration, extending to the nervous system. Unlike conventional rodents, Acomys show significantly higher levels of adult brain stem cells, enhanced functional plasticity after brain injury, and the ability to regenerate and regain function following severe spinal cord damage. While the regenerative capacity of the Acomys central nervous system (CNS) is only beginning to be explored, existing studies have already challenged the long-standing dogma that adult mammals are incapable of CNS recovery after injury. This review provides a critical overview on the current knowledge of Acomys nervous system biology, from development to repair. We summarize the known cellular and mechanistic insights and highlight the current outstanding questions and research priorities. Understanding how Acomys achieves CNS functional recovery, an ability unmatched by any other known mammal, may ultimately guide strategies to enhance repair in nonregenerative mammals, including humans.

Additive larvicidal activity of albendazole combined with a hydroxyethylamine-derived compound against Toxocara canis larvae: An in vitro and in silico study.

The role of MyD88 in the nervous system: Neuronal functions, implications in neurological diseases, and therapeutic potential.

Lower urinary tract symptoms (LUTS) such as frequency, urgency, and sensation of incomplete emptying are frequently attributed to bladder or urothelial disorders, but pelvic floor myofascial dysfunction is underrecognized as an etiologic factor. To present a conceptual framework for myofascial pelvic floor dysfunction (MPFD) as a contributor to urinary symptoms, review its urologic manifestations, discuss, and explore occult contributing factors, and propose integrated diagnostic and interventional therapeutic strategies. This is a narrative review and conceptual synthesis anchored on recent observational studies and existing literature on myofascial pelvic floor dysfunction. MPFD involves failure of appropriate muscle relaxation (or paradoxical contraction), often resistant to standard rehabilitation if underlying drivers remain untreated. The pelvic floor should be conceptualized as a biomechanical "cuboid" interacting with the diaphragm, spine, and abdominal wall. Patients may present with a spectrum of urinary, bowel, sexual, neurogenic, and pain symptoms. Success in rehabilitation demands identification and targeting occult contributors (anatomic, biomechanical, inflammatory, neurologic, behavioral, and central nervous system). Recognizing and addressing myofascial dysfunction as part of the multidimensional pathophysiology of LUTS may improve outcomes in patients' refractory to bladder-centric therapies. Prospective trials are needed to validate integrative treatment strategies.