Minato, E. | bioRxiv Science

bioRxiv2025

Sleep fragmentation drives local, network-specific epileptic activity in human epilepsy

Sleep has complex links with epileptic activity, yet the causal role of sleep instability in driving and modulating pathological discharges in the human brain remains incompletely understood. Here we directly examine this by characterising the fine-scale temporal coupling between experimentally induced sleep arousals and interictal epileptiform discharges (IEDs), using combined stereo-electroencephalography and polysomnography recordings in patients with epilepsy. Sleep arousals triggered rapid IED increases, with effects gated by anatomical region and sleep stage. Increases were confined to neocortical regions and occurred during both non-rapid eye movement stage 2 (N2) and stage 3 (N3) sleep, with a larger effect observed in N2. IED increases did not differ between the seizure-onset zone and surrounding regions. Despite elevating IED counts, arousals did not alter IED spatial propagation, indicating state-dependent enhancement of local cortical excitability without recruitment of broader epileptic networks. These findings establish a causal role for sleep instability in actively driving pathological activity on fine-grained spatiotemporal scales, and highlight sleep stabilisation as a promising therapeutic strategy to reduce epileptic burden and preserve cortical network function.

neuroscience↗

bioRxiv2020

PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade

Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on exhausted T cells during chronic illness. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. We reported that the PD-1/PD-L1 pathway is closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Moreover, we found that blocking antibodies targeting PD-1 and PD-L1 restore T-cell functions and may be used in immunotherapy in cattle and dogs. However, the immunological role of the PD-1/PD-L1 pathway remains unclear for chronic equine diseases, including tumors. In this study, we identified nucleotide sequences of equine PD-1 (EqPD-1) and PD-L1 (EqPD-L1) and investigated the role of anti-bovine PD-L1 monoclonal antibodies (mAbs) against EqPD-L1 using in vitro assays. We also evaluated the expression of PD-L1 in tumor tissues of equine malignant melanoma (EMM). The amino acid sequences of EqPD-1 and EqPD-L1 share a high identity and similarity with homologs from other mammalian species. Two clones of the anti-bovine PD-L1 mAbs recognized EqPD-L1 in flow cytometry, and one of these cross-reactive mAbs blocked the binding of equine PD-1/PD-L1. Importantly, PD-L1 expression was confirmed in EMM tumor tissues by immunohistochemistry. A cultivation assay revealed that PD-L1 blockade enhanced the production of Th1 cytokines in equine immune cells. These results suggest that our anti-PD-L1 mAbs may be useful for investigating the expression and role of the equine PD-1/PD-L1 pathway. Further research is required to discover the immunological role of PD-1/PD-L1 in chronic equine diseases and elucidate a future application in immunotherapy for horse.

immunology↗