Biology subjects

Strzelczyk, A.

Publications and source records attributed to Strzelczyk, A..

3 recordsLinked to original sources

bioRxiv2026

Stroke-induced lipocalin-2-expressing red pulp macrophages reprogram peripheral immunity

Acute ischemic stroke (AIS) induces profound systemic immune alterations that contribute to infection susceptibility. Here, we identify lipocalin-2 (LCN-2) as a rapidly induced and conserved regulator of stroke-associated immunosuppression. Using 3-MACE-Seq, cytokine profiling, and immunofluorescence in C57BL/6J mice subjected to transient middle cerebral artery occlusion (tMCAO), we show that LCN-2 is strongly upregulated in splenic red pulp macrophages (RPMs) within 24 hours and again 7 days post-tMCAO. LCN-2-expressing RPMs form immunological synapses with CD3+ T cells, thereby impacting T cell trafficking. Recombinant LCN-2 directly reprogrammed T cells and monocytes toward hyporesponsive, tolerogenic phenotypes by suppressing inflammatory cytokines, impairing chemotaxis, enhancing phagocytosis, and uncoupling oxidative burst. Human spleens likewise displayed LCN-2-expressing CD68+ RPMs, and LCN-2 preconditioning of monocytes reproduced reduced HLA-DR, CD80, CD206, and ROS with increased uptake of E. coli bioparticles. These findings identify LCN-2 signaling as a central orchestrator of stroke-induced peripheral immunoreprogramming and a potential therapeutic target to mitigate post-stroke immunodepression. SummaryAcute ischemic stroke induces LCN-2 in splenic red pulp macrophages, which reprogram T cells and monocytes toward tolerogenic, hyporesponsive states. Mouse and human data identify LCN-2 as a driver of peripheral immunodepression and a potential target to reduce infection risk. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/733904v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@fb0caforg.highwire.dtl.DTLVardef@1fdcd41org.highwire.dtl.DTLVardef@1ae99b0org.highwire.dtl.DTLVardef@1ec0837_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

immunology↗

bioRxiv2025

Hippocampal network activity changes during early epileptogenesis predict subsequent epilepsy

The circuit mechanisms underlying focal epileptogenesis are, despite of decades of epilepsy research, still incompletely understood. In this study, we aimed to characterize the changes in hippocampal network activity induced by a potentially epileptogenic insult. In rats, long-lasting electrical perforant pathway stimulation leads in a high percentage of animals to the development of temporal lobe epilepsy. However, a subset of animals remains resilient against the stimulation. We monitored alterations of neuronal activity by chronically recording the local field potential (LFP) from the hippocampal dentate gyrus before, during and after the potentially epileptogenic insult. Intriguingly, epilepsy animals identified by subsequent spontaneous epileptic seizures were characterized by a transient increase in the aperiodic exponent suggesting a shift towards a reduced local excitation-to-inhibition (E/I) ratio during the first days after the perforant path stimulation. Furthermore, these animals developed a strong impairment of theta oscillation prevalence and regularity during early epileptogenesis. In contrast, resilient non-epilepsy animals without spontaneous seizures neither showed this modulation in E/I ratio nor a corruption of hippocampal theta activity. In fact, the increase in the aperiodic exponent on the first day after completion of the electrical stimulation paradigm could predict epileptogenesis with very high fidelity (AUC 0.92) and correlated significantly with later seizure rate. This finding opens the opportunity to dissect mechanisms of epileptogenesis and to test the effectiveness of anti-epileptogenesis treatment in very early disease stages by allowing identification of individuals at high risk. Furthermore, it might offer a potential explanation for the frequently observed failure of anti-epileptogenesis drugs boosting GABAergic inhibition.

neuroscience↗

bioRxiv2024

Temporal Lobe Epilepsy is dominated by Region Specific Interictal Cortical Inhibition

Epilepsy is typically characterized by excessive neuronal excitability, manifesting as seizures and interictal epileptiform discharges (IEDs) in the EEG. However, the dynamics of excitation and inhibition (E/I balance) remain poorly understood. Here, we leverage the aperiodic exponent of the EEG power spectrum--a marker indicative of synaptic inhibition--to investigate shifts in E/I balance during antiseizure medication (ASM) tapering in patients with mesial temporal lobe epilepsy (TLE). We analyzed EEG data from 28 TLE patients and 25 controls with non-epileptic episodes (NEE) undergoing presurgical video EEG monitoring. Unexpectedly, TLE patients showed a localized increase in the aperiodic exponent in the ipsilesional temporal lobe during ASM tapering, absent in controls. This inhibition increase correlated with seizure latency and predicted seizure occurrence. Intracranial recordings from 10 TLE patients revealed higher aperiodic exponents in the lateral temporal cortex compared to the hippocampus, suggesting stronger inhibition in the lateral cortex. Notably, hippocampal IEDs triggered transient inhibitory responses in the lateral cortex, accompanied by increased high-frequency activity and disrupted hippocampus-to-lateral connectivity. These findings suggest that TLE likely involves complex inhibitory mechanisms beyond the epileptic focus in the interictal period, with neocortical inhibition potentially containing epileptic activity, and offers a new tool to map epileptic brain regions.

neuroscience↗