Biology subjects

Herr, S.

Publications and source records attributed to Herr, S..

3 recordsLinked to original sources

bioRxiv2025

Electrocorticographic Detection of Speech Networks in Glioma-infiltrated Cortex

Direct cortical stimulation (DCS) is the clinical gold standard for identifying functional cortex in the human brain, which is essential for the safe removal of brain lesions. Defining the electro-physiological properties of DCS- positive cortical regions may facilitate the identification of critical language regions, thereby permitting safe glioma resections in communities without access. Leveraging a multicenter electrophysiologic dataset of DCS- positive language regions spatially matched with subdural arrays, we analyzed regions identified as functionally critical (DCS+) versus functionally non-critical (DCS-) during intraoperative language mapping. In IDH-mutant gliomas, DCS+ regions exhibited significantly greater speech-related neural activity and enhanced encoding and decoding of linguistic and semantic features. We demonstrate that resting-state classifiers distinguish DCS+ from DCS- regions in IDH-mutant tumors. Task-based and resting-state electrophysiologic distinctions were pathology-specific and not present in IDH-wildtype glioblastomas. These findings may accelerate DCS mapping by guiding surgeons to priority regions, improving efficiency, and patient outcomes.

neuroscience↗

bioRxiv2025

The Pathological Role and Therapeutic potential of ALDH2 in acrolein detoxification Following Spinal Cord Injury in Mice

Oxidative stress and lipid peroxidation-derived aldehydes, such as acrolein, play a central role in the pathology of spinal cord injury (SCI) and have emerged as promising therapeutic targets. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is a key oxidoreductase responsible for detoxifying reactive aldehydes. Pharmacological activation of ALDH2 using Alda-1, a selective agonist, has been shown to reduce aldehyde accumulation, alleviate inflammation, and enhance functional recovery in experimental SCI models. However, approximately 8% of the global population carries the ALDH2*2 mutation, which severely impairs this detoxification pathway. In this study, we used a transgenic ALDH2*2 mouse model to investigate the role of ALDH2 in SCI pathology. This model mimics the human ALDH2*2 condition, allowing us to examine the impact of impaired aldehyde clearance on acrolein accumulation and its pathological consequences. We modulated endogenous aldehyde detoxification through both genetic deficiency and pharmacological activation with Alda-1. Our results showed that ALDH2 deficiency led to significantly elevated acrolein levels, which were associated with increased microglial activation, cytokine storm, neuronal loss, demyelination, and tissue damage compared to wild-type (WT) mice. Treatment with Alda-1 enhanced ALDH2 activity and significantly reduced acrolein levels in both ALDH2*2 and WT mice from 2 to 28 days post-SCI. This was accompanied by reduced inflammation, improved preservation of myelin, and marked improvements in locomotor and sensory function, especially in ALDH2*2 mice. Notably, even beyond the traditionally ideal treatment window, Alda-1 treatment remained effective in promoting recovery, particularly in motor function and to a greater extent in ALDH2*2 mice. Our study comprehensively evaluated ALDH2s role in SCI by both genetically impairing and pharmacologically enhancing its activity, highlighting ALDH2 as a critical modulator of acrolein-mediated damage and suggesting its potential as a therapeutic target, especially for individuals with the ALDH2*2 mutation.

neuroscience↗

bioRxiv2025

Aperiodic neural dynamics define a novel signature of glioma-induced excitation-inhibition dysregulation

Diffuse gliomas remodel neuronal circuits with prognostic and therapeutic significance for patients. Electrophysiologic measures of cortical excitability hold promise for monitoring disease progression and evaluating therapeutic responses. The power law exponent (aperiodic slope) reflects the balance between excitatory and inhibitory activity within neuronal networks, a critical aspect of normal brain function often disrupted in neurological conditions. Despite its potential, the significance of the aperiodic slope in glioma-infiltrated tissue and its underlying cellular processes has not been fully investigated. Here, we integrate multi-modal electrophysiological analysis with transcriptomic profiling to analyze the aperiodic slope in both normal and glioma-infiltrated cortex. We determine that glioma infiltration induces a flattening of the aperiodic slope, indicating a shift toward excitation dominance that varies according to tumor subtype and correlates with impairments in semantic naming. Single-nucleus RNA sequencing revealed that cortical regions with flat aperiodic slope exhibit transcriptional programs enriched in glutamatergic signaling, membrane depolarization, and excitatory synaptic transmission. The aperiodic slope responds to pharmacologically induced changes in cortical inhibition during propofol administration, a GABAA agonist. Our results establish the aperiodic slope as a robust biomarker of glioma-associated excitation-inhibition imbalance, with potential applications in tumor classification and treatment monitoring.

cancer biology↗