Exacerbation of sensory dysfunction by hematoma-induced circuitry damage in a mouse model of thalamic hemorrhage.

Sensory impairment following stroke is a prevalent and challenging complication that imposes significant burdens and risks on patients. Despite the frequency of hemorrhage-induced sensory impairments in the thalamus, a comprehensive understanding of the underlying mechanisms and therapeutic targets remains incomplete. Here, we examine circuit connectivity and electrophysiological properties to study pathogenesis, as well as molecular target efficacy. Using a mouse model of thalamic hemorrhage and conducting behavioral assessments, thalamic hemorrhage can induce specific sensory dysfunction. Within the context of thalamic-related circuitry connections, damage thresholds in upstream circuits are higher compared to downstream regions. Electrophysiological characterization revealed that post-hemorrhagic thalamic neurons exhibited narrower action potential (AP) widths and reduced decay times, indicating heightened neuronal excitability. Additionally, transcriptomic analysis identified the PI3K-AKT signaling pathway and pharmacological inhibition targeting this pathway significantly mitigated the severity of sensory impairments. These findings provide novel insights into the pathogenesis of sensory impairments and present potential therapeutic targets for post-hemorrhagic sensory impairments.