Abstract

Direct electrical motor cortex stimulation with short-train High-Frequency Stimulation (HFS) for Motor Evoked Potentials (MEPs) has been used during supratentorial surgeries, but the safety threshold is poorly defined. This study aimed to establish a rat model for the investigation of neural damage in the cerebral cortex caused by high current HFS to aid in defining safety thresholds. We performed bilateral craniotomy on 12 rats. Cerebral sensory-motor cortex in one hemisphere was stimulated with a highfrequency current for 100 times. The rats were sacrificed, and the brains were sliced for Nissl, DAPI, and IBA-1 staining. Neural damage of the cerebral cortex was found in all cases, including markedly shrunken and pyknotic cells. IBA-1 staining revealed reactive microglia morphology in the lesion. DAPI staining showed nucleus degeneration and deformation. The cell density was significantly lower within the lesion compared to the contralateral unstimulated hemisphere. This study has established a brain lesion model caused by HFS on rats. These results suggest HFS may carry a risk of serious neural damage if repeatedly applied to the same brain site. More experiments are needed to fully understand the safety threshold of direct cortical stimulation with HFS for clinical use.

Keywords: Brain injuries; Direct cortical stimulation; High-frequency stimulation; Motor evoked potentials

Abbreviations: D: Duration of Each Pulse; HFS: High-frequency Stimulation; I: Current Intensity; IONM: Intraoperative Neurophysiological Monitoring; LFS: Low-frequency Stimulation; MEP: Motor Evoked Potentials; PFA: Paraformaldehyde; PBS: Phosphate-buffered Saline; Q: Charge Per Pulse; Qt: Total Charge; QDt: Total Charge Density