Timothy G. White, MD: No financial relationships to disclose
Introduction: Cortical spreading depolarizations (CSD) drive secondary neurological injury in many pathologies, including ischemic stroke where they result in spreading ischemia and the demise of the ischemic penumbra. Recent studies have focused on the use of various drugs to prevent CSDs; however, their results are mixed. New treatment strategies are needed. Trigeminal nerve stimulation (TNS) is a noninvasive bioelectronic modality shown to improve experimental outcomes in subarachnoid hemorrhage and traumatic brain injury by regulating cerebral perfusion. We sought to investigate the ability of TNS to decrease CSD generation in an ischemic stroke model
Methods: 32 male Sprague-Dawley rats were randomized to four study groups: (1) control animals with permanent middle cerebral artery occlusion (MCAO); (2) MCAO animals with Pre-TNS (intermittent TNS for 60 min); (3) MCAO rats with Post-TNS (low dose); and (4) MCAO rats with Post-TNS (high dose). The TNS was achieved percutaneously via the infraorbital nerve. Epidural electrodes were implanted to record CSDs. Lesion volume was assessed.
Results: Upon occlusion, CBF immediately fell by 68±11%. Spontaneous waves of depolarization appeared in the ischemic penumbra zone, averaging about eight events (8.1±2.1; n=8) over the 3 h after occlusion. The first CSD appeared at 7.1±3.6 min after occlusion. Pre-TNS treatment significantly lengthened the latency until the appearance of the first CSD almost 7-fold, and decreased their number by 53% (3.8±0.8 vs. 8.2±2.1; n=8). Pre-TNS treatment just before MCAO also significantly reduced infarction volumes by 34% (from 218.5±42.6 mm3 to 143.1±24.7 mm3; n=8). Both low and high dose of Post-TNS treatment also significantly reduced infarction volumes by 39% and 51%, respectively.
Conclusion : TNS can selectively reduce the deleterious consequences of CSDs in ischemic brain tissue resulting in a dose dependent decrease in lesion volume. The results suggest that TNS can salvage at-risk penumbra after ischemic stroke.
