Abstract
Ischemic stroke is a leading cause of death and disability worldwide. Although advances in interventions for acute ischemic stroke (AIS) restore blood flow to ischemic tissue, neuronal injury continues to evolve following recanalization. There is a critical need to develop interventions that can attenuate this progressive injury. This study investigated plasma neurofilament light chain (NfL) as a marker of neuroaxonal damage after AIS. In a prospective, randomized, open-label, blinded-endpoint, sham-controlled trial, 35 AIS patients received twice-daily taVNS or sham stimulation for five days or until discharge. We measured NfL at four time points after last known normal (LKN): Days 0 (within 24 h), 1, 3, and 5. We evaluated whether transauricular vagus nerve stimulation (taVNS) modulates its dynamics after AIS. Plasma NfL level continued to increase during the acute and early subacute periods following AIS. Higher NfL levels predicted poorer modified Rankin Scale scores at day 90. We identified factors that affect NfL levels, including imaging-based measures of cerebral edema and infarct volume, race, IL-10 at admission, and thrombolytic treatment. After regressing NfL on the identified factors, treatment assignment was not significantly associated with overall NfL levels. Nevertheless, NfL-trajectory modeling suggested that taVNS was associated with a less pronounced rise in NfL after AIS and with significantly lower NfL levels on Days 3 and 5 after LKN, compared with sham stimulation. Our findings inform the clinical use of NfL as a biomarker of long-term functional recovery after AIS and warrant evaluation in larger and longer trials to determine whether taVNS can meaningfully mitigate neuroaxonal injury after AIS.Trial registration: NCT05390580, https://clinicaltrials.gov/study/NCT05390580-Study started/registered: 26/09/2022.