Plasma NfL continued to increase during the acute and early subacute periods following AIS, predicted poorer 90-day functional outcomes, and trajectory modeling suggested taVNS was associated with a less pronounced rise in NfL and significantly lower NfL levels on Days 3 and 5 after last known normal compared with sham stimulation.
Plasma neurofilament light chain (NfL) levels continued to rise during the acute and early subacute periods following acute ischemic stroke.
Higher plasma NfL levels predicted poorer modified Rankin Scale (mRS) scores at day 90 following acute ischemic stroke.
Several factors were identified as significantly affecting NfL levels after acute ischemic stroke, including imaging-based measures of cerebral edema and infarct volume, race, IL-10 at admission, and thrombolytic treatment.
After regressing NfL on identified confounding factors, treatment assignment (taVNS vs. sham) was not significantly associated with overall NfL levels.
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 last known normal compared with sham stimulation.
The study design was a prospective, randomized, open-label, blinded-endpoint, sham-controlled trial with 35 acute ischemic stroke patients.
This research suggests that a protein called neurofilament light chain (NfL), which is released into the blood when brain nerve cells are damaged, keeps rising for several days after an ischemic stroke rather than stabilizing quickly. In a small clinical trial of 35 stroke patients, higher NfL levels in the days following stroke were linked to worse functional outcomes three months later, supporting the idea that NfL could serve as a useful blood test to predict how well stroke patients will recover. The study also identified several factors that influence NfL levels, including the size of the stroke, brain swelling seen on imaging, the patient's race, a specific immune marker (IL-10) measured at hospital admission, and whether the patient received clot-dissolving medication. The trial also tested whether a non-invasive nerve stimulation technique called transauricular vagus nerve stimulation (taVNS)—which involves gentle electrical stimulation applied to the ear—could reduce the brain damage occurring after stroke. When analyzing the trajectory of NfL over time, patients who received taVNS showed a smaller rise in NfL and had significantly lower NfL levels on Days 3 and 5 after their stroke compared to patients who received a sham (inactive) treatment. However, when looking at overall NfL levels while accounting for other influential factors, the difference between the two groups did not reach statistical significance, likely due to the small sample size. This research suggests that NfL is a promising blood biomarker for monitoring ongoing brain injury and predicting recovery after ischemic stroke, and that taVNS may help reduce the extent of brain cell damage that continues after a stroke. The authors note that larger and longer trials are needed to determine whether taVNS can meaningfully protect the brain after stroke and whether NfL can reliably guide clinical decision-making in stroke care.
Tan G, Laurido-Soto O, Huguenard A, Dhar R, Lee J, Leuthardt E. (2026). Neurofilament light chain dynamics following ischemic stroke and their modulation by transauricular vagus nerve stimulation.. Scientific reports. https://doi.org/10.1038/s41598-026-57557-4