Frequency-dependent modulation of cerebral blood flow and cardiorespiratory function by trigeminal ophthalmic branch (V1) stimulation in rats

The ophthalmic branch of the trigeminal nerve (V1) represents a promising target for noninvasive neuromodulation in the context of neurological research. Nevertheless, its physiological effects on cerebral and systemic circulation remain inadequately understood. This study aimed to investigate the effect of electrical stimulation of V1 on regional cerebral blood flow (rCBF), heart rate (HR), blood pressure (BP; measured as mean arterial pressure, MAP), and respiratory rate (RR) in rats at two frequencies (20 and 100 Hz). Stimulation at 20 Hz increased rCBF, HR, and MAP, whereas stimulation at 100 Hz produced minimal effects. These findings suggest the occurrence of frequency-dependent activation of autonomic pathways, potentially mediated by brainstem regions such as the rostral ventrolateral medulla. RR responses varied among animals, exhibiting either increased or decreased RR during stimulation. Mixed-effects analysis revealed that RR changes were not only influenced by the effects of direct stimulation but also by complex interactions with HR and MAP fluctuations, suggesting coordination between the respiratory and cardiovascular control systems. In some animals, a delayed reduction in the RR after stimulation may indicate parasympathetic involvement or inhibitory network activity. Given the anatomical accessibility of V1, the observed rCBF increase may provide a physiological basis for future studies on cerebrovascular regulation. These findings provide foundational evidence that V1 stimulation modulates cerebrovascular and autonomic function in a frequency- and individual-dependent manner, offering a physiological basis for future translational research.