The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation

Preeclampsia (PE) is a complex hypertensive disorder of pregnancy characterized by new-onset maternal hypertension and multi-organ dysfunction. Although placental maladaptation and immune activation are well-established features of PE, growing evidence indicates that dysregulated neuro-immune-vascular integration critically contributes to disease initiation, progression, and long-term sequelae. Normal pregnancy requires coordinated immune and neural adaptations, particularly at the maternal-fetal interface, to support successful placentation. While placental pathology, angiogenic imbalance, and immune activation establish the systemic environment of PE, some neurological phenotypes (such as eclampsia and acute cerebral autoregulatory failure) are difficult to explain without involvement of central autonomic and sensory integration circuits that mediate the translation of peripheral inflammatory and vasoactive signals into neurovascular responses. Dysfunction of cerebral autoregulation has been proposed as a key mechanism underlying acute neurological complications, independent of classic placental factors. In PE, this finely tuned communication becomes spatially and functionally disrupted, triggering cascades of inflammatory and vascular pathology. Emerging studies suggest that neural signals, including autonomic activity and neuropeptide signaling, may modulate local immune phenotypes and vascular responses, thereby sustaining feed-forward cycles of inflammation and endothelial dysfunction. Altered neural inputs to peripheral immune organs may further bias myelopoiesis and amplify systemic inflammatory burden. At the central nervous system level, persistent neuroinflammation and blood-brain barrier disruption may potentiate systemic inflammatory signals, contributing to acute neurological manifestations and increased long-term cerebrovascular risk in women with prior PE. This review synthesizes evidence from human studies and experimental models to delineate neuroimmune mechanisms implicated in PE, identifies critical gaps in current knowledge, and highlights emerging concepts such as neuroimmune memory and neuro-metabolic crosstalk. We further discuss translational opportunities, including biomarker discovery, neuro-modulatory interventions, and advanced approaches such as single-cell and spatial omics. By integrating classical immunovascular paradigms with emerging neuroimmune insights, we propose a more comprehensive framework for understanding PE pathogenesis and for developing novel diagnostic and therapeutic strategies.