Neurovascular protection pathways

Neurovascular protection pathways refer to a complex network of signaling mechanisms and cellular interactions aimed at maintaining the integrity and function of the neurovascular unit (NVU) [3, 5]. The NVU is a functional entity comprising neurons, glial cells (astrocytes, microglia, oligodendrocytes), and vascular cells (endothelial cells, pericytes, smooth muscle cells) [3, 13]. These pathways are critical for regulating the blood-brain barrier (BBB), cerebral blood flow, and the chemical microenvironment of the brain [5, 11]. In diseases such as ischemic stroke, Alzheimer's disease, and traumatic brain injury, these pathways are disrupted, leading to neuroinflammation, oxidative stress, and neuronal death [1, 6, 9]. Therapeutic strategies targeting these pathways aim to provide "neurovascular protection" by simultaneously addressing multiple components of the NVU, rather than focusing solely on neurons [5, 13]. This includes activating endogenous antioxidant defenses like the Nrf2-Keap1 pathway, modulating inflammatory responses via PPARα, and promoting vascular and neural repair through factors like VEGF and Wnt signaling [1, 2, 10, 12]. Despite promising preclinical results, many drugs targeting these pathways have faced challenges in clinical translation due to the complexity of the human brain and the narrow therapeutic windows in acute conditions [4, 11].

Other names

Neurovascular unit protectionNVU protection pathwaysNeurovascular signaling pathwaysVasculo-neuronal-inflammatory triad

Activation of endogenous antioxidant defenses (e.g., Nrf2-Keap1), modulation of neuroinflammation (e.g., PPARα activation), stabilization of the blood-brain barrier (e.g., VE-cadherin maintenance), and promotion of neurovascular repair and regeneration (e.g., VEGF and Wnt signaling).