Neurovascular coupling dysfunction in encephalopathy: pathophysiological advances and clinical implications.

Neurovascular coupling (NVC) is a sophisticated and vital physiological mechanism that ensures the brain's intricate balance and optimal performance. It refers to the precise coordination between the brain's neural activity and the local cerebral blood flow (CBF), which is essential for meeting the metabolic demands of active neurons. This coupling allows for the efficient delivery of oxygen and nutrients to brain regions experiencing increased activity and facilitates the removal of metabolic waste products. In encephalopathy, a collective term for a wide range of conditions that impair brain function, NVC dysfunction has been identified as a key factor contributing to the progression of these disorders and the emergence of clinical symptoms. This comprehensive review aims to explore the complex pathophysiological mechanisms that lead to NVC dysfunction in several encephalopathic conditions. These include but are not limited to Alzheimer's disease (AD), Parkinson's disease (PD), cerebral small vessel disease (CSVD), stroke, migraine, traumatic brain injury (TBI) and epilepsy. Across the spectrum of encephalopathies discussed in this review, a unifying molecular target emerges: endothelin-1 (ET-1) and its receptors. ET-1, a potent vasoconstrictor produced by endothelial cells and astrocytes, is intricately linked to NVC dysfunction in these conditions. A thorough understanding of the role of NVC in encephalopathic disorders can inform the development of diagnostic tools and therapeutic strategies. For instance, identifying early markers of NVC dysfunction could facilitate early intervention and potentially slow disease progression. Moreover, targeting the restoration of NVC could become a novel therapeutic approach to mitigate symptoms and improve patient outcomes. This review also proposes new directions for future research, encouraging the exploration of NVC's complex interactions and its potential as a therapeutic target in the management of encephalopathic conditions.