Eppur si muove: the dynamic brain pericyte

Brain pericytes, the mural cells of cerebral microvessels, were long regarded as controversial, mainly due to their morphological and functional heterogeneity, plasticity, and variable expression of alpha-smooth muscle actin (α-SMA). However, they have recently emerged as a focal point in neuroscience research owing to their critical roles in regulating the blood-brain barrier (BBB), neuroinflammation, cerebral blood flow (CBF), and angiogenesis. In particular, the regulation of CBF and angiogenesis involves highly dynamic processes such as contraction and migration. By converting chemical energy into mechanical work, motor proteins, like myosin-through their interactions with intracellular filaments, primarily actin-play a crucial role in these processes.

In this review, we describe the contractile elements of pericytes, highlighting the relevance of α-SMA and myosin II isoforms containing the Myh11 and Myh9 heavy chains. In addition, we discuss recent advances in understanding how distinct pericyte subtypes contribute to mechanical force generation during the regulation of vessel diameter, pericyte migration, and the dynamic remodelling of their cellular processes. Furthermore, we highlight how ensheathing pericytes, which envelop the initial branches of the capillary bed and express high levels of α-SMA, initiate robust vasorelaxation during neurovascular coupling. In contrast, α-SMA-low capillary pericytes regulate basal vascular tone but also actively sense and respond to local glucose levels and neuronal activity. While ensheathing pericytes play a central role in sustained vasoconstriction following ischaemia, capillary pericytes are primarily responsible for secondary vasoconstrictive events during stroke.

Taken together, pericytes are dynamic cells capable of exerting diverse forms of mechanical force, playing essential roles in both physiological and pathological conditions. Eppur si muove-and yet it moves.