Targeting the neurovascular unit in brain trauma

Abstract

Although the neurovascular unit was originally developed as a conceptual framework for stroke, it is now recognized that these cell-cell interactions play critical roles in many other CNS disorders as well. In brain trauma, perturbations within the neurovascular unit may be especially important. Changes in neurovascular coupling may disrupt blood flow and metabolic regulation. Disruption of transmitter release-reuptake kinetics in neurons and astrocytes may augment excitotoxicity. Alterations in gliovascular signaling may underlie blood-brain barrier disruptions and traumatic edema. Perturbations in cell-cell signaling between all neuronal, glial, and vascular compartments may increase susceptibility to cell death. Finally, repairing the brain after trauma requires the integrated restoration of all neural, glial, and vascular connectivity for effective functional recovery. Just as in stroke, saving neurons alone may also be insufficient for treating brain trauma. In this minireview, we attempt to briefly highlight some of these pathways to underscore the importance of rescuing the entire neurovascular unit in brain trauma.

Keywords: Endothelial; Glia; Neuron; Neuroprotection; Traumatic brain injury.

Figure 1

Cross talk between multiple cell types in CNS and non‐CNS compartments after TBI. After TBI, perturbations in cell–cell signaling between all neuronal, glial, and vascular compartments may increase susceptibility to cell death. Changes in neurovascular coupling may disrupt blood flow and metabolic regulation. Disruption of transmitter release‐reuptake kinetics in neurons and astrocytes may augment excitotoxicity. Alterations in gliovascular signaling may underlie blood–brain barrier disruptions and traumatic edema. Finally, repairing the brain after trauma requires the integrated restoration of all neural, glial, and vascular connectivity for effective functional recovery.