Brain angiogenesis in developmental and pathological processes: neurovascular injury and angiogenic recovery after stroke

Pathophysiologic responses in brain after stroke are highly complex. Thus far, a singular focus on saving neurons alone has not revealed any clinically effective neuroprotectants. To address this limitation, the concept of a neurovascular unit was developed. Within this conceptual framework, brain function and dysfunction are manifested at the level of cell–cell signaling between neuronal, glial and vascular elements. For stroke, coordinated responses at the neurovascular interface will mediate acute as well as chronic events in ischemic and hemorrhagic brain tissue. In this minireview, we briefly survey two representative examples of neurovascular responses in stroke. During the early acute phase of neurovascular injury, blood–brain barrier perturbations should predominate with key roles for various matrix proteases. During the delayed phase, brain angiogenesis may provide the critical neurovascular substrates for neuronal remodeling. In this minireview, we propose the hypothesis that the biphasic nature of neurovascular responses represents an endogenous attempt by damaged parenchyma to trigger brain angiogenesis and repair. This phenomenon may allow acute deleterious signals to transition into beneficial effects during stroke recovery. Understanding how neurovascular signals and substrates make the transition from initial injury to angiogenic recovery will be important if we are to find new therapeutic approaches for stroke.