Need for a Paradigm Shift in the Treatment of Ischemic Stroke: The Blood-Brain Barrier

Figure 1. Components of the neurovascular and the gliovascular units of the BBB.

Figure 2. (a) Components of the BBB and the neurovascular unit. The endothelium glycocalyx protects the vascular endothelium and prevents the adhesion of blood cells. The endothelium is impermeable through the paracellular spaces by means of a complex system of proteins that form the tight junctions (TJ). The adherent junctions facilitate the flexibility of the capillary to changes in the diameter of the vascular lumen. Through the endothelium, the passage of molecules necessary for the functioning of the CNS is allowed by various mechanisms, some passive and others linked to exchange or receptor pumps. Pericytes embedded in the basement membrane, astrocytic endfeet, and microglia complete the BBB. (b) BBB dysfunction in situations of chronic and subclinical cerebral ischemia. The increase in permeability is due primarily to the breakdown of the endothelium glycocalyx (1), which facilitates the adhesion and penetration of leukocytes through the endothelium (2), and the alteration of the selective transcellular permeability system, which allows the entry of water and proteins into the perivascular space (3). (c) Hours after the onset of acute cerebral ischemia, tight and adherens junctions…

Figure 3. Leukoaraiosis in a 67-year-old hypertensive patient with occasional headaches. (a) CT showing diffuse hypodensity (rarefaction) of the periventricular white matter. (b) T2-MRI of the same patient, with sharper hypersignals.

Figure 4. A 61-year-old woman with cardioembolic stroke in the territory of the middle cerebral artery. (a) In the first DWI-MRI (left) that corresponds to a cytotoxic oedema. (b) The same patient at 48 h (right). CT shows intense vasogenic oedema and hemorrhagic transformation of the infarct.

Figure 5. Correspondence of BBB alteration with neuroimaging in situations of chronic cerebral ischemia and the evolution of cytotoxic oedema to vasogenic oedema in acute cerebral ischemia.