Ultrastructural pathology of endothelial tight junctions in human brain oedema

Abstract

Cortical biopsies of patients with the diagnosis of complicated brain trauma, congenital hydrocephalus, brain vascular anomaly, and brain tumour are studied with the electron microscope using cortical biopsies of different cortical brain regions to analyze the alterations of endothelial junctions, and their participation in the pathogenesis of human brain oedema. In moderate oedema, most endothelial tight junctions are structurally closed and intact, while in some cases of severe oedema, the opening of tight endothelial junctions is observed. In very severe brain oedema, a considerable enlargement of interjunctional pockets of extracellular space is also seen suggesting that in highly increased cerebrovascular permeability, the endothelial junctions are open in their entire extent, and that an intercellular or paracellular route through interendothelial clefts for transferring haematogenous oedema fluid from blood to the capillary basement membrane and the brain parenchyma is formed, contributing to the formation of brain oedema. High intensity brain trauma, seizures, osmotic forces, hypoxic conditions, and alteration of tight junctions proteins would explain the opening of endothelial junctions in severe and complicated brain oedema. In congenital hydrocephalus, the capillary wall shows evident signs of blood-brain barrier dysfunction characterized by closed and open interendothelial junctions, increased endothelial vesicular and vacuolar transport, thin and fragmented basement membrane with areas of focal thickening, and discontinuous perivascular astrocytic end-feet. The perivascular space is notably dilated and widely communicated with the enlarged extracellular space in the neuropil, showing the contribution of damaged endothelial junction to the formation of interstitial or hydrocephalic brain oedema. Altered expression of tight junction proteins could cause a blood-brain barrier breakdown following brain injury and hypoxic conditions leading to brain oedema. The results are compared with those found in experimental brain oedema. Some controversial results are also described.