Endothelin peptides in brain diseases

Recently, scientists interested in diseases of the human brain have paid much attention to the endothelin group of peptides. Under normal conditions they are found in some types of neurons and in endothelial cells of microvessels but not in glial cells. This review focuses on the endothelin peptides and their involvement in various brain diseases. Particular attention is paid to their expression in reactive astrocytes seen in many pathological conditions of the human brain. Endothelin-1 is a very potent vasoconstrictor which may be involved in the vasospasm occurring in subarachnoid haemorrhage. Intracerebral injection or application to cerebral arteries in animals will cause a focal necrosis, apparently due to severe vasoconstriction. Reactive astrocytes occurring in cases with infarcts, lacunae, Alzheimer's disease, progressive multifocal leukoencephalopathy (PML) and subacute sclerosing panencephalitis (SSPE) express endothelin-like immunoreactivity. Astrocytes in vitro may produce, store and release endothelins. To some extent astrocytes grown in vitro mimic reactive astrocytes in vivo since in cultures astrocytes are removed from their natural environment which may trigger reactive responses. Therefore, in vivo reactive astrocytes may produce, store and release endothelins just as in vitro. If endothelins are released from reactive astrocytes they may act as mitogens and may influence microcirculation by inducing vasoconstriction of intracerebral arterioles. In such ways endothelins may contribute to the final lesions seen in cases with infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain.