Protein markers of hypoxic-ischemic lesions of the CNS in the perinatal period

Abstract

Pre-eclampsia, eclampsia, and acute intranatal hypoxia often lead to the development of perinatal hypoxic-ischemic lesions of the CNS. The disease-related structural changes are periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH). Hypoxic-ischemic lesions of the CNS in the perinatal period can result in hydrocephalus, microcephaly, infantile cerebral paralysis (ICP), epilepsy, and psychomotor retardation. It is not always possible to accurately evaluate the disease severity and make a prognosis using routine methods of clinical, instrumental, and laboratory examination. It has been proven that a perinatal hypoxic-ischemic lesion of the CNS is always accompanied by the alteration of blood-brain barrier (BBB) permeability; therefore, the neuron-specific proteins (NSPs) outside the brain may be considered as markers of a pathologic process. To date more than 120 NSPs, in particular the non-enzymatic Ca2+-binding NSP, non-enzymatic NSPs responsible for cell recognition and cell adhesion, contractile and cytoskeletal proteins in nerve tissue, regulatory and transport secreted NSPs, myelin proteins, and glial NSPs have more or less detailed descriptions. To evaluate the state of the blood-brain barrier, it is rational to use the most-studied proteins, which are markers for neurons and astrocytes. These are the glial fibrillary acidic protein (GFAP) and the neuron-specific enolase (NSE). They do not cross the BBB and practically cannot be determined in serum under normal conditions. When BBB permeability is compromised, NSPs penetrate into the peripheral blood and may be measured. Dynamic determination of NSPs in serum may be used to evaluate BBB resistance, to estimate the severity of a CNS lesion, and to determine the prognosis for children with a perinatal hypoxic-ischemic lesion of the CNS.