Potential pharmacological target of tight junctions to improve the BBB permeability in neonatal Hypoxic-Ischemic encephalopathy Diseases
Biochemical Pharmacology(2023)
摘要
Neonatal encephalopathy (NE) is a pathological condition that describes a neurocognitive malfunction in the newborn that arises from fetal, peripartum, or intrapartum events of multifactorial nature, having a poor prognosis and accounting for an incidence of 5-8 per 1000 live births. Neonatal hypoxic-ischemic encepha-lopathy (HIE) is one of the most studied paradigms of NE, caused by a scarce cerebral perfusion and oxygen supply during perinatal life. The cerebral hypoxic-ischemic insult promotes a loss of permeability of the blood-brain barrier (BBB), an essential structural intermediary of blood-brain communication. This permeability disruption is associated with an increase in inflammatory cytokines, an increase of adhesion molecules, and oxidative stress which disturb the tight junction (TJ) performance and enable transcytosis and paracellular leakage, ultimately leading to death from brain cells. In this context, TJs proteins are essential to preserving the barrier mechanical stability and signaling that modulates the brain-blood vessel multicellular domains, known as neurovascular units (NVU). Recent studies have proposed different strategies with neuroprotective effects that allow for maintaining or restoring the integrity and permeability of the BBB. This review identifies and discusses regulator mechanisms and novel aspects of TJs in the BBB disruption induced by cerebral hypoxic insults during the perinatal period, evaluating potential pharmacological strategies to safeguard BBB integrity.
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关键词
Neonatal Hypoxic-Ischemic Encephalopathy,Blood-Brain Barrier,Tight Junction,Neurovascular Unit,Hypoxia,Neonatal Diseases,Pharmacologic Therapy
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