Abstract
Disorders of the developing brain represent a major health problem. The neurological manifestations of brain lesions can range from severe clinical deficits to more subtle neurological signs or behavioral problems and learning disabilities, which often become evident many years after the initial damage. These long-term sequelae are due at least in part to central nervous system immaturity at the time of the insult. The blood-brain barrier (BBB) protects the brain and maintains homeostasis. BBB alterations are observed during both acute and chronic brain insults. After an insult, excitatory amino acid neurotransmitters are released, causing reactive oxygen species (ROS)-dependent changes in BBB permeability that allow immune cells to enter and stimulate an inflammatory response. The cytokines, chemokines and other molecules released as well as peripheral and local immune cells can activate an inflammatory cascade in the brain, leading to secondary neurodegeneration that can continue for months or even years and finally contribute to post-insult neuronal deficits. The role of the BBB in perinatal disorders is poorly understood. The inflammatory response, which can be either acute (e.g., perinatal stroke, traumatic brain injury) or chronic (e.g., perinatal infectious diseases) actively modulates the pathophysiological processes underlying brain injury. We present an overview of current knowledge about BBB dysfunction in the developing brain during acute and chronic insults, along with clinical and experimental data.
Highlights
The blood-brain barrier (BBB) is a physical barrier essential for the maintenance of a precisely regulated intracerebral microenvironment
The formation of tight junctions (TJs) takes place at the same time as angiogenesis (Virgintino et al, 2004), and even the first vessels to invade the avascular neuroectoderm are impermeable to albumin and immunoglobulins
Understanding the changes that occur in the BBB during normal development is critical, as it is a site of possible www.frontiersin.org
Summary
The blood-brain barrier (BBB) is a physical barrier essential for the maintenance of a precisely regulated intracerebral microenvironment. Influx and efflux transporters, metabolic enzymes, the extracellular matrix, astrocytic endfeet etc. All these structures together constitute the Neurovascular Unit (NVU), and are believed to be essential for the regulation of BBB permeability (Ballabh et al, 2004). Fetal brain vessels exhibit different, and in some respects increased, transport properties for amino acids and other metabolites, reflecting the higher demand for nutrients in the developing CNS (Ek et al, 2001, 2006; Johansson et al, 2006, 2008; Saunders et al, 2012). Understanding the changes that occur in the BBB during normal development is critical, as it is a site of possible www.frontiersin.org
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