Blood-brain barrier dysfunction in disorders of the developing brain

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.

Ischemic-Reperfusion Injury Increases Matrix Metalloproteinases and Tissue Metalloproteinase Inhibitors in Fetal Sheep Brain

“…We visualized the signals using enhanced chemiluminescence (ECL Prime; GE Healthcare Bio-Sciences, Pittsburgh, PA, USA) before exposure to autoradiographic film (Phenix, Candler, NC, USA). We detected pro-MMP-2, cleaved-MMP-2, MMP-8, MMP-13, TIMP-1, TIMP-2, TIMP-3, TIMP-4, β-actin, and vinculin bands at 72,64,53,54,26,24,26,25,42, and 117 kDa, respectively. Omission of the primary antibodies eliminated the chemiluminescent signals, thereby establishing the specificity of the primary antibodies to detect the specific protein bands.…”

“…Consequently, it is important to understand the effects of different durations of reperfusion after ischemia on brain injury to determine therapeutic strategies that could attenuate the untoward effects of perinatal brain damage [24]. Accumulating evidence suggests that there is an association between BBB dysfunction and changes in MMPs and TIMPs after hypoxic-ischemic brain injury in the neonatal rodent brain [13,25,26]. However, the expression profiles of MMPs and TIMPs have not previously been examined after ischemia in the brain of a large mammalian fetus.…”

Blood–brain barrier and laser technology for drug brain delivery

“…32 For instance, tight junctions appear on eight weeks of gestation in human, at 13 days in mice when the¯rst vessels appear in the cortex. 33 But, gene expression of tight junctions undergoes changes from postnatal period to adulthood.…”

Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders

“…Indeed, while the Blood Brain Barrier (BBB) as well the blood-CSF barrier are generally considered to have a highly selective permeability to blood compounds or drugs [159, 160], recent studies suggest that exosomes have the ability to cross the BBB in both directions, although the route of transfer remains unclear [161–164]. Moreover, exosomes were shown to be able to enter the brain parenchyma at the choroid plexus and were internalized both in neurons and glial cells (in-vitro and in-vivo rodent studies) [99].…”