Evaluation of Tight Junction Integrity in Brain Endothelial Cells Using Confocal Microscopy.

The blood-brain barrier (BBB) is a highly complex and dynamic microvascular barrier that protects the brain parenchyma from the entry of pathogens, toxins, and other macromolecules and is a critical structure that helps to maintain brain homeostasis. The BBB is formed mainly by brain capillary endothelial cells and perivascular astrocytes and pericytes. One of the primary properties of the BBB is a tight regulation of paracellular permeability due to the presence of tight junctional complexes (also, adherens and gap junctions) between the neighboring microvascular endothelial cells.

Determination of Tight Junction Integrity in Brain Endothelial Cells Based on Tight Junction Protein Expression.

Blood-brain barrier (BBB) dysfunction and hyperpermeability that occurs following traumatic and ischemic insults lead to various downstream ill effects such as cerebral edema and elevation of intracranial pressure. The inter-endothelial tight junctions that consist of tight junction proteins are critical regulators of BBB dysfunctions and hyperpermeability. The major tight junction-associated proteins of the BBB are occludin, claudins, and junctional adhesion molecules that are intracellularly linked to the adaptor protein zonula occludens-1 (ZO-1).

Exploring blood-brain barrier hyperpermeability and potential biomarkers in traumatic brain injury.

Blood-brain barrier breakdown and associated vascular hyperpermeability leads to vasogenic edema in traumatic brain injury (TBI). Tight junctions maintain blood-brain barrier integrity; their disruption in TBI holds significant promise for diagnosis and treatment. A controlled cortical impactor was used for TBI in mouse studies.

A Mouse Controlled Cortical Impact Model of Traumatic Brain Injury for Studying Blood-Brain Barrier Dysfunctions.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. It is a silently growing epidemic with multifaceted pathogenesis, and current standards of treatments aim to target only the symptoms of the primary injury, while there is a tremendous need to explore interventions that can halt the progression of the secondary injuries. The use of a reliable animal model to study and understand the various aspects the pathobiology of TBI is extremely important in therapeutic drug development against TBI-associated complications.

Attenuation of Blood-Brain Barrier Breakdown and Hyperpermeability by Calpain Inhibition.

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema are hallmark features of several brain pathologies, including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1β (IL-1β) that is up-regulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability, but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain.

Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition.

Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema.

Doxycycline Attenuates Lipopolysaccharide-Induced Microvascular Endothelial Cell Derangements.

Introduction: Lipopolysaccharide (LPS) is known to induce vascular derangements. The pathophysiology involved therein is unknown, but matrix metalloproteinases (MMPs) may be an important mediator. We hypothesized that in vitro LPS provokes vascular permeability, damages endothelial structural proteins, and increases MMP activity; that in vivo LPS increases permeability and fluid requirements; and that the MMP inhibitor doxycycline mitigates such changes.

Tissue inhibitor of metalloproteinase-2 inhibits burn-induced derangements and hyperpermeability in microvascular endothelial cells.

Background: Burns induce microvascular hyperpermeability. We hypothesize that this occurs partly through an imbalance between matrix metalloproteinases (MMPs) and endogenous MMP inhibitors such as tissue inhibitors of metalloproteinases (TIMPs), and that such derangements can be attenuated with the use of TIMP-2.

Method: Rats underwent either sham or burn: serum and tissue were collected.

Oxygen-glucose deprivation and reoxygenation as an in vitro ischemia-reperfusion injury model for studying blood-brain barrier dysfunction.

Ischemia-Reperfusion (IR) injury is known to contribute significantly to the morbidity and mortality associated with ischemic strokes. Ischemic cerebrovascular accidents account for 80% of all strokes. A common cause of IR injury is the rapid inflow of fluids following an acute/chronic occlusion of blood, nutrients, oxygen to the tissue triggering the formation of free radicals.

Blood-brain barrier dysfunction following traumatic brain injury.

Traumatic brain injury is a serious cause of morbidity and mortality worldwide. After traumatic brain injury, the blood-brain barrier, the protective barrier between the brain and the intravascular compartment, becomes dysfunctional, leading to leakage of proteins, fluid, and transmigration of immune cells. As this leakage has profound clinical implications, including edema formation, elevated intracranial pressure and decreased perfusion pressure, much interest has been paid to better understanding the mechanisms responsible for these events.

Tumor necrosis factor-α disruption of brain endothelial cell barrier is mediated through matrix metalloproteinase-9.

Traumatic brain injuries cause vascular hyperpermeability. Tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and caspase-3 may be important in these processes but the relationship between them has not been investigated. We hypothesized that TNF-α regulates caspase-3-mediated hyperpermeability and blood brain barrier damage and hyperpermeability directly or indirectly via activation of MMP-9.

Melatonin inhibits thermal injury-induced hyperpermeability in microvascular endothelial cells.

Background: Burns induce systemic inflammatory reactions and vascular hyperpermeability. Breakdown of endothelial cell adherens junctions is integral in this process, and reactive oxygen species (ROS) and proteolytic enzymes such as matrix metalloproteinase-9 (MMP-9) play pivotal roles therein. Outside trauma, melatonin has shown to exhibit anti-MMP activity and to be a powerful antioxidant.