Date of Presentation

5-2-2024 12:00 AM

College

Rowan-Virtua School of Osteopathic Medicine

Poster Abstract

Background: The blood-brain barrier (BBB), formed by the vascular endothelium, astrocytic foot processes, pericytes, is a highly selective barrier that is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI).1 Loss of BBB integrity leads to the proliferation of pro-inflammatory cytokines, including TNFɑ, IL-1β, and IL-6.2 Moderate inflammation has a beneficial response in the system following an acute injury. However, prolonged inflammation has been known to perturb homeostasis and have devastating neurodegenerative effects.4-7 Therefore, anti-inflammatory compounds are extensively tested for their potential therapeutic role in lowering these inflammatory changes. Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs).8 Hence, lipoxins are recognized as “breaking signals” in the inflammatory process. One form of lipoxin, Lipoxin A4 (LXA4), has been found to decreased production of proinflammatory mediators, inhibit neutrophils chemotaxis and infiltration to the site of injury, and promote the phagocytic clearance of debris by macrophages.4,12,13,14 This literature review aims at understanding the neuroprotective role of LXA4 in reducing BBB breakdown and reinstating BBB integrity.

Hypothesis: LXA4 treatment attenuates acute inflammation and reinstates the BBB integrity in acute BBB breakdown and inflammation.

Methods: A comprehensive literature search was performed using PubMed and EMBASE databases.

Conclusion: LXA4 serves a critical role in resolution of inflammatory process by regulating the activation of monocytes and modulating the generation of reactive oxygen species (ROS). LXA4 treatment has shown to reinstate the BBB integrity in acute BBB breakdown models.

Keywords

Blood-Brain Barrier, Neurodegenerative Diseases, Alzheimer Disease, Traumatic Brain Injury, Lipoxins, Cytokines, Inflammation Mediators, Inflammation

Disciplines

Medical Neurobiology | Medicine and Health Sciences | Nervous System | Nervous System Diseases | Neuroscience and Neurobiology

Document Type

Poster

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May 2nd, 12:00 AM

The Neuroprotective Role of Lipoxin A4 in Reinstating Blood Brain Barrier Integrity in Neuroinflammatory Disease Processes

Background: The blood-brain barrier (BBB), formed by the vascular endothelium, astrocytic foot processes, pericytes, is a highly selective barrier that is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI).1 Loss of BBB integrity leads to the proliferation of pro-inflammatory cytokines, including TNFɑ, IL-1β, and IL-6.2 Moderate inflammation has a beneficial response in the system following an acute injury. However, prolonged inflammation has been known to perturb homeostasis and have devastating neurodegenerative effects.4-7 Therefore, anti-inflammatory compounds are extensively tested for their potential therapeutic role in lowering these inflammatory changes. Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs).8 Hence, lipoxins are recognized as “breaking signals” in the inflammatory process. One form of lipoxin, Lipoxin A4 (LXA4), has been found to decreased production of proinflammatory mediators, inhibit neutrophils chemotaxis and infiltration to the site of injury, and promote the phagocytic clearance of debris by macrophages.4,12,13,14 This literature review aims at understanding the neuroprotective role of LXA4 in reducing BBB breakdown and reinstating BBB integrity.

Hypothesis: LXA4 treatment attenuates acute inflammation and reinstates the BBB integrity in acute BBB breakdown and inflammation.

Methods: A comprehensive literature search was performed using PubMed and EMBASE databases.

Conclusion: LXA4 serves a critical role in resolution of inflammatory process by regulating the activation of monocytes and modulating the generation of reactive oxygen species (ROS). LXA4 treatment has shown to reinstate the BBB integrity in acute BBB breakdown models.

 

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