Plasminogen Activator Inhibitor – 1’s Effects on Blood-Brain Barrier Permeability Open Access

Abstract

The blood-brain barrier (BBB) is a semipermeable membrane between the body’s circulating blood and central nervous system (CNS) consisting of astrocytes and endothelial cells as well as pericytes on a basement membrane that maintains homeostasis by regulating what molecules can enter the brain. Stroke damages the brain by cutting off its blood supply, usually through a thrombus reaching the brain, and this causes a series of pathological increases to the permeability of the BBB. The clot is broken down by plasmin, which is facilitated by its cleaving from plasminogen by tissue-type plasminogen activator (tPA). Plasminogen activator inhibitor – 1 (PAI-1) inhibits this process, slowing thrombolysis. Previous work has established that tPA is able to mitigate the negative changes seen in the BBB, but no studies have been done on PAI-1’s effect on the BBB. It was found that treatment with PAI-1 induced a decrease in the permeability of an in vitro model of the BBB. However, PAI-1 knockout mice did not show any significant difference in expression of blood protein IgG in the brain, indicating no change in the permeability of the BBB.

Table of Contents

Table of Contents

 

Introduction – 1

Methods – 3

           Animals and Reagents – 3

           Cell Culture – 5

           In Vitro Model of the BBB – 6

           Immunohistochemistry of Mouse Brain Slices – 7

           Western Blot of Cerebral Cortex Lysate – 8

           Statistical Analyses – 9

Results – 9

In Vitro BBB Model Resistance Analysis – 9

Immunohistological Analysis – 10

           Western Blot Analysis – 11

Discussion – 12

Conclusions – 15

Conflicts of Interest – 15

References – 15

 

Figures

Figure 1 – 10

Figure 2 – 11

Figure 3 - 12

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Physiology Biology, Neuroscience Biology, General
Keyword	Plasminogen Activator Inhibitor - 1 Stroke Blood-Brain Barrier Plasminogen Activator
Committee Chair / Thesis Advisor	Smith, Yoland, Emory University
Committee Members	Reyes, Miguel, Emory University Faundez, Victor, Emory University

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