Progesterone in the Treatment of Transient Ischemic Stroke: A Dose-Response Study Open Access

Abstract

Abstract
Progesterone in the Treatment of Transient Ischemic Stroke: A Dose-Response Study
By Justiss A. Kallos

Stroke is the third leading cause of death in America and accounts for 6% of the total U. S. health care budget. In spite of the devastating effects stroke exerts on society, only one treatment has ever been developed that has passed clinical trials: tissue plasminogen activator (tPA). Unfortunately, tPA use is limited to less than 5% of stroke victims, leaving 95% without viable treatment. Studies conducted in numerous neural insult models have identified progesterone (PROG) as a potent, pleiotropic neuroprotective steroid. Preliminary studies conducted using PROG in the treatment of murine ischemic stroke models have demonstrated that PROG may also be neuroprotective in stroke. The aim of this study was to determine the best dose of PROG for the treatment of transient ischemic stroke in middle-aged rats. An intraluminal filament and suture method was used to induce a transient (2 h) occlusion in the right middle cerebral artery. Three doses of PROG were examined: 8 mg/kg, 16 mg/kg, and 32 mg/kg. Treatment was administered two and six hours post-ischemia, then once daily for seven consecutive days; the last two doses were tapered in order to prevent PROG withdrawal syndrome. Cognitive and behavioral outcomes were evaluated using accelerating rotarod and Morris water maze paradigms. Twenty-two days post-occlusion, rats were perfused and infarct volume quantified. Results, in conjunction with previously reported findings, suggest that 8 mg/kg of PROG is within the ideal therapeutic range for treating ischemic stroke. Further studies should confirm these findings in other models of stroke and in models of populations that are at a higher risk for developing stroke, such as diabetic and hypertensive populations.

Table of Contents

Table of Contents

Introduction……………………………………………………………..………………………..1

· Stroke……………………………………………………….…………...........………………1

· Progesterone and Traumatic Brain Injury.……………….…………………...4

· Progesterone………………………………………………………………………….........5

· Progesterone and Stroke……………………………………………………….……….6

Method………...…………………………………………………………………………………...7

· Subjects….…………………………………………………………………….……........….7

· Injury…………………………………………………………………………………............8

· Progesterone Treatment………………………………………………………………...9

· Behavioral Testing……………………………………………………………………......9

· Histological Analysis……………………………………………………………….......11

· Statistical Analysis………………………………………………………………….......12

Results……………………………………………………………………………………………..12

· Rotarod………………………………………………………………………………..........12

· Morris Water Maze………………………………………………………………….......13

· Histology............................................................................14

Discussion…………………………………………………………………………..……………14 References……………………………………………………………………………………….19 Tables and Figures…………………………………………………………………………..25

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Pharmacology Health Sciences, General Health Sciences, Medicine and Surgery
Keyword	Progesterone Dose-Response Stroke
Committee Chair / Thesis Advisor	Stein, Donald G, Emory University
Committee Members	Konner, Melvin J, Emory University Dyer, Brian, Emory University

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