Influence of Isoflurane on the Integrity of the Blood Brain Barrier
Abstract
The blood brain barrier (BBB) is a highly regulated structure that provides a stable microenvironment for proper neuronal functioning. An emerging body of evidence suggests that a single exposure to volatile anesthetics, like isoflurane, can reversibly alter BBB structure and function. Complex trauma patients often require multiple operations. The effects of repeated isoflurane exposures on BBB structure and function remain unidentified. Therefore, the purpose of this dissertation is to evaluate the effects of repeated exposures to isoflurane on the structure, function, and permeability of the BBB. Methods: Adult (8-10 Week) male Sprague Dawley Rats were divided into 4 groups: control, single prolonged exposure (1PE), single brief exposure (1BE), and multiple brief exposures (5BE). Animals were anesthetized with 1.5 isoflurane for 4 hours, 2 hours, or 2 hours on 5 consecutive days. Physiological parameters, arterial blood gases(ABGs), and metabolic parameters were measured. Expression of tight junction proteins (CL-5, occludin and ZO-1) were measured by RT-qPCR, western blot, andimmunohistochemistry, while BBB permeability was measured by FITC -dextranextravasation at 4 and 24 hours following anesthesia exposure.Results: All physiological, ABG, and metabolic parameters were within normalreference values. A single prolonged exposure to isoflurane showed a significantdecrease in CL-5 levels at 4 hours with full recovery by 24 hours, while occludin levels were significantly reduced at both 4 and 24 hours by western blot andimmunohistochemistry analysis. Dextran extravasation was significant at both 4 and 24 hours following exposure. No changes in BBB structure or function were noted following a single brief exposure. Following 5 BEs to isoflurane, protein levels of occludin were significantly reduced at 4 hours but showed partial recovery at 24 hours. The amount of ZO-1 located at tight junctions was significantly decreased at both 4 and 24 hours. Loss
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 12, 2018
- Accession Number
- AD1128464
Entities
People
- John N. Litchfield
Organizations
- Uniformed Services University of the Health Sciences