University of Kentucky
The Effects of Morphine on the Blood Brain Barrier: An In vitro Study
Institution
University of Kentucky
Faculty Advisor/ Mentor
Gilson Capilouto; Michael Nonnemacher; Brian Wigdahl
Abstract
HIV-1 infects T-cells and monocytes of the immune system making it difficult for people to fight infections that are not usually problematic. Treatment of those with HIV-1 infections is difficult due to the error-prone nature of the viral reverse transcriptase, and due to the fact that the virus integrates into the host cell genome, creating a chronic infection. In this study,exploring the factors involved in immune cells transmigrating across the blood brain barrier and into the CNS from the periphery in the context of HIV-1 infection and how this relates to HAND(HIVAssociated Neurocognitive Disorders) incidence and severity was observed. This project reveals a mechanism by which morphine, through prolonged exposure, increases blood brain barrier leakiness leading to accelerated HAND. Morphine abuse by human immunodeficiency virus type 1 (HIV-1)-infected individuals leads to an increase in viral replication and peripheral viral load, rapid disease progression and increased incidence and severity of neurocognitive abnormalities compared to non-drug abusers. The blood-brain barrier (BBB) is an obstacle that must be overcome during neuroinvasion with eventual development of HIV-associated neurocognitive disorders (HAND). In thus study, an increase in PBMC transmigration and firm adhesion was observed following prolonged morphine exposure, in the absence of an increase in overall barrier leakiness. This project unravels a mechanism by which morphine disrupts periphery-CNS homeostasis leading to accelerated HAND.
The Effects of Morphine on the Blood Brain Barrier: An In vitro Study
HIV-1 infects T-cells and monocytes of the immune system making it difficult for people to fight infections that are not usually problematic. Treatment of those with HIV-1 infections is difficult due to the error-prone nature of the viral reverse transcriptase, and due to the fact that the virus integrates into the host cell genome, creating a chronic infection. In this study,exploring the factors involved in immune cells transmigrating across the blood brain barrier and into the CNS from the periphery in the context of HIV-1 infection and how this relates to HAND(HIVAssociated Neurocognitive Disorders) incidence and severity was observed. This project reveals a mechanism by which morphine, through prolonged exposure, increases blood brain barrier leakiness leading to accelerated HAND. Morphine abuse by human immunodeficiency virus type 1 (HIV-1)-infected individuals leads to an increase in viral replication and peripheral viral load, rapid disease progression and increased incidence and severity of neurocognitive abnormalities compared to non-drug abusers. The blood-brain barrier (BBB) is an obstacle that must be overcome during neuroinvasion with eventual development of HIV-associated neurocognitive disorders (HAND). In thus study, an increase in PBMC transmigration and firm adhesion was observed following prolonged morphine exposure, in the absence of an increase in overall barrier leakiness. This project unravels a mechanism by which morphine disrupts periphery-CNS homeostasis leading to accelerated HAND.