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Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller Jan 2013

Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller

Anatomy and Neurobiology Publications

Background

Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.

Methods

To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent …


Glia And Epilepsy: Excitability And Inflammation, Orrin Devinsky, Annamaria Vezzani, Souhel Najjar, Nihal C. De Lanerolle, Michael A. Rogawski Dec 2012

Glia And Epilepsy: Excitability And Inflammation, Orrin Devinsky, Annamaria Vezzani, Souhel Najjar, Nihal C. De Lanerolle, Michael A. Rogawski

Michael A. Rogawski

Epilepsy is characterized by recurrent spontaneous seizures due to hyperexcitability and hypersynchrony of brain neurons. Current theories of pathophysiology stress neuronal dysfunction and damage, and aberrant connections as relevant factors. Most antiepileptic drugs target neuronal mechanisms. However, nearly one-third of patients have seizures that are refractory to available medications; a deeper understanding of mechanisms may be required to conceive more effective therapies. Recent studies point to a significant contribution by nonneuronal cells, the glia – especially astrocytes and microglia – in the pathophysiology of epilepsy. This review critically evaluates the role of glia-induced hyperexcitability and inflammation in epilepsy.