Microglia as a Pharmacological Target in Infectious and Inflammatory Diseases of the Brain

Abstract

Following an eclipse of scientific inquiry regarding the biology of microglia that lasted 50 years, recognition toward the end of the 20th century of their neuropathogenic role in HIV-associated dementia and in neuroinflammatory/neurodegenerative diseases fueled a renaissance of interest in these resident macrophages of the brain parenchyma. Results of a large number of in vitro studies, using isolated microglial cells or glial/neuronal cell cultures, and parallel findings emerging from animal models and clinical studies have demonstrated that activated microglia produce a myriad of inflammatory mediators that both serve important defense functions against invading neurotropic pathogens and have been implicated in brain damage in infectious as well as neuroinflammatory/neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review provides a brief background regarding the physiological and pathophysiological roles of microglia and highlights current pharmacological approaches that target activated microglia with the goal of ameliorating infectious and neuroinflammatory/neurodegenerative diseases of the brain. Although this aspect of the field of neuroimmunopharmacology is in its infancy, it holds great promise for developing new treatments and prevention of diseases that are, in many cases, epidemic throughout the world.

Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

“…Microglia are the resident immune cell population of the CNS, comprising 10-15% of the total cell population (for reviews see [24,29,74]). They play important, protective roles in the CNS such as removing pathogens and promoting tissue regeneration after injury.…”

Status Epilepticus Induces a Particular Microglial Activation State Characterized by Enhanced Purinergic Signaling

“…Increasing evidence indicates that inflammation is a landmark for a number of acute and chronic brain disorders, including neuropathologies associated with seizures (Rock and Peterson, 2006;Choi and Koh, 2008). For instance, an increased expression of inflammatory markers has been observed in surgically resected temporal tissues from patients with temporal lobe epilepsy (Sheng et al, 1994;Crespel et al, 2002;Vezzani and Granata, 2005).…”

Anti-inflammatory effects of lipoic acid through inhibition of GSK-3β in lipopolysaccharide-induced BV-2 microglial cells

“…14 Inflammation is closely associated with neurodegenerative diseases, such as AD (McGeer and McGeer 2003), PD (Barcia et al 2003), post traumatic brain injury and brain ischemia (Rock and Peterson 2006). Prolonged activation of microglia by LPS may be directly toxic to neuronal cells because of the significant release of various inflammatory mediators, such as ROS and NO (Banati et al 1993).…”