title: Neuropharmacologic Approaches to Restore the Brain's Microenvironment.
abstract: Maintaining the central nervous system microenvironment after injury, infection, inflammatory and degenerative diseases is contingent upon adequate control of glial homeostatic functions. Disease is caused by microbial, environmental and endogenous factors that compromise ongoing nervous system functions. The final result is neuronal injury, dropout and nerve connection loss, and these underlie the pathobiology of Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, stroke, and bacterial, parasitic and viral infections. However, what promotes disease are homeostatic changes in the brain's microenvironment affected by innate glial immune pro-inflammatory and adaptive immune responses. These events disturb the brain's metabolic activities and communication abilities. How the process affects the brain's regulatory functions that can be harnessed for therapeutic gain is the subject at hand. Specific examples are provided that serve to modulate inflammation and improve disease outcomes specifically for HIV-associated neurocognitive disorders.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Weizhe
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Public Health Sciences, Environmental Health Laboratory, University of Hawaii at Manoa, Honolulu, HI, 96822, USA.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Tong
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Larisa Y
authors.initials: LY
authors.lastname: Poluektova
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA. hegendel@unmc.edu.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.affiliation: Department of Public Health Sciences, Environmental Health Laboratory, University of Hawaii at Manoa, Honolulu, HI, 96822, USA. yuanan@hawaii.edu.
authors.forename: Yuanan
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D060833:Cellular Microenvironment / Q000187:drug effects* / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D002491:Central Nervous System Agents
keywords: Alzheimer’s disease; Astrocytes; Human immunodeficiency virus-associated neurocognitive disorders; Microglia; Neurodegenerative disorders; Neuroinflammation; Parkinson’s disease