Neuropharmacologic Approaches to Restore the Brain's Microenvironment

J Neuroimmune Pharmacol. 2016 Sep;11(3):484-94. doi: 10.1007/s11481-016-9686-5. Epub 2016 Jun 28.

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.

Keywords: Alzheimer’s disease; Astrocytes; Human immunodeficiency virus-associated neurocognitive disorders; Microglia; Neurodegenerative disorders; Neuroinflammation; Parkinson’s disease.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism*
  • Brain / pathology
  • Cellular Microenvironment / drug effects*
  • Cellular Microenvironment / physiology
  • Central Nervous System Agents / pharmacology
  • Central Nervous System Agents / therapeutic use
  • Genetic Therapy / methods
  • Genetic Therapy / trends
  • Humans
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology

Substances

  • Central Nervous System Agents