Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms.
Peritumoral brain edema (PTBE) is mediated by blood-brain barrier breakdown. PTBE results from interstitial vasogenic brain edema due to vascular endothelial growth factor and other inflammatory products of brain tumors. Glucocorticoids (GCs) are the mainstay for treatment of PTBE despite significant systemic side effects. GCs are thought to affect multiple cell types in the edematous brain. Here, we review preclinical studies of GC effects on edematous brain and review mechanisms underlying GC action on tumor cells, endothelial cells, and astrocytes. GCs may reduce tumor cell viability and suppress vascular endothelial growth factor (VEGF) production in tumor cells. Modulation of expression and distribution of tight junction proteins occludin, claudin-5, and ZO-1 in endothelial cells likely plays a central role in GC action on endothelial cells. GCs may also have an effect on astrocyte angiopoietin production and limited effect on astrocyte aquaporin. A better understanding of these molecular mechanisms may lead to the development of novel therapeutics for management of PTBE with a better side effect profile.
Surgical Neurology Branch, Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Diseases and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD, 20892-1414, USA.
Roger
http://orcid.org/0000-0002-6229-7546
R
Murayi
Surgical Neurology Branch, Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Diseases and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD, 20892-1414, USA. Prashant.Chittiboina@nih.gov.
Prashant
P
Chittiboina
D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology*; D001932:Brain Neoplasms / Q000150:complications*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans
D005938:Glucocorticoids
Blood-brain barrier; Glucocorticoids; Peritumoral brain edema (PTBE)