Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro.
BACKGROUND
Blood-brain barrier (BBB) disruption after stroke can worsen ischemic injury by increasing edema and causing hemorrhage. We determined the effect of microglia on the BBB and its primary constituents, endothelial cells (ECs) and astrocytes, after ischemia using in vivo and in vitro models.


RESULTS
Primary astrocytes, ECs, or cocultures were prepared with or without added microglia. Primary ECs were more resistant to oxygen-glucose deprivation/reperfusion than astrocytes. ECs plus astrocytes showed intermediate vulnerability. Microglia added to cocultures nearly doubled cell death. This increase was prevented by minocycline and apocynin. In vivo, minocycline reduced infarct volume and neurological deficits and markedly reduced BBB disruption and hemorrhage in mice after experimental stroke.


CONCLUSIONS
Inhibition of microglial activation may protect the brain after ischemic stroke by improving BBB viability and integrity. Microglial inhibitors may prove to be an important treatment adjunct to fibrinolysis.
Department of Neurology, University of California, San Francisco Veterans Affairs Medical Center, California 94121, USA. yenari@alum.mit.edu
Midori A
MA
Yenari
Lijun
L
Xu
Xian Nan
XN
Tang
Yanli
Y
Qiao
Rona G
RG
Giffard
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000473:pathology; D005947:Glucose / Q000172:deficiency; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology*; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000098:Acetophenones; D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C056165:acetovanillone; D006861:Hydrogen Peroxide; D008911:Minocycline; D005947:Glucose