Microglial activation and intracerebral hemorrhage.
BACKGROUND
Microglia activate upon injury, migrate to the injury site, proliferate locally, undergo morphological and gene expression changes, and phagocytose injured and dying cells. Cytokines and proteases secreted by these cells contribute to the injury and edema formed. We studied the injury outcome after local elimination/paralysis of microglia.


METHODS
Adult male mice were subjected to intracerebral hemorrhage (ICH) by intra-caudate injection of either collagenase or autologous blood. Mice survived for different periods of time, and were subsequently evaluated for neurological deficits, size of the hematoma, and microglia activation. Mice expressing an fms-GFP transgene or the CD11b-HSVTK transgene were also used. For elimination of monocytes/macrophages, CD11b-HSVTK mice were treated with ganciclovir prior to hemorrhage. Modifiers of microglial activation were also used.


RESULTS
Induction of ICH resulted in robust microglia activation and recruitment of macrophages. Inactivation of these cells, genetically or pharmacologically, pointed to a critical role of the time of such inactivation, indicating that their role is distinct at different time points following injury. Edema formation is decreased when microglia activation is inhibited, and neurological outcomes are improved.


CONCLUSIONS
Microglia, as immunomodulatory cells, have the ability to modify the final presentation of ICH.
Gao
Z
Z
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794-8651, USA.
Wang
J
J
Thiex
R
R
Rogove
A D
AD
Heppner
F L
FL
Tsirka
S E
SE
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001929:Brain Edema; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D017364:Collagenases; D004195:Disease Models, Animal; D015774:Ganciclovir / Q000627:therapeutic use; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology; D009460:Neurologic Examination; D013997:Time Factors
C491049:Aif1 protein, mouse; D000943:Antigens, Differentiation; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; C036763:monocyte-macrophage differentiation antigen; D049452:Green Fluorescent Proteins; D017364:Collagenases; D015774:Ganciclovir