Premium
Glial responses, clusterin, and complement in permanent focal cerebral ischemia in the mouse
Author(s) -
Van Beek Johan,
Chan Philippe,
Bernaudin Myriam,
Petit Edwige,
MacKenzie Eric T.,
Fontaine Marc
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(200007)31:1<39::aid-glia40>3.0.co;2-1
Subject(s) - clusterin , biology , ischemia , in situ hybridization , glial fibrillary acidic protein , pathology , microglia , immunostaining , middle cerebral artery , cerebral cortex , astrocyte , immunohistochemistry , inflammation , immunology , central nervous system , gene expression , neuroscience , medicine , apoptosis , biochemistry , gene
There is considerable evidence that complement activation occurs within the CNS in inflammatory and degenerative disorders, but little is known about its involvement in the pathophysiology of cerebral ischemia. Our study sought to characterize the glial response and the expression of complement factors after permanent focal cerebral ischemia in the mouse, using semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR), in situ hybridization, and immunohistochemistry. mRNA expression of glial fibrillary acidic protein (GFAP) increased at day 1 and peaked 3 days after middle cerebral artery (MCA) occlusion in the perifocal area. Immunohistochemical staining for GFAP indicated that astroglia were activated the day after MCA occlusion. Microglial activation, as assessed by lectin‐binding experiments, increased by 1 day after MCA occlusion in the perifocal area and peaked at 3 days postocclusion. RT‐PCR experiments demonstrated an increased expression of clusterin, C1qB, and C4 mRNA in the ischemic cortex, with a peak level at 3 days after MCA occlusion. Clusterin, C1qB, and C4 mRNA were located in the perifocal area, as assessed by in situ hybridization. Reactive astrocytes within the cortex medial to the ischemic lesion were found to be strongly immunoreactive for clusterin. In addition, we observed C1q‐positive macrophage‐like cells within the infarcted core at 3 days postocclusion. At 7 days after the onset of ischemia, increased C4 immunostaining was restricted to perifocal neurons. We conclude that local expression of complement components may contribute to the inflammation observed in this model, thereby representing an important process in secondary injury mechanisms after focal cerebral ischemia. GLIA 31:39–50, 2000. © 2000 Wiley‐Liss, Inc.