Complement C1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia.
Recent evidence suggests that the pathophysiology of neurodegenerative and inflammatory neurological diseases has a neuroimmunological component involving complement, an innate humoral immune defense system. The present study demonstrates the effects of experimentally induced global ischemia on the biosynthesis of C1q, the recognition subcomponent of the classical complement activation pathway, in the CNS. Using semiquantitative in situ hybridization, immunohistochemistry, and confocal laser scanning microscopy, a dramatic and widespread increase of C1q biosynthesis in rat brain microglia (but not in astrocytes or neurons) within 24 h after the ischemic insult was observed. A marked increase of C1q functional activity in cerebrospinal fluid taken 1, 24, and 72 h after the ischemic insult was determined by C1q-dependent hemolytic assay. In the light of the well-established role of complement and complement activation products in the initiation and maintenance of inflammation, the ischemia-induced increase of cerebral C1q biosynthesis and of C1q functional activity in the cerebrospinal fluid implies that the proinflammatory activities of locally produced complement are likely to contribute to the pathophysiology of cerebral ischemia. Pharmacological modulation of complement activation in the brain may be a therapeutic target in the treatment of stroke.
Schäfer
M K
MK
Department of Anatomy, University of Marburg, Marburg, Germany.
Schwaeble
W J
WJ
Post
C
C
Salvati
P
P
Calabresi
M
M
Sim
R B
RB
Petry
F
F
Loos
M
M
Weihe
E
E
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D015922:Complement C1q / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000235:genetics; D004076:Digoxigenin; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015347:RNA Probes; D018075:RNA, Complementary; D051381:Rats; D017208:Rats, Wistar; D013462:Sulfur Radioisotopes; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D015347:RNA Probes; D018075:RNA, Complementary; D013462:Sulfur Radioisotopes; D015922:Complement C1q; D004076:Digoxigenin