Complement C1q is dramatically up-regulated in brain microglia in responseto transient global cerebral ischemia

Recent evidence suggests that the pathophysiology of neurodegenerative and inflammatory neurological diseases has a neuroimmunological component invol ving complement, an innate humoral immune defense system. The present study demonstrates the effects of experimentally induced global ischemia on the biosynthesis of Clq, the recognition subcomponent of the classical compleme nt activation pathway, in the CNS. Using semiquantitative in situ hybridiza tion, immunohistochemistry, and confocal laser scanning microscopy, a drama tic and widespread increase of Clq biosynthesis in rat brain microglia (but not in astrocytes or neurons) within 24 h after the ischemic insult was ob served, A marked increase of Clq functional activity in cerebrospinal fluid taken 1, 24, and 72 h after the ischemic insult was determined by Clq-depe ndent hemolytic assay. In the light of the well-established role of complem ent and complement activation products in the initiation and maintenance of inflammation, the ischemia-induced increase of cerebral Clq biosynthesis a nd of Clq functional activity in the cerebrospinal fluid implies that the p roinflammatory activities of locally produced complement are likely to cont ribute to the pathophysiology of cerebral ischemia, Pharmacological modulat ion of complement activation in the brain may be a therapeutic target in th e treatment of stroke.