title: Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats.
abstract: Human C-reactive protein (CRP), the classic acute phase plasma protein, increases in concentration after myocardial infarction and stroke. Human CRP binds to ligands exposed in damaged tissue and can then activate complement and its proinflammatory functions. In contrast, rat CRP, which binds to similar ligands, does not activate complement. In the present study, systemic complement depletion with cobra venom factor in adult rats subjected to middle cerebral artery occlusion did not affect cerebral infarct size, indicating that circulating complement does not contribute to injury in this model. However, we have previously reported that administration of human CRP to rats undergoing coronary artery ligation caused a marked increase in size of the resulting myocardial infarction, associated with codeposition of human CRP and rat complement in the infarcts. In the present study, we show that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin. Human CRP can thus contribute to ischemic tissue damage in the brain as well as in the heart, and inhibition of CRP binding may therefore be a promising target for tissue protective acute therapeutic intervention in stroke as well as in myocardial infarction.
authors.affiliation: F Hoffman-La Roche Ltd, Preclinical CNS Research, Pharmaceuticals Division, Basel, Switzerland.
authors.forename: Ramanjit
authors.initials: R
authors.lastname: Gill
authors.forename: John A
authors.initials: JA
authors.lastname: Kemp
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Mark B
authors.initials: MB
authors.lastname: Pepys
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002097:C-Reactive Protein / Q000633:toxicity*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002097:C-Reactive Protein