Cerebrovascular inflammation following subarachnoid hemorrhage.
Aneurysmal subarachnoid hemorrhage frequently results in complications including intracranial hypertension, rebleeding and vasospasm. The extravasated blood is responsible for a cascade of reactions involving release of various vasoactive and pro-inflammatory factors (several of which are purported to induce vasospasm) from blood and vascular components in the subarachnoid space. The authors review the available evidence linking these factors to the development of inflammatory lesions of the cerebral vasculature, emphasizing: 1) neurogenic inflammation due to massive release of sensory nerve neuropeptides; 2) hemoglobin from lysed erythrocytes, which creates functional lesions of endothelial and smooth muscle cells; 3) activity, expression and metabolites of lipoxygenases cyclooxygenases and nitric oxide synthases; 4) the possible role of endothelin-1 as a pro-inflammatory agent; 5) serotonin, histamine and bradykinin which are especially involved in blood-brain barrier disruption; 6) the prothrombotic and pro-inflammatory action of complement and thrombin towards endothelium; 7) the multiple actions of activated platelets, including platelet-derived growth factor production; 8) the presence of perivascular and intramural macrophages and granulocytes and their interaction with adhesion molecules; 9) the evolution, origins, and effects of pro-inflammatory cytokines, especially IL-1, TNF-alpha and IL-6. Human and animal studies on the use of anti-inflammatory agents in subarachnoid hemorrhage include superoxide and other radical scavengers, lipid peroxidation inhibitors, iron chelators, NSAIDs, glucocorticoids, and serine protease inhibitors. Many animal studies claim reduced vasospasm, but these effects are not always confirmed in human trials, where symptomatic vasospasm and outcome are the major endpoints. Despite recent work on penetrating vessel constriction, there is a paucity of studies on inflammatory markers in the microcirculation.
Sercombe
Richard
R
Laboratoire de Recherches Cérébrovasculaires, CNRS UPR 646, IFR Circulation Lariboisière, Université Paris VI, Faculté de Médecine Lariboisière-St Louis, Paris, France. sercombe@ext.jussieu.fr
Dinh
Yves R Tran
YR
Gomis
Philippe
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002536:Cerebral Arteries / Q000293:injuries / Q000473:pathology; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D006801:Humans; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology; D014657:Vasculitis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology
D000893:Anti-Inflammatory Agents