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.