Cerebral vasospasm is the prolonged, intense vasoconstriction of the larger conducting arteries in the subarachnoid space which is initially surrounded by a clot. Significant narrowing of the blood vessels in the brain develops gradually over the first few days after the aneurysmal rupture. This kind of narrowing usually is maximal in about a week's time following intracerebral haemorrhage. Vasospasm is one of the leading causes of death after the aneurysmal rupture along with the effect of the initial haemorrhage and later bleeding.

Cerebral vasospasm is a common and severe complication following aneurysmal subarachnoid hemorrhage, occurring in 50-90% of cases after aneurysm rupture. Moderate or severe vasospasm in one or more cerebral arteries develops in approximately two-thirds of patients with ruptured aneurysms. Of these, nearly half exhibit symptoms of cerebral ischemia. Infarction occurs in about half of the symptomatic patients and is significantly associated with factors such as advanced age, a history of hypertension, or diabetes mellitus. Despite improvements in the management of subarachnoid hemorrhage, the overall risk of death and disability remains approximately 10%.

The pathogenesis of cerebral vasospasm, particularly after subarachnoid hemorrhage, is complex and is thought to involve several mechanisms that lead to the narrowing of cerebral arteries, reducing blood flow to the brain. Currently understood mechanisms of vasospasm are as follows:

When an aneurysm ruptures, blood enters the subarachnoid space, forming clots. Hemoglobin, released from these clots, plays a key role in initiating vasospasm. Hemoglobin scavenges nitric oxide, a critical vasodilator produced by the endothelium (the inner lining of blood vessels). The loss of nitric oxide leads to unopposed contraction of smooth muscle cells in the vessel wall, resulting in acute vasoconstriction. This process is calcium-dependent and represents the early, more reversible stage of vasospasm.

Endothelial cells regulate vascular tone by producing vasodilators (like nitric oxide and prostacyclin) and vasoconstrictors (like endothelin). In vasospasm, endothelial damage disrupts this balance, reducing vasodilator production while increasing levels of vasoconstrictors. Elevated levels of endothelin, a potent vasoconstrictor, are consistently observed in patients with vasospasm, contributing to prolonged and sustained narrowing of the arteries.

While early vasospasm is largely mediated by functional changes in smooth muscle contraction, chronic vasospasm involves more permanent structural damage to the vessel wall. In chronic stages, smooth muscle contraction becomes less reversible because of remodeling and damage to the layers of the blood vessels. This damage impairs normal vessel function and leads to sustained vasoconstriction.

Blood in the subarachnoid space triggers an inflammatory response, which includes the release of cytokines, leukocyte infiltration, and activation of microglia. This inflammation contributes to oxidative stress, further damaging the endothelial lining and smooth muscle cells. The inflammatory response exacerbates the release of vasoconstrictors like endothelin and decreases the availability of vasodilators like nitrous oxide, worsening vasospasm.

The smooth muscle contraction in vasospasm is heavily dependent on calcium signaling. During acute vasospasm, calcium influx into smooth muscle cells causes contraction. In chronic vasospasm, alterations in calcium-handling mechanisms in vascular smooth muscle cells may contribute to persistent vasoconstriction that does not respond to traditional vasodilatory signals.