Trends in Pharmacological Sciences
OpinionCerebral vasospasm: looking beyond vasoconstriction
Section snippets
Cerebral vasospasm: a deadly contraction of smooth muscle
Spontaneous subarachnoid hemorrhage (SAH) arising from the rupture of an intracranial aneurysm (see Glossary) is a multiphasic disease [1]. Presentation ranges from simple sudden-onset headache to the patient requiring ventilatory assistance to ensure survival, to the patient dying before arrival at hospital. After this initial crisis, another can occur four or five days later: a syndrome labeled cerebral vasospasm (Table 1) because of its association with angiographic narrowing of cerebral
Achieving vascular dilatation but failing to improve outcome
Consistent with the classical idea of arterial narrowing being the hallmark of cerebral vasospasm, a long-awaited powerful vasodilator arrived in the form of clazosentan, an antagonist to the endogenous peptide vasoconstrictor endothelin [7]. A double-blind, randomized clinical trial of clazosentan showed a dose-dependent 65% reduction in the relative risk of angiographic vasospasm in patients treated with the highest drug dose [8]. Despite this, there was only a small reduction in the number
Classical ideas regarding the contraction of vascular smooth muscle cells in cerebral vasospasm
The essence of the clazosentan study [8] is not that it is yet another drug that fails to challenge cerebral vasospasm in the clinical setting. The true implication of this study could be that the basic pathological process of cerebral vasospasm is not understood at all or, more specifically, that the simple sequence of SAH leading to angiographic narrowing of arteries, leading to ischemia and poor outcome is not so simple after all. If this were true, a long-term beneficial effect would have
New frontiers – pre-SAH and pre-vasospasm research
There have been major developments in research into the phase preceding vasospasm, including recognition of the early events after SAH such as increased intracranial pressure [23], disruption of the blood–brain barrier (BBB), global cerebral ischemia [24], inflammation [25] and cortical spreading depression [26]. Because all of these events are directly or indirectly related to and/or evoked by the presence of arterial blood clots in the subarachnoid space, they could be equally as responsible
Concluding remarks
The emerging consensus among researchers in the field is that future efforts must concentrate on all consequences of SAH, how they relate to each other and how they lead to delayed cerebral ischemia. The treatment efforts in the past 50 years, targeting only the reversal or prevention of cerebral vasospasm, might not be enough to achieve a better outcome from delayed cerebral ischemia because pre-vasospasm factors such as intracranial pressure, BBB breakdown, brain edema, inflammation, cell
Glossary
- Cortical spreading depression
- a non-physiological global depolarization of the cerebral cortex that can be initiated by a given stimulus. The phenomenon propagates across the cerebral cortex at a rate of 2–5 mm min−1 and is accompanied by transient marked changes in cerebral blood flow, local tissue oxygen tension and, probably, metabolic rate.
- Intracranial aneurysm
- localized blood-filled dilatation of one of the major cerebral arteries. The aneurysm is often dome shaped. Its walls are thin, making
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Cited by (108)
Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage – Serum D-dimer and C-reactive Protein as Early Markers
2020, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :The etiopathogenesis of vasospasm (VS) and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is still incompletely understood. Apart from VS, a variety of mechanisms have been shown to contribute to the multi-causal chain reaction that leads to the development of DCI.1-3 In the past, inflammatory processes were shown to play a role in the rupture of aneurysms and the development of VS.4-6 Procalcitonin is a rather specific parameter for detecting infections and for differentiating between sepsis and noninfectious systemic inflammatory response syndrome other than white blood count (WBC) and C-reactive protein (CRP), which can be elevated during different kinds of inflammatory processes.7-9
Carbon monoxide attenuates vasospasm and improves neurobehavioral function after subarachnoid hemorrhage
2019, Archives of Biochemistry and BiophysicsCitation Excerpt :Delayed neurologic deterioration from vasospasm remains the greatest cause of death and disability after SAH [8,9]. Cerebral vasospasms occur in more than one-half of all patients with SAH and they are recognized as the main cause of delayed cerebral ischemia after SAH [10–12]. This condition normally advances between 4 and 14d and the most severe conditions are observed between 7 and 9d after SAH [13].
Low Glasgow Coma Score in Traumatic Intracranial Hemorrhage Predicts Development of Cerebral Vasospasm
2018, World NeurosurgeryCitation Excerpt :However, the incidence and the exact mechanism by which post-traumatic vasospasm (PTV) occurs remain unknown. Several mechanisms have proposed, including the physical stretching of vessels causing vasospasm,1-3 dysregulation of calcium, upregulation of endothelin-I,4 and an apoptotic/inflammatory pathway activated by global ischemia and/or disruption of the blood–brain barrier.5 Furthermore, much of the literature examining PTV includes a mixed patient population in which vasospasm has been identified using transcranial Doppler (TCD), computed tomography (CT) angiography, or to a much lesser, extent digital subtraction angiography (DSA).
The impact of pre-ictal statin use on vasospasm and outcome in aneurysmal subarachnoid hemorrhage
2023, Acta Neurochirurgica