CSF smooth-muscle constrictor activity associated with cerebral vasospasm and mortality in SAH patients

Kaye, Andrew H.; Tagari, Philip; Teddy, Peter J.; Adams, C. B. T.; Blaso, William P.; Boullin, D. J.

doi:10.3171/jns.1984.60.5.0927

Cited by 27 publications

(4 citation statements)

References 33 publications

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“…Thus, it appears that a combination of oxidative stress and high bilirubin are required to produce BOXes, which in turn produce SAH-induced vasospasm. This multifactorial requirement (for increased oxidative stress and increased bilirubin) being necessary for BOXes production and the induction of vasospasm is consistent with the published data, suggesting that multiple factors may contribute to SAH-induced cerebral vasospasm (Dietrich and Dacey, 2000;Janjua and Mayer, 2003;Kaye et al, 1984;Lanterna et al, 2005;Macdonald et al, , 2004Weir, 1991, 1994;Pluta, 2005;Sobey and Faraci, 1998;Zimmermann and Seifert, 1998).…”

Section: Boxes Concentration In Patients-preliminary Datasupporting

confidence: 89%

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

Clark

Sharp

2006

J Cereb Blood Flow Metab

111

110

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Many factors have been postulated to cause delayed subarachnoid hemorrhage (SAH)-induced vasospasm, including hemoglobin, nitric oxide, endothelin, and free radicals. We propose that free radicals (because of the high levels that are produced in the blood clots surrounding blood vessels after SAH) act on bilirubin, biliverdin, and possibly heme to produce BOXes (Bilirubin OXidized Products). Bilirubin oxidation products act on vascular smooth muscle cells to produce chronic vasoconstriction and vasospasm combined with a vasculopathy because of smooth muscle cell injury. This review summarizes recent evidence that BOXes play a role in SAH-induced vasospasm. The data supporting a role for BOXes includes (1) identification of molecules in cerebrospinal fluid (CSF) of patients with vasospasm after SAH that have structures consistent with BOXes; (2) BOXes are vasoactive in vitro and mimic the biochemical actions of CSF of patients with vasospasm; (3) BOXes are vasoactive in vivo, constricting rat cerebral vessels; and (4) there is a correlation between clinical occurrence of vasospasm and BOXes concentration in our preliminary study of patients with SAH. Since oxidation of bilirubin, biliverdin, and perhaps heme is proposed to produce BOXes that contribute to vasospasm, either blocking bilirubin formation, inactivating bilirubin or BOXes, or removing all of the blood clot before vasospasm are potential treatment targets.

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Section: Boxes Concentration In Patients-preliminary Datasupporting

confidence: 89%

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

Clark

Sharp

2006

J Cereb Blood Flow Metab

111

110

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“…CSF from patients with SAH does contain smooth muscle constriction activity. 40 When it occurs late in the course of SAH, this activity may be associated with plasmin derived from clot lysis and tissue repair. 37 The functional consequences of loss of neurogenic control is difficult to assess as little is known about this in monkeys.…”

Section: Discussionmentioning

confidence: 99%

Functional arterial changes in chronic cerebrovasospasm in monkeys: an in vitro assessment of the contribution to arterial narrowing.

Bevan¹,

Bevan²,

Frazee³

1987

Stroke

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Cerebral arteries from monkeys with chronic cerebral vasospasm arising from experimental subarachnoid hemorrhage produced 5-6 days previously were examined for changes in their functional properties in an attempt to understand the basis of the narrowing. Hemorrhage was caused by puncture of the internal carotid artery just proximal to the cirde of Willis. Segments taken close to the origins of the anterior and middle cerebral arteries consistently showed decreased extensibility. In addition, they exhibited large, prolonged, spontaneous increases in muscle tone. Other alterations observed include a marked reduction in the capacity of the vessel wall to contract, reduction in constrictor and dilator nerve influences on vascular tone, and some increased sensitivity to serotonin. Small pial arteries (150-200 urn o.d.) from the side of the injury showed large spontaneous irregular increases in tone. It is proposed that 5-6 days after experimental subarachnoid hemorrhage in monkeys the change most responsible for persistent narrowing in the larger arteries is an increased rigidity of the vessel wall. This is probably caused by an inflammatory response. In the smaller arteries, abnormal spontaneous contractile activity is a major factor in narrowing. This activity is not stretch-dependent. We suggest that the Initial cause of the arterial narrowing after hemorrhage is the action of vasoactive substances released in the close vicinity of the arterial wall, which lead to tissue damage, abnormal tone, and an inflammatory response with flbrosis. (Stroke 1987;18:472-481)

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“…Our study focuses on the late pathophysiological changes associated with delayed CV, which occurs as a severe complication of SAH. The prolonged CV as a predictive factor in ischemia-related clinical syndrome [37] most often occurs on the third day and lasts until 14 days after the onset of SAH. In autologous blood injection rat models, a strong contraction of major arteries was seen between 2 and 7 days with a peak on day 5 after the injection, [38].…”

Section: Discussionmentioning

confidence: 99%

Subarachnoid Hemorrhage Depletes Calcitonin Gene-Related Peptide Levels of Trigeminal Neurons in Rat Dura Mater

Masood,

Lakatos,

Kis

et al. 2024

Cells

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Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing.

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CSF smooth-muscle constrictor activity associated with cerebral vasospasm and mortality in SAH patients

Cited by 27 publications

References 33 publications

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

Functional arterial changes in chronic cerebrovasospasm in monkeys: an in vitro assessment of the contribution to arterial narrowing.

Subarachnoid Hemorrhage Depletes Calcitonin Gene-Related Peptide Levels of Trigeminal Neurons in Rat Dura Mater

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