Neutralization of Interleukin-1β Reduces Vasospasm and Alters Cerebral Blood Vessel Density Following Experimental Subarachnoid Hemorrhage in Rats

Abstract

Subarachnoid hemorrhage (SAH) develops when extravasated arterial blood enters subarachnoid space and mixes with cerebrospinal fluid. As a result, many pathologies develop, including arterial vasospasm that leads to the ischemia and hypoxia. Immuno-inflammatory response is considered as the cause of numerous complications following SAH. In the study, we examined the role of one of major cytokines, interleukin 1-beta (IL-1beta), on the vascular pathologies after experimental SAH in adult rats. SAH was produced by injection of 150 uL of autologous arterial blood into cisterna magna. In 50% of animals, IL-1beta activity was inhibited by intracerebroventricular administration of anti-rat IL-1beta antibodies (SAH' groups). Control group consisted of sham-operated rats. Ninety minutes or 24 hrs following surgery, animals were perfused transcardially and whole brains were collected. Spasm index (ratio of vessel diameter to the mean wall thickness) of basilar artery as well as blood vessel density (number of vessels per square millimeter) at brain stem and frontal part of the brain were measured. SAH led to the vasospasm of basilar artery and increased the density of blood vessel. Neutralization of IL-1beta activity significantly reduced both the vasospasm and blood vessel density only 24 hrs after SAH. The results demonstrate an important role of IL-1beta in the delayed development of vascular pathologies after subarachnoid hemorrhage.

Ferrous Chelator 2,2′-Dipyridyl Attenuates Cerebral Vasospasm after Experimental Subarachnoid Haemorrhage in Rabbits

“…The mean ± SE vasospasm index (ratio of the arterial luminal area to the arterial wall thickness 19,20 ) was 32.7 ± 3.5 in the control group, 6.26 ± 0.6 in the SAH group, 7.15 ± 0.7 in the SAH + DMSO group and 24.46 ± 2.6 in the SAH + DP group (Fig. 2D).…”

Recombinant interleukin-1ß dilates steelhead trout coronary microvessels: effect of temperature and role of the endothelium, nitric oxide and prostaglandins

“…However, it is unclear what the effect of long-term exposure to this cytokine would have on trout coronary tone and blood flow. Long-term treatment with IL-1β induced vasospastic responses in the coronary vessels of pigs (Shimokawa et al, 1996) and there is a growing body of evidence that links IL-1β with reduced cerebral blood flow in mammals (Proescholdt et al, 2002;Maher et al, 2003;Jedrzejowska-Szypulka et al, 2009). This dependence of the vasoactive effects of IL-1β on time of exposure is not surprising given the broad spectrum of activities of this cytokine, and that many of its downstream actions occur over a prolonged period and involve other vasoactive substances such as IL-6 and endothelin-1 (Maher et al, 2003;Jedrzejowska-Szypulka et al, 2009).…”

“…There is evidence that IL-1β induces the production and/or release of vasoactive substances such as prostaglandins (PGs) and nitric oxide (NO) from mammalian vascular cells (Rossi et al, 1985;Hirafuji et al, 2002;Proescholdt et al, 2002;Schiltz and Sawchenko, 2002;Jedrzejowska-Szypulka et al, 2009). However, the results of experiments investigating the role of these two biological agents in modulating vascular resistance have been quite variable.…”

“…However, in the canine basilar artery (McKean et al, 1994), human vascular smooth muscle cells (Beasley and McGuiggin, 1995) and isolated rabbit mesenteric arteries (Marceau et al, 1991), IL-1β induces the release of cyclooxygenase 2 (COX-2), a key enzyme in the catalytic conversion of arachidonic acid to PGs, but not NO. Furthermore, a positive-feedback mechanism has been suggested for human endothelial and vascular smooth muscle (VSM) cells (Warner et al, 1987a,b;Proescholdt et al, 2002), where IL-1β stimulates the synthesis of more IL-1β, and induces the production and release of other vasoactive agents such as endothelin-1 (Jedrzejowska-Szypulka et al, 2009) and serotonin (Chiu et al, 1995).…”

A case of fatal late vasospasm in a patient with a recurrent, supratentorial, rhabdoid primitive neuroectodermal tumor: possible molecular implications.

“…These cytokines have been reliably detected in the cerebrospinal fluid and microdialysate from patients with SAH, and they were associated with vasospasm (evidenced by transcranial Doppler ultrasound), poor outcome, and ischemic deficits (6,9,(10)(11)(12)18,20).…”