In gratitude of the loyal support of our members, the CNS is offering complimentary 2021 Annual Meeting registration to all members! Learn more.

  • Expression of the Pro-Inflammatory Cytokine IL-1b in a Murine Transgenic Haptoglobin Model of SAH

    Final Number:
    1088

    Authors:
    Gustavo Pradilla MD; Tomas Garzon-Muvdi MD MS.; Matthew Bender; Robert Thomas Wicks BS, BA; Jacob Ruzevick BS; Carlos Pardo-Villamizar; Rafael J. Tamargo MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Inflammation plays a critical role in the pathogenesis of vasospasm after aneurysmal subarachnoid hemorrhage(aSAH). The Hp2-2 genotype appears to be pro-inflammatory, and predisposes to symptomatic vasospasm. IL-1b is a pro-inflammatory cytokine released by macrophages and monocytes, which acts through distinct pathways to promote inflammatory cell recruitment. We generated transgenic Hp2-2 mice and measured IL1b expression, before and 24hours post-SAH and compared it to the expression of wild type(Hp1-1) mice.

    Methods: Transgenic C57Bl6-Hp2-2 mice were developed and expanded in colony; wild-type Hp1-1 animals were used for comparison. Animals were randomized to 3 groups per genotype: no-interventions (baseline, n=5), surgery-without-SAH (n=10), or surgery+SAH (n=10) and were perfused/euthanized 24-hours post-SAH. The common carotid artery(CCA), femoral artery(FA), olfactory bulbs(OB), forebrain(FB), caudate/putamen(C/P), brainstem/basilar artery(BS/BA), and cerebellum(CER) were processed for proteomic analysis(mouse cytokine array system, Bioplex23plex, Bio-Rad, Minneapolis,MN)

    Results: At baseline, IL-1b was higher in Hp2-2s than in Hp1-1s in the OB(2.89±0.10 vs. 0.66±0.01), C/P(1.03±0.08 vs. 0.92±0.10), and CER(1.06±0.08 vs. 0.98±0.13) and lower in the CCA(1.06±0.06 vs. 2.09±0.27), FA(0.80±0.13 vs. 2.61±0.13), BS/BA(0.12±0.0 vs. 0.88±0.10), and FB(0.21±0.02 vs. 0.47±0.03). After surgery without SAH, IL-1b levels were higher in Hp2-2 than in Hp1-1 animals in the CCA(2.74±0.25 vs. 0.17±0.00), FA(3.23±0.25 vs. 2.32±0.09), BS/BA (0.82±0.04 vs. 0.81±0.09), FB(0.66±0.04 vs. 0.15±0.01), and C/P(5.18±0.38 vs. 0.46±0.07) and lower in the OB(0.71±0.00 vs. 0.80±0.03) and CER(0.41±0.04 vs. 0.50±0.04). After SAH, IL-1b was higher in Hp2-2 animals in FA (1.52±0.21 vs. 1.33±0.12) and OB (0.52±0.02 vs. 0.00±0.00) and lower in CCA (0.73±0.09 vs. 0.88±0.24) and BS/BA (0.21±0.01 vs. 0.34±0.03). Data were not available for FB, C/P, and CER.

    Conclusions: Hp2-2 genotype is associated with lower baseline IL-1b levels that increase after surgery with/without SAH when compared to Hp1-1 mice. Findings suggest that IL-1b contributes to inflammation after SAH, and that its activity is more pronounced in animals with an Hp2-2 genotype in this model.

    Patient Care: IL-1b constitutes a potential target in the treatment of patients with aneurysmal SAH

    Learning Objectives: To understand the role of IL-1b in the pathogenesis of cerebral vasospasm. To determine differences in IL-1b expression in animals with different haptoglobin genotypes.

    References:

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy