Immune activation in patients with admission blood pressure above 185/110 mm Hg in acute ischemic stroke

  • Author / Creator
    Batool, Yusra
  • Background: An admission blood pressure over 185/110 mm Hg is associated with increased risk of recombinant tissue plasminogen activator (r-tPA)-related hemorrhagic transformation (HT). Stroke guidelines recommend blood pressure (BP) above 185/110 mm Hg be lowered before r-tPA treatment. How high blood pressure increases blood brain barrier disruption and risk of HT remains poorly understood. We evaluated peripheral leukocyte activation in stroke patients in relation to elevated admission blood pressure and potential contribution to blood brain barrier disruption. To study whether differences in immune response between patients in both groups existed past admission, we also analyzed differential gene expression for these groups at 5 hours and 24 hours after stroke onset.

    Methods: Blood samples from acute ischemic stroke patients were collected within 3 hours (prior to treatment with thrombolytic), 5 hours and 24 hours of stroke onset. Patients were grouped by admission BP above 185/110 mm Hg (n=19) and BP below 185/110 mm Hg (n=47). Total blood RNA was assessed by whole genome microarray and differential gene expression for admission, 5 hour and 24-hour time points was analyzed by ANCOVA. Functional analysis of identified genes was performed. Correlation analysis was conducted to identify genes associated with systolic blood pressure (SBP).

    Results: Strokes with admission BP above 185/110 mm Hg had 226 genes differentially expressed at admission (within 3 hours of stroke onset) as compared to strokes with BP below 185/110 mm Hg (p < 0.05, fold change ≥ |1.2|). In the higher BP group, SBP remained significantly elevated at 5-hours (p < 0.05) and non-significantly elevated at 24 hours, whereas in the lower BP group, SBP stabilized at 5 hours. Therefore, we also evaluated differential gene expression between the higher and lower BP group at 5 hours and 24 hours post-stroke. At 5 hours, 923 genes were differentially expressed between the higher and lower BP groups and at 24 hours, 422 genes were differentially expressed by admission blood pressure (p < 0.05, fold change ≥ |1.2|). Key genes associated with BP above 185/110 mm Hg included EDN3 (Endothelin-3), MMP21 (Matrix metallopeptidase 21), MMP-25 (matrix metallopeptidase 25), MMP-28 (matrix metallopeptidase 28), TLR4 (toll-like receptor 4), AREG (amphiregulin), CAV-1 (caveolin 1) and CCR2 (Chemokine receptor 2). Key pathways were associated with adaptive immunity, IL-17 and TH17 signalling, TLR signalling and nitric oxide signalling. 99 genes linearly correlated with systolic blood pressure including CCR2 (r = -0.32, P = 0.0009), and AREG (r = 0.286, P = 0.024,) (r > |0.2|, p < 0.05).

    Conclusions: A blood pressure greater than 185/110 mm Hg is associated with differential immune activation in patients with acute ischemic stroke which persists for at least the first 24 hours after stroke. These differences may contribute to blood brain barrier disruption and risk of HT in acute stroke patients with very high admission blood pressure. Whether modulating immune activation could reduce blood brain barrier disruption and risk of HT requires further study.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.