Effect of blood pressure on early neurological deterioration of acute ischemic stroke patients with intravenous rt-PA thrombolysis may be mediated through oxidative stress induced blood-brain barrier disruption and AQP4 upregulation

J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104997. doi: 10.1016/j.jstrokecerebrovasdis.2020.104997. Epub 2020 Jun 13.

Abstract

Objective: To study association between blood pressure (BP) and development of early neurological deterioration (END) in acute ischemic stroke patients with intravenous rt-PA thrombolysis and its possible mechanism.

Methods: We prospectively collected data of acute ischemic stroke patients with intravenous rt-PA thrombolysis from March 2015 to June 2019. The collected data include general, clinical data and laboratory test. Moreover, serum levels or activity of malondialdehyde (MDA), superoxide dismutase (SOD), matrix metalloproteinase-9 (MMP-9), occludin(OCLN), ZO-1 and aquaporin 4(AQP-4) were determined.

Results: A total of 357 acute ischemic stroke patients received intravenous rt-PA thrombolysis and 16 cases were eventually excluded. Finally, 341 patients were eligible in this study and 65 patients (19.06%) experienced END. Mean systolic blood pressure (SBP) within 24 h, serum levels or activity of MDA, SOD, MMP-9, ZO-1, OCLN, AQP-4 at 24 h after thrombolysis were the independent predictors for END in the total and hypertension population using multivariate logistic regression analysis, and mean SBP within 24 h was the best predictor for END. Receiver operating characteristic (ROC) analysis found that cutoff mean SBP for END was 148.16 mmHg, and sensitivity was 85.6%. The best target SBP level is 140ཞ149 mmHg. Further, spearman correlation tests indicated that BP levels were directly proportional to serum levels or activity of MDA, MMP-9, ZO-1, OCLN, AQP-4 at 24 h after thrombolysis and neurological deterioration severity.

Conclusions: END frequently occurs after thrombolysis, and the best predictor of END is SBP which may be mediated through oxidative stress induced blood-brain barrier disruption and AQP4 upregulation.

Keywords: AQP4; Blood pressure; Blood-brain barrier; Early neurological deterioration; Intravenous thrombolysis; MMP-9; Oxidative stress.

MeSH terms

  • Aged
  • Aquaporin 4 / blood*
  • Biomarkers / blood
  • Blood Pressure*
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Brain Ischemia / blood
  • Brain Ischemia / diagnosis
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / physiopathology
  • Disease Progression
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Pilot Projects
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Stroke / physiopathology
  • Thrombolytic Therapy / adverse effects*
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / adverse effects*
  • Treatment Outcome
  • Up-Regulation

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Biomarkers
  • Fibrinolytic Agents
  • Tissue Plasminogen Activator