Background and Aims: to evaluate the effect of circulating inflammatory mediators, matrix metalloproteinases (MMP), MMP inhibitors and inducers on blood-brain-barrier (BBB) leakage in the acute phase of stroke.
Methods: observational prospective single-centre hospital-based study that included ischaemic stroke patients treated with revascularization treatments. Circulating biomarkers were taken before and after 24 hours from acute interventions. We assessed pre-treatment BBB leakage with CT perfusion by using Ktrans within the ischaemic area (Fig 1). We evaluated independent associations between BBB leakage and biomarkers quartile levels at baseline, 24 hours and their relative variations [(∆=24hours level- baseline level)/baseline level] adjusting for age, sex, baseline stroke severity and onset to treatment time (for protocol details see Piccardi et al. BMJ Open 2018).Results: we included 79 patients, mean (±SD) age was 75.9 (±11.6), 41 (52%) males, median (IQR) NIHSS was 17 (11- 23). Endovascular treatment alone was performed in 38 (48%) patients, intravenous thrombolysis in 21 (27%) patients, and 20 patients (25%) received both treatments.
We did not find any association between baseline biomarker values and BBB leakage.BBB leakage was correlated with 24h extracellular matrix metalloproteinase inducer (EMMPRIM) levels (ρ= 0.25, p=0.02), 24h IL-12 (ρ= 0.27, p=0,014), and with ∆EMMPRIM levels (ρ= 0.23; p=0.048) (Fig 2). In ordinal analysis, BBB leakage was not associated with 24h EMMPRIM levels OR=3.18 (CI 0.97- 10.39), but remained associated with ∆EMMPRIM levels (OR=6.21; 95%CI=1.53-25.3) and IL-12 levels (OR=3.69; 95%CI=1.16-11.7).Conclusions: early BBB leakage was associated with 24 hours variation in EMMPRIM and IL12 levels. Our results support a possible link between BBB disruption and consequent inflammatory cascade in acute ischemic stroke

CIRCULATING BIOMARKERS AND BLOOD-BRAIN-BARRIER LEAKAGE: RESULTS FROM THE REPERFUSION INJURY IN ISCHEMIC STROKE (RISK) STUDY