Reperfusion Therapy for Acute Stroke Improves Outcome by Decreasing Neuroinflammation

Abstract

Inflammation is a major step in the ischemic cascade, and proinflammatory cytokines, adhesion molecules and chemokines have been related to brain injury after stroke. To investigate if tissue plasminogen activator (tPA) treatment decreases the deleterious neuroinflammatory response that follows ischemic stroke. Our target population was 80 patients with ischemic stroke involving the middle cerebral artery (MCA) territory. Among them, 41 received tPA within 3 h of symptom onset according to National Institute of Neurological Disorders and Stroke recommendations and the remaining 39 were assessed prior to local approval of tPA. In all patients, blood samples were obtained at 12 and 24 h after symptom onset. Serum determinations of interleukin (IL)-6, inter-cellular adhesion molecule 1 (ICAM-1), IL-8 and tumor necrosis factor-alpha (TNF-α) were obtained by ELISA. National Institutes of Health Stroke Scale (NIHSS) and transcranial Doppler recordings (proximal/distal occlusion, p.o/d.o) were obtained at baseline and follow-up. No differences were found between the two groups in baseline NIHSS scores (tPA = 17 and control = 17; p = 0.38) or MCA status (tPA: p.o = 65.8%, control: p.o = 55.3%; p = 0.41). We found a lower level of mean IL-6 and IL-8 in the tPA treatment group: IL-6 (14.06 vs. 37.88 pg/ml, p = 0.001) and IL-8 (70.98 vs. 465 pg/ml, p < 0.001). No significant changes appeared for ICAM-1 and TNF-α. This biological response was accompanied by a neurological improvement (24 h NIHSS: tPA = 11 and control = 15; p = 0.024) and a mortality reduction (tPA = 9.75% vs. controls = 28.2%; p = 0.038). Patients who improved and those who recanalised had the lowest IL-6 levels (p < 0.005). tPA treatment reduces the severity of the inflammatory phenomena that follows stroke. These results may partially explain the efficacy of reperfusion therapy on stroke outcome.