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Pericytes, important elements of the blood-brain barrier (BBB), play critical roles in maintaining BBB integrity and modulating hemostasis, angiogenesis, inflammation and phagocytic function. We investigated whether pericytes are involved in the recombinant tissue plasminogen activator (rt-PA)-induced inflammatory response, which disrupts the BBB, and investigated the potential mechanisms. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) were employed to mimic hypoxic-ischemic conditions. Rt-PA was intravenously injected into mice 1 h after 1 h MCAO, and Rt-PA was added to the culture medium after 4 h OGD. Rt-PA treatment aggravated the disruption of the BBB compared with hypoxia treatment, and etanercept (TNF-α inhibitor) combined with rt-PA alleviated the rt-PA-induced BBB disruption in vivo and in vitro. Rt-PA treatment increased the TNF-α and MCP-1 levels and decreased the TGF-β, p-Smad2/3 and PDGFR-β levels compared with hypoxia treatment in vivo and vitro. TGF-β combined with rt-PA decreased TNF-α and MCP-1 secretion and alleviated BBB disruption compared with rt-PA; these changes were abrogated by TPO427736 HCL (a TGF-β/p-Smad2/3 pathway inhibitor) cotreatment in vitro. Rt-PA did not decrease TGF-β and p-Smad2/3 expression in PDGFR-β-overexpressing pericytes after OGD. These findings identify PDGFR-β/TGF-β/p-Smad2/3 signaling in pericytes as a new therapeutic target for the treatment of rt-PA-induced BBB damage.

BackgroundEarly rehabilitation (ER) has been reported to be both safe and feasible for patients' post-stroke. To date, however, ER-related outcomes concerning patients who have undergone mechanical thrombectomy (MT) have not been investigated. This study aimed to determine the feasibility of ER and whether it improves prognosis in such patients.MethodsIn this single-center, double-blinded, randomized controlled study involving 103 patients who met the study criteria (i.e., has undergone MT), we randomly divided patients (1:1) into ER and conventional rehabilitation groups. The primary outcome was mortality, while secondary outcomes included favorable outcomes (modified Rankin scale of 0–2), the incidence of non-fatal complications, and Barthel Index (BI) scores. We assessed outcomes at 3 months and 1-year post-stroke.ResultsNo significant between-group differences were found in terms of mortality and favorable outcomes at 3 months and 1-year post-stroke. At 3 months, 15 (28.8%) patients in the ER group and 29 (56.9%) in the conventional rehabilitation group (p = 0.002) had non-fatal complications. The BI in the ER and conventional rehabilitation groups was 100 (85–100) and 87.5 (60–100), respectively, (p = 0.007). At 1 year, the incidence of non-fatal complications was similar between both groups [BI in the ER group, 100 (90–100), p = 0.235; BI in the conventional rehabilitation group, 90 (63.8–100); p = 0.003].ConclusionEarly rehabilitation (ER) reduces the incidence of early immobility-related complications and effectively improves patients' activities of daily living on a short- and long-term basis. Our results indicate that MT contributes to ER in patients with stroke.Clinical Trial Registrationwww.chictr.org.cn, identifier: ChiCTR1900022665.