DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high-glucose conditions, potentially through the SIRT1/HIF-1/VEGF pathway.

BACKGROUND: Vascular disease in diabetes, for example, stroke, presents a significant public health burden. Recently, the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin has been found to counteract stroke among diabetic patients, showing great promise in drug repurposing and indication expansion. However, the molecular basis of this protection mechanism remains unknown. METHODS: The expression and localization of DPP-4 in rat brain microvascular endothelial cells (rBMVECs) were assessed with immunofluorescent staining and Western blotting. The effects of DPP-4 inhibitors on cell proliferation and migration of rBMVECs were determined using MTT and transwell assays, separately. The influence of DPP-4 inhibition on the expression of molecular markers (eg, VEGF, eNOS, HIF-1α. SIRT1) was examined at both mRNA and protein levels with qRT-PCR and Western blotting, individually. RESULTS: DPP-4 inhibitors (40 nmol/L linagliptin, 30 µmol/L berberine) offer protection from hypoxia/high glucose induced impairments in the proliferation and migration of rBMVECs. Treatment with DPP-4 inhibitors counteracted the attenuating effects of hypoxic/high-glucose conditions on the expression of VEGF, eNOS, HIF-1α, and SIRT1, which can be completely eliminated by the inhibition of SIRT1 with 1 mmol/L nicotinamide. CONCLUSIONS: The protection of rBMVECs from hypoxia/high-glucose induced impairment by DPP-4 inhibitors may be mediated by the SIRT1/HIF-1α/VEGF pathway.

A cohort study of isolated brainstem infarction based on head MR imaging and clinical findings.

OBJECTIVE: The prognosis of patients with isolated brainstem infarction (BSI) differs on an individual patient basis. This study was undertaken to analyze the influences of different imaging and clinical features with the prognosis of patients with BSI. METHODS: The study population was derived from a multicenter study of intracranial atherosclerosis in China. In the present study, 300 patients were selected who had experienced non-cardiogenic brain stem infarction within the prior 7 days. Evaluations included clinical characteristics, location and size of the brainstem infarction, and whether the infarction was located in multiple perforating branches of the brainstem. Poor prognosis was defined as the presence of disability within 1 year from the onset of disease. RESULTS: In total, 281 patients were followed up at 1 year post-infarction. Of these 281 patients, 84 (29.9%) exhibited disability at 1 year; these patients showed a median National Institutes of Health Stroke Scale score of 6 on admission. Multiple logistic regression analysis showed that patients with BSI located in the territory of multiple perforating arteries, who were discharged without administration of statins, showed a poor 1-year prognosis. CONCLUSION: Isolated BSI involving multiple perforating arteries, without statin medication at discharge, indicated poor prognosis for patients with BSI.