AUTHOR=Sun Xiaohui , Wang Tian , Zhou Lin , Zhang Ce , Fu Fenghua 

TITLE=The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1073099

DOI=10.3389/fphar.2023.1073099

ISSN=1663-9812

ABSTRACT=<p><bold>Purpose:</bold> The aim is to investigate the effect of toludesvenlafaxine (Tdv), a reuptake inhibitor of serotonin, norepinephrine, and dopamine, on the neurological function in cerebral ischemic rats and the underlying mechanisms.</p><p><bold>Material and Methods:</bold> Middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced in rats and the neuroprotective effects of Tdv were evaluated by infarct size, Garcia test, and beam walking test. Neuronal apoptosis in the peri-infarct area was observed by TUNEL staining. And the apoptosis-related proteins were evaluated with Western blotting. The role of CREB pathway in effect of Tdv was also investigated using Western blotting and immunofluorescence.</p><p><bold>Results:</bold> In the MCAO/R model, administration of Tdv reduced the infarct size, promoted neural functional recovery, decreased the expression of Bax and Caspase-3, and increased the expression of Bcl-2 and BDNF. In addition, Tdv reduced neuronal apoptosis in the peri-infarct area. Tdv increased the expression of phosphorylated CREB. The application of the specific CREB inhibitor, compound 666-15, could reverse the anti-ischemic cerebral injury of Tdv in MCAO/R rats.</p><p><bold>Conclusion:</bold> Tdv ameliorated cerebral ischemic injury through reducing neuronal apoptosis and increasing the expression of BDNF via the activation of CREB pathway.</p>