Apremilast exerts protective effects on stroke outcomes and blood–brain barrier (BBB) dysfunction through regulating Rho‐associated protein kinase 2 expression

Abstract

Aims: Stroke is a devastating event and a huge public health concern worldwide.Apremilast (APR) is a selective inhibitor of phosphodiesterase-4 involved in various neurological diseases, including stroke. However, the protective effects of APR on stroke have not been investigated. Here, we explored the effects of APR on stroke outcomes and blood-brain barrier (BBB) dysfunction using a middle cerebral artery occlusion (MCAO) stroke mice model. Results:The results show that APR attenuated neurological injury in MCAO mice with decreased neurological deficit scores and infarct size, as well as increased hanging grip time. The increased BBB permeability and decreased expression of the tight junction protein Claudin-5 in MCAO mice were attenuated by APR treatment. APR treatment also mitigated neuroinflammation in MCAO mice, as shown by the decreased levels of inflammatory cytokines. In vitro assays also proved that APR ameliorated the oxygen/glucose deprivation/reoxygenation (OGD/R)-induced increase in endothelial permeability and restored the expression of Claudin-5 in bEnd.3 brain endothelial cells.Moreover, overexpression of ROCK2 in bEnd.3 cells abolished the protective effects of APR on endothelial permeability against OGD/R induction. Conclusion:Taken together, our results demonstrate that APR showed significant efficacy on ischemic stroke outcomes by alleviating enhanced BBB permeability and neuroinflammation by inhibiting ROCK2. These findings suggest a novel therapeutic window for ischemic stroke.

Ischemic cerebral stroke risk under psoriasis and psoriatic arthritis treatment: A real‐world observational study from the French national healthcare system database

“…Interestingly, apremilast has been recently suggested to have protective effect on cerebral ischemic stroke in a mouse model. 7 Taking together, our data suggest an increased risk of ICS in psoriasis population treated with anti-IL23 antibodies compared to general population, unlike other treatments. However, no specific increased risk is observed with risankizumab as compared to the other anti-IL-23 antibodies.…”

Effects on Lipid Profile after One Year of Apremilast Therapy in Patients with Psoriasis: A Monocentric Experience

“…Arias de la Rosa et al also observed that treatment with apremilast significantly reduced the levels of CVD-related markers (in particular of CVD-related proteins associated with the pathogenesis of PsA, including FABP-4, GAL-3, MMP3, and CD163), particularly in patients with a higher prevalence of cardiometabolic comorbidities [ 13 ]. Moreover, a recent study on stroke in mice models found a significant efficacy of apremilast on ischemic stroke outcomes by alleviating enhanced blood–brain barrier permeability and neuroinflammation through ROCK2 inhibition, suggesting its potential use as a therapeutic option for ischemic stroke [ 26 ].…”