Blood-Brain Barrier Rescue by Roflumilast After Transient Global Cerebral Ischemia in Rats.

Autor: Bonato JM; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, CEP, 5790, 87020-900, Maringá, Paraná, Brazil., de Mattos BA; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, CEP, 5790, 87020-900, Maringá, Paraná, Brazil., Oliveira DV; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, CEP, 5790, 87020-900, Maringá, Paraná, Brazil., Milani H; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, CEP, 5790, 87020-900, Maringá, Paraná, Brazil., Prickaerts J; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands., de Oliveira RMW; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, CEP, 5790, 87020-900, Maringá, Paraná, Brazil. rmmwoliveira@uem.br.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2023 Aug; Vol. 41 (4), pp. 311-323. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1007/s12640-023-00639-2
Abstrakt: Phosphodiesterase 4 inhibitors (PDE4-I), which selectively increase cyclic adenosine monophosphate (cAMP) levels, have shown neuroprotective effects after several neurological injuries inducing blood-brain barrier (BBB) damage including local/focal cerebral ischemia. The present investigated whether roflumilast confers BBB neuroprotection in the hippocampus after transient global cerebral ischemia (TGCI) in rats. TGCI resulted in whole BBB disruption as measured by the increase of Evans blue (EB) and IgG extravasation, neurodegeneration, and downregulation of claudin-5 and endothelial nitric oxide synthase (eNOS) levels in the CA1 hippocampal subfield of ischemic rats. Roflumilast attenuated BBB disruption and restored the levels of eNOS in the CA1 hippocampal area. Moreover, roflumilast increased the levels of B2 cell lymphoma (BcL-2) and neuron-glial antigen-2 (NG2) in the CA1 subfield after global ischemia in rats. The protective effects of roflumilast against TGCI-induced BBB breakdown might involve preservation of BBB integrity, vascularization and angiogenesis, and myelin repair.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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