Dépôt numérique

PACAP and a novel stable analogue protect rat brain from ischemia through same mechanisms

Dejda, Agnieszka; Seaborn, Tommy; Bourgault, Steve; Touzani, Omar; Fournier, Alain; Vaudry, Hubert et Vaudry, David (2012). PACAP and a novel stable analogue protect rat brain from ischemia through same mechanisms In: 10th International Symposium on VIP-PACAP and Related Peptides, December 13-16, 2011, Eilat, ISRAEL.

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PACAP exerts protective activities in numerous models of neurological disorders involving neurodegeneration. However, the use of PACAP as a clinically efficient drug might be limited due to its poor metabolic stability and adverse physiological effects. By combining identification of enzymatic cleavage sites with targeted chemical modifications, a metabolically stable and potent PACAP38 analogue, acetyl- [Ala15, Ala20]PACAP38-propylamide, was recently developed. The in vivo biological activity of this new compound was evaluated and compared to the native peptide using a rat model of middle cerebral artery occlusion (MCAO). The results show that PACAP38 and its analogue, administered intravenously, strongly reduce the infarct volume and improve neurological impairment induced by stroke. Investigation of the mechanisms involved indicates that the 2 peptides act through same mechanisms. In particular, they inhibit the expression of Bad, caspase 3, MIP-1α, Nos2, TNF-α and NFκB mRNAs, and increase ERK2, Bcl-2 and IL-6 mRNA levels. These results indicate that the neuroprotective effect of PACAP, after MCAO, is not only due to its ability to inhibit apoptosis but also to modulate the inflammatory response. Altogether, the present study highlights the potential therapeutic efficacy of very low concentrations of PACAP or its metabolically stable derivative for the treatment of stroke. This work is supported by INSERM, TC2N Interreg Project, LARC-Neurosciences Network and the Region of Haute-Normandie.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique Journal of Molecular Neuroscience 48(suppl. 1):S8-S159
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 janv. 2024 14:55
Dernière modification: 28 janv. 2024 14:55
URI: https://espace.inrs.ca/id/eprint/14119

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