Role of PACAP in Ischemic Neural Death

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that was first isolated from an ovine hypothalamus in 1989. Since its discovery, more than 2,000 papers have reported on the tissue and cellular distribution and functional significance of PACAP. A number of papers have reported that PACAP but not the vasoactive intestinal peptide suppressed neuronal cell death or decreased infarct volume after global and focal ischemia in rodents, even if PACAP was administered several hours after ischemia induction. In addition, recent studies using PACAP gene-deficient mice demonstrated that endogenous PACAP also contributes greatly to neuroprotection similarly to exogenously administered PACAP. The studies suggest that neuroprotection by PACAP might extend the therapeutic time window for treatment of ischemia-related conditions, such as stroke. This review summarizes the effects of PACAP on ischemic neuronal cell death, and the mechanism clarified in vivo ischemic studies. In addition, the prospective mechanism of PACAP on ischemic neuroprotection from in vitro neuronal and neuronal-like cell cultures with injured stress model is reviewed. Finally, the development of PACAP and/or receptor agonists for human therapy is discussed.

Delayed Pituitary Adenylate Cyclase–Activating Polypeptide Delivery After Brain Stroke Improves Functional Recovery by Inducing M2 Microglia/Macrophage Polarization

“…11,19 Nevertheless, there are several hurdles that need to be addressed before these approaches can be used in therapy. To circumvent these limitations, we integrated the 2 approaches by establishing a stem cell line designed to produce and release PACAP ( Figure I in the online-only Data Supplement).…”

Effects of PACAP on Mitochondrial Apoptotic Pathways and Cytokine Expression in Rats Subjected to Renal Ischemia/Reperfusion

“…Also, the present study is in accordance with other studies demonstrating the protective effects of PACAP in ischemic injury of other tissues, such as in vivo global and focal cerebral ischemia, retinal ischemia. and in vitro ischemia/reperfusion injury of cardiomyocytes (Atlasz et al 2010;Banks et al 1996;Ohtaki et al 2008;Racz et al 2008;Tamas et al 2002).…”

“…PACAP has been shown to have protective effects against ischemia-induced tissue damage in the nervous system and also in the periphery, such as in the small intestine (Ferencz et al 2009;Ohtaki et al 2008). Ischemia/ reperfusion injury is characterized by common mechanisms in all tissues.…”

Regulation of Oxidative Stress by Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Mediated by PACAP Receptor

“…The receptors are widely distributed in the body (Vaudry et al 2000) and play diverse roles not only in the central nervous system but also in other organs and tissues. Numerous in vivo and in vitro studies have suggested that PACAP is involved in the suppression of neural (Uchida et al 1996;Reglodi et al 2000;Ohtaki et al 2006Ohtaki et al , 2008Ravni et al 2006) and other forms of cellular death (Arimura et al 2005;Gasz et al 2006;Racz et al 2007;Mori et al 2010), the modulation or suppression of immune and inflammatory responses (Delgado and Ganea 2001;Abad et al 2002;Martinez et al 2002;Ganea and Delgado 2002), and the dilation of vessels and bronchi (Linden 1999;Groneberg et al 2006;Ohtaki et al 2004), as well as playing a role in psychomotor control (Hashimoto et al 2001(Hashimoto et al , 2006.…”