Endogenous Pituitary Adenylate Cyclase Activating Polypeptide Is Involved in Suppression of Edema in the Ischemic Brain

Nakamachi, Tomoya; Ohtaki, Hirokazu; Yofu, Sachiko; Dohi, Kenji; Watanabe, Jun; Mori, Hiromu; Satō, Atsushi; Hashimoto, Hitoshi; Shintani, Norihito; Baba, Akemichi; Shioda, Seiji

doi:10.1007/978-3-211-98811-4_6

Cited by 39 publications

(29 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the neuroprotection, in the present study we also observed that PACAP decreased the significant edema formation in the retina 7 days after irradiation. The mechanism for this is not known, but recently, a similar observation has been made in ischemic brain edema formation (Nakamachi et al 2010). Figure 1 Morphology of representative retinas from control (a) and different treated animals: exposed to diffuse UV-A radiation (b, c, g) and combined with intravitreal PACAP treatment (d, e, f).…”

Section: Discussionmentioning

confidence: 74%

Effects of PACAP in UV-A Radiation-Induced Retinal Degeneration Models in Rats

et al. 2010

View full text Add to dashboard Cite

The retina is constantly exposed to ultraviolet (UV) light with different wavelengths, which may lead to chronic UV-induced retinal injury. In our previous studies, we have shown the protective effects of pituitary adenylate cyclase activating polypeptide (PACAP) in toxic and ischemic retinal injuries. The aim of the present study was to investigate the effects of PACAP in UV-A-induced retinal lesion. We used diffuse UV-A radiation (315-400 nm) to induce acute retinal damage over a short period of exposure. Using standard histological (morphological and morphometrical) analysis, we assessed the actions of intravitreal PACAP (100 pmol/5 µl) treatment on acute UV-A-induced retinal damage. We measured the thickness of nuclear and plexiform layers as well as the number of cells in the outer nuclear and inner nuclear layers and in the ganglion cell layer. Outer limiting membrane-inner limiting membrane distances in the cross-section of the retina were also examined. Our results show that UV-A light-induced retinal damage led to severe degeneration in the photoreceptor layer, and in the outer and inner nuclear layers. Alteration in the plexiform layers was also observed. We found that post-irradiation PACAP treatment significantly attenuated the UV-A-induced retinal damage. Our results provide the basis for future clinical application of PACAP treatment in retinal degeneration and may have clinical implications in several ophthalmic diseases.

show abstract

Section: Discussionmentioning

confidence: 74%

Effects of PACAP in UV-A Radiation-Induced Retinal Degeneration Models in Rats

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In vivo, PACAP deficient mice are more vulnerable to experimental autoimmune encephalomyelitis (Tan et al 2009) and display slower recovery after peripheral nerve crush injury (Armstrong et al 2008). It has also been shown that these mice develop larger infarct volume and increased edema in focal cerebral ischemia (Chen et al 2006;Nakamachi et al 2010;Ohtaki et al 2006). This endogenous protective effect of PACAP in ischemic lesions seems to be not restricted to the brain, but similar findings have been described in peripheral tissues.…”

Section: Discussionmentioning

confidence: 96%

Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo

et al. 2011

View full text Add to dashboard Cite

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective peptide exerting protective effects in neuronal injuries. We have provided evidence that PACAP is neuroprotective in several models of retinal degeneration in vivo. Our previous studies showed that PACAP treatment ameliorated the damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid artery occlusion. We have also demonstrated in earlier studies that treatment with PACAP antagonists further aggravates retinal lesions. It has been shown that PACAP deficient mice have larger infarct size in cerebral ischemia. The aim of this study was to compare the degree of retinal damage in wild type and PACAP deficient mice in ischemic retinal insult. Mice underwent 10 min of bilateral carotid artery occlusion followed by 2-week reperfusion period. Retinas were then processed for histological analysis. It was found that PACAP deficient mice had significantly greater retinal damage, as shown by the thickness of the whole retina, the morphometric analysis of the individual retinal layers, and the cell numbers in the inner nuclear and ganglion cell layers. Exogenous PACAP administration could partially protect against retinal degeneration in PACAP deficient mice. These results clearly show that endogenous PACAP reacts as a stress-response peptide that is necessary for endogenous protection against different retinal insults.

show abstract

“…This is also true for ischemic injuries. Ohtaki and coworkers showed that PACAP KO mice have increased infarct volume in a model of stroke [ 60 ] with increased edema formation [ 61 ]. Similar results were obtained in the retina: in bilateral carotid artery occlusioninduced retinal ischemia PACAP KO mice showed increased tissue damage [ 62 ].…”

Section: Small Intestinal Ischemic Injury In Pacap Knockout (Ko) Micementioning

confidence: 63%

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Horváth

Illés

Heimesaat

et al. 2016

Current Topics in Neurotoxicity

View full text Add to dashboard Cite

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia-reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine.

show abstract

Endogenous Pituitary Adenylate Cyclase Activating Polypeptide Is Involved in Suppression of Edema in the Ischemic Brain

Cited by 39 publications

References 16 publications

Effects of PACAP in UV-A Radiation-Induced Retinal Degeneration Models in Rats

Effects of PACAP in UV-A Radiation-Induced Retinal Degeneration Models in Rats

Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Contact Info

Product

Resources

About