Novel Neuroprotective Strategies in Ischemic Retinal Lesions

Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K+ channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques

Neuroprotective effects of PACAP in the retina

Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide that is well-known for its general cytoprotective effects in different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors also occur in the retina. In this review, we summarize the retinoprotective effects of PACAP. In vitro, PACAP is protective against glutamate, thapsigargin, anisomycin, oxidative stress, UV light, high glucose, inflammation and anoxia. Both the neural retina and the pigment epithelial cells can be protected by PACAP in various experimental paradigms. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models in rats and mice: excitotoxic injury induced by glutamate, N-methyl-D-aspartate (NMDA) or kainate, ischemic injury induced by carotid artery ligation and high intraocular pressure, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy as well as retinopathy of prematurity. Molecular biological methods have revealed that PACAP activates anti-apoptotic, while inhibits pro-apoptotic signaling pathways, and it also stimulates an anti-inflammatory environment in the retina. Altogether, PACAP is suggested to be a potential therapeutic retinoprotective agent in various retinal diseases

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

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

Investigation of PACAP Fragments and Related Peptides in Chronic Retinal Hypoperfusion

Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective effects in different neuronal and retinal injuries. Retinal ischemia can be effectively modelled by permanent bilateral common carotid artery occlusion (BCCAO), which causes chronic hypoperfusion-induced degeneration in the entire rat retina. The retinoprotective effect of PACAP 1-38 and VIP is well-established in ischemic retinopathy. However, little is known about the effects of related peptides and PACAP fragments in ischemic retinopathy. The aim of the present study was to investigate the potential retinoprotective effects of different PACAP fragments (PACAP 4-13, 4-22, 6-10, 6-15, 11-15, and 20-31) and related peptides (secretin, glucagon) in BCCAO-induced ischemic retinopathy. Wistar rats (3-4 months old) were used in the experiment. After performing BCCAO, the right eyes of the animals were treated with PACAP fragments or related peptides intravitreal (100 pM), while the left eyes were injected with saline serving as control eyes. Sham-operated (without BCCAO) rats received the same treatment. Routine histology was performed 2 weeks after the surgery; cells were counted and the thickness of retinal layers was compared. Our results revealed significant neuroprotection by PACAP 1-38 but did not reveal retinoprotective effect of the PACAP fragments or related peptides. These results suggest that PACAP 1-38 has the greatest efficacy in ischemic retinopathy

Association between Obesity and Overweight and Cardiorespiratory and Muscle Performance in Adolescents

The high prevalence of obesity in childhood and adolescence has major public health consequences, since it is associated with various chronic diseases in the short- and long-term. The goal of our study was to examine the possible association between obesity and overweight and cardiorespiratory and muscle performance during a 4-year follow up period in adolescents. The body mass index (BMI) and physical performance of adolescents (360 girls and 348 boys) between 14–18 years of age was measured twice a year, and the possible correlation between overweight and obesity and cardiorespiratory and muscle performances were investigated. Our results revealed that cardiorespiratory performance increased significantly in boys during the 4 years (p < 0.001), but the aerobic performance of girls only showed seasonal fluctuation. Muscle performance significantly increased both in boys and girls (p < 0.001). Inverse association between obesity and cardiorespiratory and muscle performance was proved. Overweight was also inversely correlated with cardiorespiratory performance, but it demonstrated no correlation with muscle strength. Avoiding increased BMI and decreased physical fitness is essential for adolescents’ health to prevent short- and long-term adverse effects

Effects of maternal stress during different periods of pregnancy on the early neurobehavioral response of rats

Background: Several studies focus on the effects of prenatal stress in adulthood. Relatively little is known about the early neurodevelopmental consequences of such experiences and their predictive value. Thus we examined the early neurobehavioral responses of offspring whose mothers were exposed to restraint stress. Methods and results: Pregnant rats were exposed to 60 minutes restraint stress twice a day for seven days in different periods of pregnancy (early/mid and late phase). After birth, offspring were examined for the maturation of neural signs and reflexes daily for 3 weeks. Mid-pregnancy stress resulted in a subtle faster development in the appearance of eyelid and auditory startle reflexes, and in the disappearance of crossed extensor reflex. Pups exposed to stress in the last week of intrauterine life displayed a delay in air righting and showed a slight enhancement in the appearance of auditory startle. Conclusion: Based on our present findings, the deleterious consequences of prenatal stress are not apparent during the early developmental stages at least not detectable with the battery of test most widely used to examine neurobehavioral development. However, these findings draw the attention of the need of careful awareness in later ages in spite of the normal neurobehavioral development of newborns exposed to prenatal stress.Fil: Kvarik, Timea. University of Pécs; HungríaFil: Mammel, Barbara. University of Pécs; HungríaFil: Reglodi, Dora. University of Pécs; HungríaFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Farkas, Jozsef. University of Pécs; HungríaFil: Tamas, Andrea. University of Pécs; HungríaFil: Ertl, Tibor. University of Pécs; HungríaFil: Atlasz, Tamas. University of Pécs; HungríaFil: Bodzai, Greta. University of Pécs; HungríaFil: Kiss, Peter. University of Pécs; HungríaFil: Gyarmati, Judit. University of Pécs; Hungrí

Protective effects of pituitary adenylate cyclase activating polypeptide against neurotoxic agents

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide highly expressed in the central and peripheral nervous system, where it exerts several neuromodulatory functions and is an important trophic and protective factor. PACAP has been shown to activate several protective pathways, mainly through its specific PAC1 receptor and protein kinase A, C and MAP kinases downstream. It has been shown to have very potent neuroprotective actions against different neurotoxic agents both in vitro and in vivo. The aim of the present review is to provide an overview on the neurotoxic injuries against which PACAP exerts protection, and to give an insight into its protective mechanism. We give a summary of the neuroprotective effects against the most commonly used neurotoxic agents, such as 6-OHDA, MPTP, glutamate and some less well-known neurotoxic compounds. Also endogenous PACAP has neuroprotective effects, known from studies in PACAP knockout mice or from blocking endogenous effects by antagonists. Altogether, the vast amount of data for the neuroprotective effects of PACAP give a firm background for its endogenous role as part of the neuroprotective machinery and its possible future therapeutic use as a neuroprotective factor

PACAP deficiency as a model of aging

L