[Show abstract][Hide abstract] ABSTRACT: The ventral anterior nucleus of the thalamus (VATh) gathers motor information from the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNpr) of the basal ganglia and projects directly to motor areas of cortex. GPi/SNpr send their tonically active gamma-aminobutyric acid (GABA)ergic outputs to VATh. The abnormal firing patterns of GABAergic neurons in GPi/SNpr lead to motor deficits. In Parkinson's disease, the spontaneous firing pattern of GPi/SNpr neurons is abnormal due to the degeneration of the nigrostriatal dopaminergic pathway. In a previous study, we found that systemically administered vasoactive intestinal peptide (VIP) was effective at reversing the motor deficits (but not the decline in striatal dopamine levels) in a rat model of Parkinson's disease (6-hydroxydopamine (6-OHDA) exposure). In addition to the beneficial effects on the motor response, VIP could also attenuate both neuronal cell death and the characteristic loss of the myelin sheath that is associated with 6-OHDA administration into the rat striatum. VIP was thought to preserve neurons by inducing native brain mast cells to adopt a nondegranulating phenotype that had the ability to secrete numerous neuroprotective substances, such as nerve growth factor (NGF) and heparin. In the present study, the effect of systemically administered VIP (25 ng/kg i.p.) was investigated on GABA levels of the VATh, dopamine/3,4-dihydroxyphenylacetic acid (DOPAC) levels in the corpus striatum, and the NGF, rat mast cell protease II (RMCPII), serotonin, and heparin content of brain mast cells in 6-OHDA-lesioned rats. Extracellular concentrations of GABA, dopamine, and DOPAC were measured by microdialysis and high-performance liquid chromatography. NGF, RMCPII, serotonin, and heparin levels were examined by immunohistochemical staining techniques. A total of 48 young adult Sprague-Dawley rats were used in the study, and these were assigned to one of six groups. Unilateral injection of 6-OHDA, 2 microl (6 mg/microl), was made into the right corpus striatum. VIP-treated animals received 25 ng/kg VIP i.p. at 2-day intervals for a period of 15 days. The present results demonstrated that VIP significantly increased the levels of GABA in the VATh that were reduced by 6-OHDA application and increased the number of NGF-immunoreactive mast cells but did not alter dopamine metabolism. Therefore, the protective effect of VIP on motor function is possibly related to the increased levels of GABA in the VATh, and its neuroprotective actions may be mediated by the release of NGF from brain mast cells.
Journal of Molecular Neuroscience 12/2009; 41(2):278-87. · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We postulated that a multi-potential agent such as dexanabinol may prevent the development of vasospasm after subarachnoid hemorrhage. We tested the effect of dexanabinol (10 mg/kg) on established vasospasm in a rat femoral artery model. Dexanabinol was given as single or repeated doses. On the 7th day after blood application, vessels were prepared for transmission electron microscopy studies, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining, and studying vessel morphology including luminal area and wall thickness. Application of blood to femoral artery caused a significant narrowing of luminal area (p<0.001) and a marked increase of radial wall thickness (p<0.001) when compared to controls. Similar to its single injection, repeated doses of dexanabinol markedly widened luminal area (p<0.001) near to control values (p>0.05) and decreased radial wall thickness significantly compared to hemorrhage (p<0.05) and vehicle-treated groups (for single p<0.05 and repetitive injections p<0.01). Both single and multiple dexanabinol injections also lowered apoptotic index (p<0.001). In conclusion, dexanabinol seems to prevent established vasospasm and endothelial cell apoptosis.
[Show abstract][Hide abstract] ABSTRACT: In the present study, the effect of systemically administered vasoactive intestinal peptide (VIP) (25 ng/kg i.p.) was investigated on drug-induced rotational behavior, extra-cellular dopamine levels and histology of corpus striatum in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. After 15 days of 6-OHDA lesion, apomorphine-induced (0.05 mg/kg s.c.) rotational behavior of the animals significantly increased and extra-cellular dopamine levels of corpus striatum were significantly reduced. VIP reversed the rotational deficits but did not alter the decrease in striatal dopamine levels. On the other hand, histological data indicate that VIP significantly reduced neuronal death and demyelination. Electron microscopic appearance of mast cells showed ultra-structural variety between VIP-treated and 6-OHDA lesioned groups. VIP activates mast cells without any evidence of typical exocytosis, and possibly mast cells could participate in neuroprotection. Our results suggest that systemically administered VIP can attenuate the motor response changes, neuronal cell death, and myelin sheet loss characteristically associated with 12 microg 6-OHDA administration into the rat striatum. Brain mast cells seem to participate in neuronal protection. Possibly, protective cues could be produced by brain mast cells.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of bombesin on disseminated candidiasis, and compared the effectiveness of bombesin with Saccharomyces boulardii against Candida albicans translocation from the gastrointestinal tract in immunosuppressed rats.
Sixty rats were divided into five groups of 12. Group 1 was given only a laboratory pellet diet and water during the experiments; the other four groups were orally inoculated with C. albicans; and groups 3, 4, and 5 were also given prednisolone intraperitoneally. The treatment groups consisted of group 4, given S. boulardii orally, and group 5, given bombesin subcutaneously. The rats were killed after 10 days, and the large bowel, liver, spleen, and kidneys were removed for microbiological and histopathological examination. Blood samples were taken to measure tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) levels, and the results were compared.
The number of translocated C. albicans colonies from the gastrointestinal tract and the serum TNF-alpha and IL-beta levels were significantly lower in groups 4 and 5 than in group 3 (P < 0.05). Histological analysis revealed that the bombesin-treated group (group 5) had significantly less mucosal ulceration and submucosal inflammation in the large bowel, less inflammation and necrosis in the liver, and less inflammation of the Bowman capsules in the kidney than the S. boulardii-treated group (group 4) (P < 0.05).
These findings show that both S. boulardii and bombesin inhibit the translocation of C. albicans from the gastrointestinal tract, although mucosal ulceration, submucosal inflammation in the large bowel, and dissemination in the liver and kidneys were significantly less severe in the bombesin-treated immunosuppressed rats.
Surgery Today 01/2005; 35(10):869-73. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of cold-restraint stress, repeated over 3 days, and treatment of rats with vasoactive intestinal peptide (VIP) on the contractile responses of isolated aorta to vasoconstrictors, and on aortic adventitial mast cells were investigated. Stress significantly reduced the contractile response of rat aorta smooth muscle to norepinephrine (NE), angiotensin II (Ang II) and vasopressin (VP). Decreased sensitivity to NE, Ang II and VP may result from decreased receptor density, and affinity or reduced effector efficacy. Stress induced degranulation, decreased the number and changed the granular content of mast cells; all degranulated mast cells were stained with alcian blue, and the percentage of safranin staining cells was decreased. Given prior to stress, VIP reversed the reduced contractile responses and sensitivity of aorta to NE and Ang II but had no effect on VP subsensitivity. VIP also inhibited stress-induced degranulation of mast cells, and after VIP only alcian blue-stained mast cells were seen. When VIP was given to non-stressed rats, the contractile response of the aorta to NE, but not Ang II or VP, was increased compared with control. Mast cell count was decreased in the adventitia of non-stressed VIP treated rats. The results indicate that stress decreases the heparin content of mast cells and VIP has an additive effect. In conclusion, VIP modulates both stress-induced mast cell activity and reduced sensitivity of aorta smooth muscle to NE and Ang II. It can be suggested that VIP may moderate some effects of stress on vascular pathophysiology.
[Show abstract][Hide abstract] ABSTRACT: Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock.
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of cold-restraint stress ulcer involves various factors and is not completely understood. Mast cell degranulation, increased gastric muscular contractility, diminished mucosal blood flow, release of several biogenic amines, activated polymorphonuclear leukocytes, and lipid peroxidation which results from toxic oxygen molecules were suggested to be related to the production of gastric damage by cold-restraint stress. Recent evidence strongly indicates that VIP has a modulatory effect on tissue injury. Sprague-Dawley rats were used in two series of experiments. One set of rats was exposed to cold-restraint stress with some of the rats pretreated with VIP. The second set of rats was exposed to cold-restraint stress and then was administered VIP for different durations. Cold-restraint stress induced gastric lesions and mast cell degranulation and also increased lipid peroxidation in gastric tissue. VIP prevented stress-induced ulcers and mast cell degranulation and protected gastric tissue from lipid peroxidation. When VIP was used after induction of stress ulcer it was therapeutically beneficial. Thanks to its antioxidant and anti-inflammatory activity, VIP can be valuable in the prevention of gastric mucosal damage induced by cold-restraint stress.
Annals of the New York Academy of Sciences 01/1999; 865:309-22. · 4.38 Impact Factor