Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male rats

2001 ◽  
Vol 22 (5) ◽  
pp. 213-219 ◽  
Author(s):  
Niels Einer-Jensen ◽  
Lise Larsen ◽  
Stephanie Deprez ◽  
Elaine Starns ◽  
Sheila Schwartz
Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.


1989 ◽  
Vol 257 (3) ◽  
pp. H785-H790
Author(s):  
T. Sakamoto ◽  
W. W. Monafo

[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.


1990 ◽  
Vol 258 (1) ◽  
pp. R70-R76 ◽  
Author(s):  
S. Papas ◽  
P. Smith ◽  
A. V. Ferguson

Extracellular single-unit recordings from neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS) in anesthetized male rats demonstrated that most cells in these regions have spontaneous activities of 5 Hz or less. Systemic angiotensin (ANG II) (50-500 ng) enhanced the activity of 55% of AP cells tested (n = 76), whereas 53% of tested NTS neurons (n = 62) were inhibited by ANG II. To determine whether these neurons were influenced specifically by circulating ANG II or by the accompanying increase in mean arterial blood pressure (BP), the effects of adrenergic agonists given intravenously on ANG II influenced neurons were also examined. Subsequently two cell types were characterized: cells responding to iv ANG II but not to the adrenergic agonist ("ANG II sensitive") and cells responding in a similar way to both agents ("BP sensitive"). Most ANG II-responsive neurons in the AP (53.5%) and the NTS (65%) were determined to be BP sensitive. These data demonstrate that ANG II influences the activity of AP neurons. In addition, there exists a second population of AP neurons apparently responsive to perturbations of the cardiovascular system. These studies further emphasize the potential roles of the AP in the regulation of body fluid balance.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Leon J DeLalio

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.


2021 ◽  
Vol 66 (4) ◽  
pp. 18-24
Author(s):  
I. Ushakov ◽  
Vladimir Fyodorov

Purpose: Comparative assessment of radiation-induced changes in neurons of the cerebral cortex after a single and fractionated exposure to ionizing radiation in doses of 0.1 – 1.0 Gy. Material and methods. The study was carried out in compliance with the rules of bioethics on 180 white outbred male rats at the age of 4 months. by the beginning of the experiment, exposed to a single or fractionated exposure to γ-quanta of 60Co in total doses of 0.1; 0.2; 0.5 and 1.0 Gy. Neuromorphological and histochemical methods were used to assess morphometric and tinctorial parameters of nerve cells, as well as changes in the content of protein and nucleic acids in neurons in the early and late periods of the post-radiation period. Using one-way analysis of variance, a comparative assessment of neuromorphological indicators under various modes of radiation exposure is given. Results: In the control and irradiated animals throughout their life, undulating changes in the indicators of the state of the neurons of the brain occur with a gradual decrease by the end of the experiment. Despite a number of features of the dynamics of neuromorphological parameters, these irradiation regimes do not cause functionally significant changes in the neurons of the cortex. However, in some periods of the post-radiation period, the changes under the studied irradiation regimes were multidirectional and did not always correspond to age control. Significant differences in the response of neurons to these modes of radiation exposure in the sensory and motor areas of the cerebral cortex have not been established. Conclusion: No functionally significant radiation-induced changes in neurons were found either with single or fractionated irradiation. At the same time, different modes of irradiation in general caused the same type of changes in neurons. However, in some periods of observation, changes in neuromorphological parameters under the studied irradiation regimes were not unidirectional and differed from age control, which indicates a possible risk of disturbances in the functioning of the nervous system against the background of other harmful and dangerous factors.


1989 ◽  
Vol 9 (6) ◽  
pp. 886-891 ◽  
Author(s):  
David Barranco ◽  
Leslie N. Sutton ◽  
Sandra Florin ◽  
Joel Greenberg ◽  
Teresa Sinnwell ◽  
...  

19F NMR was used to determine washout curves of an inert, diffusible gas (CHF3) from the cat brain. The cerebral blood flow was estimated from a bi- or tri-phasic fit to the deconvoluted wash-out curve, using the Kety-Schmidt approach. Cerebral blood flow values determined by 19F NMR show the expected responsiveness to alterations in Paco2, but are approximately 28% lower than cerebral blood flow values determined simultaneously by radioactive microsphere techniques. High concentrations of CHF3 have little effect on intracranial pressure, mean arterial blood pressure or Paco2, but cause small changes in the blood flow to certain regions of the brain. We conclude that 19F NMR techniques utilizing low concentrations of CHF3 have potential for the noninvasive measurement of cerebral blood flow.


Author(s):  
Farouk Kamel Elbaz ◽  
Hanan F Aly ◽  
Wagdy Kb Khalil ◽  
Hoda F Booles ◽  
Gamila H Al

ABSTRACTObjective: The present study is aimed to investigate the promising action of Dunaliella salina extract as a natural protector against Alzheimer’sdisease (AD) and reported to possess a variety of activities, including antioxidant effects due to its ability to create large amount of carotenoids.Methods: D. salina is a type of halophile green microalgae was used in the present study. 50 male rats were used in this study, where aluminumchloride was orally administered to induce AD in a dose of 100 mg/kg, daily for 6 weeks. Al-intoxicated rats treated orally daily with D. salinaethanolic extract for 6 weeks in a dose of 150 mg/kg b.wt., whereas standard anti-Alzheimer drug donepezil tartrate was administered at the doseof 10 mg/kg b.wt./day for 6 consecutive weeks. The anti-Alzheimer properties of D. salina extract were achieved through measuring the calmodulin(CaM) level, paraoxonase 1 (PON1) activity, the antiapoptotic marker (Bcl2), brain-derived neurotrophic factor (BDNF), the generation of the DNAadducts (8-hydroxy-2-deoxyguanosine [8-OHdG]/2-deoxy guanosine [2-dG]), and alteration in the expression of amyloid precursor protein, β-siteAPP-cleaving enzyme 1 (BACE1), and β-site APP-cleaving enzyme 2 (BACE2) in AD rats.Results: The current results demonstrated that supplementation of AD rats with D. salina extract-enhanced CaM level, and increased PON1 activity,upregulated Bcl2 and BDNF, decreased the levels of DNA adducts (8-OHdG/2-dG), and suppressed the alterations of the expression levels of APP,BACE1, and BACE2-m RNAs as compared with those in AD rats.Conclusion: It could be concluded that the biological activity of D. salina extract might be regulated by 9-cis b-carotene protecting the brain cells fromthe oxidative stress in AD rats.Keywords: Dunaliella salina, Calmodulin, Paraoxonase 1, Bcl2, Brain-derived neurotrophic factor, Alzheimer’s disease, DNA adduct, Amyloid precursorprotein.


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