scholarly journals Degeneration of pyramidal cells of CA1, CA2, and CA3 area of the hippocampus in male rats under the influence of Simvastatin

2021 ◽  
Author(s):  
Mohammad Saleh Ranaiy ◽  
Farah Farokhi ◽  
Farrin Babaei-Balderlou
Keyword(s):  
Vitamin D ◽  
Total Cholesterol ◽  
Blood Brain Barrier ◽  
Pyramidal Cells ◽  
Brain Barrier ◽  
Male Rats ◽  
Control Group ◽  
Simvastatin Group ◽  
The Brain ◽  
Statistical Results

Abstract Background: Simvastatin is a lipophilic statin and can cross the blood-brain barrier. This study aimed to evaluate the Effect of Simvastatin on pyramidal cells in CA1, CA2, and CA3 regions of the hippocampus in healthy male rats. Method: For the experiment, 36 male Wistar rats with an average weight of 300-250 g were divided into six groups (each group comprised six heads). Groups: 1): Control group, 2): Vitamin D dose 5 µg/kg, 3): Simvastatin group dose 1 mg/kg, 4): Simvastatin group dose 10 mg/kg, 5): Simvastatin group dose 1 mg/kg + vitamin D dose 5 µg/kg, 6): Simvastatin group dose 10 mg/kg + vitamin D dose 5 µg/kg. The duration of drug use was 28 days. At the end of the drug administration period, the animals were slaughtered, then blood samples were taken from the animals (to check TC[1] and LDL-C[2]), and finally, the brain tissue of the animals was extracted to prepare microscopic sections. Results: Statistical results of total cholesterol and LDL-C in rat serum showed that the groups receiving simvastatin 10 mg/kg and simvastatin 10 mg/kg with vitamin D supplement 5 µg/kg were significantly different compared to the control group (P <0.05).Statistical results showed a significant increase (P <0.05) in degenerated cells in the groups receiving simvastatin 10 mg/kg and simvastatin 10 mg/kg with vitamin D supplementation compared with the control group in CA1 and CA2 regions. The statistical results of the study of the percentage of The statistical results of the study of the rate of degenerative cells in CA3 area CA3 of the hippocampus showed that all groups except the vitamin D group had a significant difference (P <0.50) in the percentage of degenerative cells in this region compared to the control group.Conclusion: The results of the present study showed that Simvastatin, due to its lipophilic nature, easily crosses the blood-brain barrier and reduces cholesterol in the brain, thus causing the degeneration of pyramidal cells in the hippocampus.[1] Total cholesterol[2] Low-Density Lipoproteins

scholarly journals Degeneration of pyramidal cells of CA1, CA2, and CA3 are of the hippocampus in male rats under the influence of simvastatin

2021 ◽  
Author(s):  
Mohammad Saleh Ranaiy ◽  
Farah Farokhi ◽  
Farrin Babaei-Balderlou
Keyword(s):  
Vitamin D ◽  
Blood Brain Barrier ◽  
Pyramidal Cells ◽  
Brain Barrier ◽  
Male Rats ◽  
Control Group ◽  
Blood Brain ◽  
Simvastatin Group ◽  
The Brain ◽  
Statistical Results

Abstract Background: Simvastatin is a lipophilic statin and can cross the blood-brain barrier. The aim of this study was to evaluate the effect of simvastatin on pyramidal cells in CA1, CA2, and CA3 regions of the hippocampus in healthy male rats. Method: For the experiment, 36 male Wistar rats with an average weight of 300-250 g were divided into six groups of six (each group comprised six heads). Groups: 1): Control group, 2): Vitamin D dose 5 µg / kg, 3): Simvastatin group dose 1 mg / kg, 4): Simvastatin group dose 10 mg / kg, 5): Simvastatin group dose 1 mg / kg + vitamin D dose 5 µg / kg, 6): Simvastatin group dose 10 mg / kg + vitamin D dose 5 µg / kg. The duration of drug use was 28 days. At the end of the drug administration period, the animals were slaughtered, then blood samples were taken from the animals (to check TC[1] and LDL-C[2]) and finally the brain tissue of the animals was extracted to prepare microscopic sections. Results: Statistical results of total cholesterol and LDL-C in rat serum showed that the groups receiving simvastatin 10 mg / kg and simvastatin 10 mg / kg with vitamin D supplement 5 µg / kg were significantly different compared to the control group (P <0.05).Statistical results showed a significant increase (P <0.05) in degenerated cells in the groups receiving simvastatin 10 mg / kg and simvastatin 10 mg / kg with vitamin D supplementation compared with the control group in CA1 and CA2 regions. The statistical results of the study of the percentage of The statistical results of the study of the percentage of degenerative cells in CA3 region CA3 of the hippocampus showed that all groups except vitamin D group had a significant difference (P <0.50) in the percentage of degenerative cells in this region compared to the control group.Conclusion: The results of the present study showed that simvastatin, due to its lipophilic nature, easily crosses the blood-brain barrier and reduces cholesterol in the brain, thus causing the degeneration of pyramidal cells in the hippocampus.

IMMUNOHISTOCHEMICAL STUDIES OF BLOOD BRAIN BARRIER AFTER ADMINISTRATION OF ABHRAK BHASM IN WISTAR RATS

2021 ◽  
pp. 13-19
Author(s):  
Amita Singh ◽  
Raj Kumar ◽  
S. K. Kannaujia ◽  
Manikrishna Manikrishna ◽  
N. P. Singh
Keyword(s):  
Blood Brain Barrier ◽  
Wistar Rats ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Major Constituent ◽  
Control Group ◽  
Blood Brain ◽  
Biological Studies ◽  
Immunohistochemical Studies ◽  
The Brain

Abhrak bhasma (AB) is a type of bhasma prepared from repeated incineration of mineral mica with decoctions of about 72 herbs. The particle size of Abhrak bhasm has been shown to be in the range of 29-88 nanometers and Fe, Ca, Si, Mg and K are found to be as major constituent. Many drugs developed to treat Central Nervous System (CNS) disorders are unable to reach the brain parenchyma in therapeutically relevant concentrations. The blood brain barrier protects brain parenchyma from the uctuation of plasma composition, from pathogenic agents and maintains homeostasis of the brain parenchyma by restricting non-specic ux of ions, peptides, proteins and even cells into and out the brain. Immunohistochemistry is being widely employed as a tool for biological studies. This study is conducted to examine the change in the continuity of Blood brain barrier by using immunohistochemistry, once Abhrak bhasm drug is given in experimental animal and also to examine the histology of organs. In this study a total of 30 adult albino Wistar rats of approximately 4 months age (approx. 150-200 gms) of either sex selected randomly to see the effect of Abhrak bhasm, an ayurvedic drug on Wistar rats. The rats were weighed, marked and divided into 5 groups each consisting of six animals. In normal control group (Group E), no drug was administered and in rest of the four treated groups (Group-A,B,C,D), Abhrak bhasm @ 36 mg/kg B.wt. was administered orally once in each rat. Brain, liver, kidneys,spleen and blood samples were collected in 10% formalin solution after euthanizing the rats at 0.5,2,6 & 12 hours of Abhrak bhasma drug intervention. The alterations in any of the biochemical parameters are within the tolerable limits of liver and kidney since the dose of abhrak bhasm did not affect liver and kidneys. In the present study, the increase in ALP level may be the result of alterations in metabolisms that occurred without any signicant alteration in histology of liver. After applying the immunohistochemistry with the research markers GFAP, CD 34, S 100, GLUT-1 and RECA-1 on the rats in groups A,B,C and D, there was no change in the intensity of immunohistochemistry, with respect to control. While on applying the Occludin, the intensity of immunohistochemistry was reduced in all the treatment groups as compared to the control group. On the basis of ndings of present study it can be concluded that the therapeutic dose of Abhrak bhasma causes changes at the level of tight junctions present in blood brain barrier in rats which is shown by immunohistochemistry with occludin research marker. There is no toxic effect of drug on different organs of rats as no signicant changes in histology of organs are seen. More studies need to be done to check the permeability of blood brain barrier for Abhrak bhasma drug, like calculating its concentration in brain tissues and other vital organs of rat.

scholarly journals Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model

2020 ◽  
Vol 72 (5) ◽  
pp. 1297-1309
Author(s):  
Dorota Danielak ◽  
Michał Romański ◽  
Anna Kasprzyk ◽  
Artur Teżyk ◽  
Franciszek Główka
Keyword(s):  
Blood Brain Barrier ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Estimation Method ◽  
Rat Plasma ◽  
Brain Barrier ◽  
Male Rats ◽  
Population Pharmacokinetic ◽  
Blood Brain ◽  
The Brain

Abstract Purpose Efficacy of treosulfan, used in the treatment of marrow disorders, depends on the activity of its monoepoxy—(EBDM) and diepoxy compounds. The study aimed to describe the pharmacokinetics of treosulfan and EBDM in the rat plasma and brain by means of mixed-effects modelling. Methods The study had a one-animal-per-sample design and included ninty-six 10-week-old Wistar rats of both sexes. Treosulfan and EBDM concentrations in the brain and plasma were measured by an HPLC–MS/MS method. The population pharmacokinetic model was established in NONMEM software with a first-order estimation method with interaction. Results One-compartment pharmacokinetic model best described changes in the concentrations of treosulfan in plasma, and EBDM concentrations in plasma and in the brain. Treosulfan concentrations in the brain followed a two-compartment model. Both treosulfan and EBDM poorly penetrated the blood–brain barrier (ratio of influx and efflux clearances through the blood–brain barrier was 0.120 and 0.317 for treosulfan and EBDM, respectively). Treosulfan plasma clearance was significantly lower in male rats than in females (0.273 L/h/kg vs 0.419 L/h/kg). Conclusions The developed population pharmacokinetic model is the first that allows the prediction of treosulfan and EBDM concentrations in rat plasma and brain. These results provide directions for future studies on treosulfan regarding the contribution of transport proteins or the development of a physiological-based model.

scholarly journals CT Imaging and Spontaneous Behavior Analysis After Osmotic Blood-Brain Barrier Opening in Wistar Rat

2014 ◽  
pp. S529-S534 ◽  
Author(s):  
P. KOZLER ◽  
V. RILJAK ◽  
K. JANDOVÁ ◽  
J. POKORNÝ
Keyword(s):  
Locomotor Activity ◽  
Brain Edema ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Spontaneous Locomotor Activity ◽  
Brain Barrier ◽  
Male Rats ◽  
Blood Brain ◽  
Significant Difference ◽  
The Brain

In our previous experiments we demonstrated that osmotic opening of the blood brain barrier (BBB) in rats by administration of mannitol into the internal carotid artery leads to cerebral edema. The aim of this study was to confirm objectively the development of brain edema and determine whether it affects spontaneous locomotor activity in rats (SLA). Brain edema was verified by computer tomography (CT) examination of the brain and SLA was observed during open field test. Twenty four adult male rats were divided into four groups of six: (1) control animals (C), (2) controls with anesthesia (CA), (3) controls with sham surgery (CS), (4) experimental – osmotic opening of the BBB (MA). Osmotic BBB disruption manifested by reducing the density of brain tissue (hypodensity), suggesting a higher water content in the brain tissue. SLA was compared between C, CA, CS and MA groups and between MA and CA groups. Significant difference was found only between the control group and MA group. In the first 30 min of the examination, rats after the mannitol administration revealed a marked limitation of spontaneous locomotor activity. Experimental results demonstrated reduction of spontaneous locomotor activity in rats with induced brain edema.

scholarly journals Protection Against Blood-brain Barrier Permeability as a Possible Mechanism for Protective Effects of Thymoquinone Against Sickness Behaviors Induced by Lipopolysaccharide in Rats

2021 ◽  
Vol 16 (2) ◽  
Author(s):  
Rahimeh Bargi ◽  
Mahmoud Hosseini ◽  
Fereshteh Asgharzadeh ◽  
Majid Khazaei ◽  
Mohammad Naser Shafei ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Active Role ◽  
Brain Barrier ◽  
Control Group ◽  
Protective Effects ◽  
Blood Brain ◽  
Immobility Time ◽  
Sickness Behaviors ◽  
Bbb Permeability ◽  
The Brain

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

scholarly journals Blood-brain Barrier Crossing using Magnetic Stimulated Nanoparticles

2021 ◽  
Author(s):  
Jingfan Chen ◽  
Muzhaozi Yuan ◽  
Caitlin Madison ◽  
Shoshana Eitan ◽  
Ya Wang
Keyword(s):  
Blood Brain Barrier ◽  
Pbpk Model ◽  
Superparamagnetic Iron Oxide ◽  
Brain Barrier ◽  
Control Group ◽  
Pbpk Models ◽  
Blood Brain ◽  
The Impact ◽  
The Brain

Due to the low permeability and high selectivity of the blood-brain barrier (BBB), existing brain therapeutic technologies are limited by the inefficient BBB crossing of conventional drugs. Magnetic nanoparticles (MNPs) have shown great potential as nano-carriers for efficient BBB crossing under the external static magnetic field (SMF). To quantify the impact of SMF on MNPs' in vivo dynamics towards BBB crossing, we developed a physiologically based pharmacokinetic (PBPK) model for intraperitoneal (IP) injected superparamagnetic iron oxide nanoparticles coated by gold and conjugated with poly(ethylene glycol) (PEG) (SPIO-Au-PEG NPs) in mice. Unlike most reported PBPK models that ignore brain permeability, we first obtained the brain permeabilities with and without SMF by determining the concentration of SPIO-Au-PEG NPs in the cerebral blood and brain tissue. This concentration in the brain was simulated by the advection-diffusion equations and was numerically solved in COMSOL Multiphysics. The results from the PBPK model after incorporating the brain permeability showed a good agreement (regression coefficient R2 = 0.825) with the in vivo results, verifying the capability of using the proposed PBPK model to predict the in vivo biodistribution of SPIO-Au-PEG NPs under the exposure to SMF. Furthermore, the in vivo results revealed that the brain bioavailability under the exposure to SMF (4.01%) is slightly better than the control group (3.68%). In addition, the modification of SPIO-Au-PEG NPs with insulin (SPIO-Au-PEG-insulin) showed an improvement of the brain bioavailability by 24.47 % in comparison to the non-insulin group. With the SMF stimulation, the brain bioavailability of SPIO-Au-PEG-insulin was further improved by 3.91 % compared to the group without SMF.

scholarly journals The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Peng-Fei Yu ◽  
Wen-Yan Wang ◽  
Gaowa Eerdun ◽  
Tian Wang ◽  
Lei-Ming Zhang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Brain Barrier ◽  
Saline Control ◽  
Control Group ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Danshensu (3-(3, 4-dihydroxyphenyl) lactic acid), a water-soluble active component isolated from the root ofSalvia miltiorrhizaBunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1(verapamil group) or the same volume of normal saline (control group). Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1) by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

Apparent [3H]1,25-dihydroxyvitamin D3 uptake by canine and rodent brain

1983 ◽  
Vol 244 (3) ◽  
pp. E266-E271 ◽  
Author(s):  
M. Gascon-Barre ◽  
P. M. Huet
Keyword(s):  
Vitamin D ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Uptake ◽  
Binding Studies ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Multiple Indicator Dilution ◽  
Blood Brain ◽  
The Brain

The brain uptake of [3H]1,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) was studied during steady-state conditions using the multiple-indicator dilution technique in dogs. The fractional [3H]1,25(OH)2D3 uptake was evaluated at 0.8 +/- 0.15% during a single passage through the dog brain. Evaluation of the [3H]1,25(OH)2D3 uptake by the vitamin D-replete and vitamin D-depleted rat brain indicated that 30 min after its injection, the fractional uptake was not influenced by the vitamin D status of the animals or by the amount of [3H]-1,25(OH)2D3 injected. In the rodent the fractional [3H]-1,25(OH)2D3 brain accumulation was between 0.16 and 0.20%, whereas the brain-to-serum ratio varied between 5 and 6%. Protein-binding studies of serum [3H]1,25(OH)2D3 indicated that, at 37 degrees C, 94.8 +/- 0.4% of the hormone was protein bound 30 min after its intravenous injection. These observations suggest that 1,25(OH)2D3 is able to cross the blood-brain barrier. However, its limited brain uptake in relation to its serum concentration suggests that the hormone does not penetrate freely into the central nervous system and that its brain uptake may be related to the free circulating 1,25(OH)2D3 concentration perfusing the blood-brain barrier.

Chronic immobilization stress induces anxiety-related behaviors and affects brain essential minerals in male rats

2020 ◽  
pp. 1-8
Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  
Keyword(s):  
Immobilization Stress ◽  
Central Area ◽  
Essential Elements ◽  
Male Rats ◽  
Control Group ◽  
Male Wistar Rats ◽  
Swimming Test ◽  
The Brain ◽  
Center Area ◽  
Chronic Immobilization Stress

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.

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