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Neurostimulation is a promising treatment for refractory epilepsy. We studied the effect of cortical stimulation with different parameters in the rat motor cortex stimulation model. High intensity simulation (threshold for motor response - 100 μA), high frequency (130 Hz) stimulation during 1 h decreased cortical excitability, irrespective of the interpulse interval used (fixed or Poisson distributed). Low intensity (10 μA) and/or low frequency (5 Hz) stimulation had no effect. Cortical stimulation appears promising for the treatment of neocortical epilepsy if frequency and intensity are high enough.

The prostate is an accessory sex organ that secretes essential components of semen. High levels of Zn are found both in the prostate and its secretion. In the present study, the effects of environmental stress on zinc levels in the prostate were examined in Wistar male rats exposed to tributyltin chloride (TBTC), an environmental toxicant, by inductively coupled argon plasma–mass spectrometry (ICP-MS) for determination of Zn concentration in lobe-dissectioned specimens and micro-PIXE analysis for determination of site-specific distribution of Zn in prostatic sections. A single oral administration of TBTC to rats at a dose of 90 μmol/kg resulted 14 days later in a decrease in the Zn level in the dorsolateral prostate but not the ventral prostate. The TBTC did not affect the weight of the prostate tissue. Micro-PIXE imaging found Zn both in the lumen and the epithelium of the lateral prostatic tubules. PIXE spot analysis revealed that the epithelium of the control rat contained levels of Zn 4–fold higher than in the lumen and that Zn in the epithelium decreased selectively after TBTC exposure.

The toxic effects of diet containing 10% of C. senna L. fruits or 10% of N. oleander L. leaves or their 1 : 1 mixture (5%+5%) on male Wistar rats treated for 6 weeks were investigated. Diarrhea was a prominent sign of C. senna L. toxicosis. In both phytotoxicities, there were decreases in body weight gains, inefficiency of feed utilization, dullness and enterohepatonephropathy. These findings accompanied by leukopenia and anemia were correlated with alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and concentrations of total protein, albumin, urea and other serum constituents. In both phytotoxicities, the ability of the liver to excrete bilirubin remained unchanged. Feeding the mixture of C. senna L. fruits and N. oleander L. leaves caused more serious effects and death of rats. The implications of these findings are discussed.

It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and cerebral blood flow and microcirculation and improves myocardial ischemia reperfusion injury. This study was designed to investigate the effect of EGb 761 on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats were divided into normal, carbon tetrachloride (CCl₄) and EGb groups, and were given normal saline, CCl₄ and CCl₄ plus EGb 761, respectively, for 10 weeks. Samples were taken from the medial lobe of the rat livers ten weeks later. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were observed under transmission electron microscopy (TEM). The amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry and radioimmunoassay, respectively. Compared with the CCl₄ group, aggregation of blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and space of Disse, injury of endothelial cells and capillization of hepatic sinusoid was significantly reduced in the EGb group. The amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the CCl₄ group, while no significant difference in the amount of NO was observed between the two groups. The results demonstrate that EGb 761 has protective effect on hepatic endothelial cells and hepatic microcirculation in rats with chronic liver injury induced by CCl₄. The mechanisms may involve its inhibition on ET-1, PAF and lipid peroxidation.

The pathogenesis of gentamicin (GM) nephrotoxicity has been shown to involve the generation of oxygen free radicals, and several free radical scavengers have been shown to ameliorate the nephrotoxicity. The seeds and oil of Nigella sativa are reported to possess strong antioxidant properties and was effective against disease and chemically-induced hepatotoxicity and nephrotoxicity. Therefore, in the present work, we have tested whether oral treatment of rats with N. sativa oil (0.5, 1.0 or 2.0 ml/kg/day for 10 days) would ameliorate nephrotoxicity of GM (80 mg/kg/day given intramuscularly and concomitantly with the oil during the last 6 days of treatment). Nephrotoxicity was evaluated histopathologically with a light microscope and by measurement of concentrations of urea, creatinine and total antioxidant status (TAS) in plasma and reduced glutathione (GSH) and TAS in kidney cortex. The results indicated that GM treatment caused moderate proximal tubular damage, significantly increased the concentrations of creatinine and urea, and decreased that of TAS and GSH. Treatment with N. sativa oil produced a dose-dependent amelioration of the biochemical and histological indices of GM nephrotoxicity that was statistically significant at the two higher doses used. Compared to controls, treatment of rats with N. sativa did not cause any overt toxicity, and it increased GSH and TAS concentrations in renal cortex and enhanced growth. The results suggest that N. sativa may be useful in ameliorating signs of GM nephrotoxicity in rats, and pending further experimentation to determine safety and efficacy, may be useful clinically.

The electrical stimulation of meridian points in rats inhibits the withdrawal reflex of the nociceptive tail. Its pain mechanisms are well-documented. Moreover, electroacupuncture (EA) at special abdominal acupoints has been shown to induce a short-term hypoglycemia effect in streptozotocin diabetic rats. The Zusanli and Zhongwan acupoints have been widely used in traditional Chinese medicine to relieve symptoms of diabetes mellitus. It is still unclear whether they can affect extracellular glucose and lactate metabolites at the cellular level. The aim of this study is to evaluate these effects using a rat model for the analysis of extracellular neurochemicals. First, electrical stimulus of 2 ms 2 Hz square pulses (30 minutes) was applied to anesthetized intact rats (n = 7) at the Zusanli points. One and a half hours later, a second electrical stimulus (2 Hz pulses, 30 minutes) was delivered to two of the rats at the same spot. Another two rats received a different stimulation (100 Hz pulses, 30 minutes) at the same location. In the final three rats, a second electrical stimulus of 2 Hz pulses was delivered to non-acupoints. An automated micro-blood sample collector was used to examine the glucose, pyruvate and lactate concentrations. The EA signal has an influence on the biologic process of energy metabolism by mediating dynamic extracellular neurochemical changes. The EA at limb acupoints of the lower limbs induces a decrease in glucose, an increase in lactate metabolites and a decrease in the lactate/glucose ratio. Moreover, the increased lactate/glucose ratio suggests that the cell has an increased anaerobic glucose metabolism.

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

The antioxidant activity and hepatoprotective potential of Cirsium setidens Nakai, a widely used medicinal plant, were investigated. The n-butanol (n-BuOH) fraction of leaves and roots of C. setidens had a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than the other soluble fractions. The n-BuOH fraction of roots of C. setidens had a significant hepatoprotective activity at a dose of 500 mg/kg compared to that of a standard agent. The biochemical results were confirmed by histological observations indicating that C. setidens extract decreased ballooning degeneration in response to CCl₄ treatment. The n-BuOH fraction reduced CCl₄-induced liver injury in rats, and transcript levels of genes encoding antioxidant enzymes such as glutathione peroxidase 1 (GPO1), glutathione peroxidase 3 (GPO3) and superoxide dismutase (SOD1) were elevated in the livers of rats treated with this fraction (500 mg/kg). Based on these results, we suggest that the C. setidens extract has hepatoprotective effect related to its antioxidant activity.

The present study was conducted to clarify the role of the anterior cingulate cortex (ACCX) in acupuncture analgesia. Experiments were performed on 35 female Wistar albino rats weighing about 300 g. Single unit recordings were made from ACCX neurons with a tungsten microelectrode. Descending ACCX neurons were identified by antidromic activation from electrical shocks applied to the ventral part of the ipsilateral PAG through a concentric needle electrode. Cathodal electroacupuncture stimulation of Ho-Ku (0.1 ms in duration, 45 Hz) for 15 min was done by inserting stainless steel needles bilaterally. An anodal silver-plate electrode (30 mm × 30 mm) was placed on the center of the abdomen. Naloxone (1.0 mg/kg, i.v.) was used to test whether changes of ACCX activities were induced by the endogenous opioid system. Data were collected from a total of 73 ACCX neurons. Forty-seven neurons had descending projection to the PAG, and the other 26 had no projections to the PAG. A majority of descending ACCX neurons were inhibited by electroacupuncture stimulation. By contrast, non-projection ACCX neurons were mainly unaffected by electroacupuncture. Naloxone did not reverse acupuncture effects on the changes of ACCX neuronal activities. Acupuncture stimulation had predominantly inhibitory effects on the activities of descending ACCX neurons. Since the functional connection between ACCX and PAG is inhibitory, electroacupuncture caused disinhibition of PAG neurons, whose activity is closely related to descending antinociception to the spinal cord. This disinhibitory effect elicited by acupuncture stimulation is thought to play a significant role in acupuncture analgesia.

Chrysanthemum is a traditional Chinese medicine used in China to treat inflammatory diseases. The total flavonoids Chrysanthemum indicum (TFC) were extracted from the dried bud of Chrysanthemum indicum. Our previous study had demonstrated that TFC was a new class of effective anti-inflammation, analgesia and immunoloregulation agents. In this study, we established an adjuvant arthritis (AA) model by injection of Freund's Complete Adjuvant (FCA) to investigate the effect of TFC on the apoptosis of synoviocytes in AA Rats. Synoviocytes isolated from knee joint of rats were treated with different doses of TFC in vitro. Synoviocytes proliferation was measured by MTT assay, and DNA fragmentations were evaluated on agarose gel electrophoresis. The levels of caspase-3 cleaved fragments were analyzed by Western blot. The annexin V stain assay was used to explore the inhibition of caspase-3 on the amelioration of synoviocytes apoptosis. The results showed that TFC inhibited the proliferation of synoviocytes. Electrophoresis showed higher ladders of DNA bands in the TFC group. Cleaved fragments of caspase-3 were increased significantly. Furthermore, the apoptotic synoviocytes were markedly decreased by the caspase-3 specific inhibitor. These results suggest that TFC could induce synoviocytes apoptosis and suppress proliferation of synoviocytes in adjuvant-induced arthritis rats.

As alternative medicines or dietary supplements, herbal medicines have received increasing interest in recent years. Danggui and Honghua are two of the most popular traditional Chinese herbal medicines. However, little is known about the pharmacokinetics interactions between Danggui/Honghua and prescription drugs. Therefore, the present study was undertaken to investigate the effect of Danggui or Honghua on the gene expression of cytochrome P450 (CYP) using reverse- transcriptase-polymerase chain reaction (RT-PCR) in Wistar rats. Commercial Danggui (0.35 and 0.7 g/kg, twice a day), Honghua (0.35 g/kg or 0.7 g/kg, twice a day) or water (control group) were given to rats (3 rats for each group) for 5 consecutive days. Treatment of rats with 0.7 and 1.4 g/kg per day Danggui or Honghua for 5 days caused mild to strong increase of CYP 3A1 and decrease of CYP 2E1 RNA expression. However, only Honghua (0.7 and 1.4 g/kg per day) induced the increase of CYP 1A2 RNA expression, while CYP 2C11 RNA was unaffected by both Danggui and Honghua. These data demonstrated that Danggui or Honghua affected the expression of hepatic CYP isoforms in the rats; they elevated CYP 1A2 and 3A1 RNA expression but inhibited CYP 2E1 RNA expression. Such alterations may change the therapeutic actions of the drugs metabolized primarily by P450 system when they are co-administered to people with Danggui or Honghua. Therefore, patients should be cautioned about the potential drug-herb interactions between Danggui or Honghua and prescription drugs that were metabolized by CYP1A2, 2E1 and 3A1 isoforms.

Curcumin and saikosaponin A as antioxidants improve antioxidant status. This study investigated the anti-inflammatory and antifibrotic actions of curcumin and saikosaponin A on CCl₄-induced liver damage. Sprague-Dawley rats were randomly divided into control, CCl₄, CCl₄+ curcumin (0.005%; CU), CCl₄ + saikosaponin A (0.004%; SS), and CCl₄ + curcumin + saikosaponin A (0.005% + 0.004%; CU + SS) groups. Carbon tetrachloride (40% in olive oil) at a dose of 0.75 ml/kg was injected intraperitoneally once a week. Curcumin and saikosaponin A were supplemented alone or in combination with diet 1 week before CCl₄ injection for 8 weeks. After 8-week supplementation, histopathological results showed hepatic collagen deposition was significantly reduced in the CU and SS groups, and activated nuclear factor-κ B expression induced by CCl₄ in the liver was significantly inhibited by curcumin and/or saikosaponin A. Hepatic proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 were significantly inhibited, and anti-inflammatory cytokine interleukin-10 was significantly increased by supplementation with curcumin and/or saikosaponin A. Additionally, curcumin and/or saikosaponin A significantly reduced the increased levels of hepatic transforming growth factor-β1 and hydroxyproline after CCl₄ treatment. Therefore, supplementation with curcumin and/or saikosaponin A suppress inflammation and fibrogenesis in rats with CCl₄-induced liver injury. However, the combination has no additive effects on anti-inflammation and antifibrosis.

Cholinergic dysfunction and oxidation stress are the dominant mechanisms of memory deficit in Alzheimer's disease (AD). This study describes how ferulic acid (FA) ameliorates cognitive deficits induced by mecamylamine (MECA), scopolamine (SCOP), central acetylcholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) and amyloid β peptide (Aβ_1-40). This study also elucidates the role of anti-oxidant enzymes and cholinergic marker acetylcholinesterase (AChE) in the reversal of FA from Aβ_1-40-induced cognitive deficits in rats. At 100 mg/kg, FA attenuated impairment induced by MECA and SCOP plus MECA; however, this improvement was not blocked by the peripheral muscarinic receptor antagonist scopolamine methylbromide (M-SCOP). At 100 and 300 mg/kg, FA also attenuated the impairment of inhibitory passive avoidance induced by AF64A. Further, FA attenuated the performance impairment and memory deficit induced by Aβ_1-40 in rats, as did vitamin E/C. FA reversed the deterioration of superoxide dismutase (SOD) and AChE activities, and the glutathione disulfide (GSSG) and glutathione (GSH) levels in the cortex and hippocampus. Vitamin E/C only selectively reversed deterioration in the hippocampus. We suggest that FA reduced the progression of cognitive deficits by activating central muscarinic and nicotinic receptors and anti-oxidant enzymes.

The effect of two different concentrations of povidone-iodine (PVI) solution, an antiseptic, on joint synovium was investigated. In Group I, 0.05 ml of 10% PVI was used, while in Group II, 0.05 ml of 2.5% of PVI was used. PVI solution was injected twice into both knee joints with one week interval. Ten rats were used as control and 70 rats as experimental.

In the two experimental groups four rats were sacrificed after 6, 12, 24 hours and three day and six rats at the end of the week after the second PVI injection. Synovial reaction was assessed histologically in both groups, based on the pathological parameters.

The results suggest that intra-articular injection of 10% and 2.5% PVI induces synovitis with focal ulceration which gradually subsides, and finally, the synovium becomes normal, though various degrees of subsynovial dense fibrosis complication arise.

Introduction: Fractures are common in the old and are associated with increased morbidity. The pain of fractures and surgery can be managed using NSAIDs, but this may result in impaired healing. The inflammatory stage of bone healing is responsible for laying the foundation for subsequent proliferative stages. This may be the stage when NSAIDs may have their greatest impact and it is unclear if avoiding NSAIDs in this stage would result in differences in healing or whether different molecules have varied responses. This study sought to determine the differences in the histomorphometry of fracture callus in older rats when diclofenac and celecoxib were avoided in the first week after a fracture.

Methods: Fractures of the tibia were induced in 43 15-month-old (equivalent to 50 human years) rats which were then allocated to receive either diclofenac or celecoxib. Each group was further subdivided into early or late subgroups of 10 animals each receiving the study medication from the day after the fracture or eight days later, respectively. Histological and stereological examination of the callus on days 21 and 42 enabled comparison of histological grades, tissue proportions and cellular densities.

Results: The histological grade and amount of bone increased and the amount of cartilage reduced in all groups. The group that received celecoxib early had the least proportion of bone. The osteocyte and chondrocyte cellular densities increased in all groups across both time points.

Conclusion: Administration of celecoxib in the early fracture period in the old is associated with poorer histological grades, lower proportions of bone and increased cellularity which may result in delayed union of the fracture. Use of selective COX-2 inhibitors is discouraged for the management of pain in older patients with fractures especially in the first seven days.

In order to have a tool to empirically test the ideas derived from a theoretical model, we extended a protocol for evaluation of episodic-like memory in rats, based on the triad "what, where, context" for definition of memories. As with the computational model, our intention was for the animal being tested to store a specific number of object-place-context configurations as different memories, which would then be retrievable from cues. The aim of this work was to evaluate the influence of the number of configurations to be memorized on the performance of the task. Sixty-five Wistar male rats were evaluated. In accordance with previous work, for two configurations, the recognition index was indicative of recognition of the element mismatching the original memory (mean = 0.28; SEM = 0.12). The recognition index for three configurations was lower (mean = 0.15; SEM = 0.10), evidencing less recall with increasing requirements. The results also showed a trend toward recognition of novelty for the first and the last memory when evaluating three configurations (a "U" shape in the exploratory preference's curve), showing the primacy and recency effects typical of memory both in humans and animals. Nonetheless, the data presented a high inter-subject variability which makes the test non-robust for small groups. However, if used before and after a treatment for a same subject, we suggest that the protocol presented in this work can be a useful behavioral test for the evaluation of episodic-like memory in rats in terms of a variable task demand.

Dry eye syndrome (DES), is one of the most common and irritating ocular diseases in humans and animals due to deficits in quantities or/and quality of tear film. In this study, a rat model of experimental DES has been developed using the cholinergic inhibitor, scopolamine hydrobromide (SCOP), at the dose of 25mg/rat/day via subcutaneous injection, for a consecutive 21 days without low humidity environment. Clinical ophthalmic evaluations were performed by tear volume assessment using endodontic paper point, slit-lamp biomicroscope, and fluorescein staining at day 0, 7, 14, and 21 post-inductions. The results of ophthalmic examination showed that rats with SCOP treatment reduced about 40% of tear secretion. Half of the SCOP-treated rats exhibited diffuse corneal fluorescein staining involving 80% of the corneal surface, minimal keratoconjunctivitis, roughened corneal surface and thin corneal epithelium under histopathological examination. About 30% of the rats showed variable infiltration of lymphocytes in between the tubular acinar glands. This animal model with significant reduction of tear production and diffuse corneal fluorescein staining in rats could be used for the preclinical assessment of therapeutic interventions.

Glaucoma and retinal degenerations are two important ocular diseases that often cause massive impacts to vision in both humans and animals. Rat models are commonly used to explore the complex pathophysiology and potential treatments of these diseases. The models of high intraocular pressure (HIOP)-induced retinal ischemia-reperfusion imply the ischemic outcome weight on the inner retina layers (including the nerve fiber layer, retinal ganglion cell (RGC) layer, inner plexiform layer (IPL), and inner retinal layer (INL)) that eventually progressed to the outer retinal layers. Depending on the duration (cycles) of ischemic treatment, more glaucoma pathological change signs may be exhibited more obviously with time. The model requires a short ischemic treatment and anticipates an adequately long period of disease manifestation. To investigate photoreceptor-led retinal degeneration, rat models for light-induced retinopathy are commonly used and it is predominantly attributed to the photoreceptor cells damage of ONL and OPL loss by high intensity of light exposure. This model unraveled the pathophysiological impairment of phototransduction as well as disease mechanisms involving oxidative stress and inflammatory process of the outer retinal layer. With the knowledge gained from the research using these animal models, better understanding of the disease mechanisms in terms of its pathophysiology and molecular changes can be achieved. Besides, the rat models can serve as the key basis for further investigation into the therapeutic or preventive perspectives of these retinopathies.

Cortical spreading depression (CSD) is a pathophysiological phenomenon. There are sufficient evidences to prove that CSD plays an important role in some neurological disorders. However, exact mechanisms of its initiation and propagation are still unclear. Previous studies showed that glutamate receptors could be concerned with CSD, but those studies were mostly performed oriented to ionotropic glutamate receptors (iGluRs). There is relatively little report about effects of metabotropic glutamate receptors (mGluRs) on CSD. Here, we applied optical intrinsic signal imaging (OISI) combined with direct current (DC) potential recording to examine influences of some mGluRs antagonist (or agonist) on CSD propagation in rat's brain, to indirectly validate actions of some mGluRs on CSD. We found that N-acetyl-L-aspartyl-L-glutamate (NAAG, an agonist at mGluR3) inhibited the propagation of CSD, and the inhibition was gradually developed with time. However, 6-methyl-2-phenylethynyl-pyridine (MPEP, an antagonist of mGluR5) did not produce any significant alterations with the CSD propagation. Our findings suggest that mGluR3 could play an important role in the CSD propagation, but the activity of mGluR5 was comparatively weak. These findings can help to understand the propagation mechanism of CSD, and consider the therapy of some neurological diseases involved with CSD.

The influence of ischemia–reperfusion (I/R) action on pancreatic blood flow (PBF) and the development of acute pancreatitis (AP) in laboratory rats is evaluated in vivo by using the laser speckle contrast imaging (LSCI). Additionally, the optical properties in norm and under condition of AP in rats were assessed using a modified integrating sphere spectrometer and inverse Monte Carlo (IMC) software. The results of the experimental study of microcirculation of the pancreas in 82 rats in the ischemic model are presented. The data obtained confirm the fact that local ischemia and changes in the blood flow velocity of the main vessels cause and provoke acute pancreatitis.