Space Of Rats Research Articles

Spontaneous atrial fibrillation occurrence following transesophageal atrial burst pacing in rats

Abstract Purpose Animal models play a crucial role in elucidating the complex pathophysiology of atrial fibrillation (AF) and in identifying and testing novel antiarrhythmic strategies. We aimed to develop and characterize a new experimental rat model of AF, induced by long-term transesophageal atrial electrical stimulation, and to investigate whether the "AF begets AF" concept applies to small rodent hearts. Method Twelve adult male Wistar rats were randomized into two groups: Sham (n = 5) and AF (n = 7). All rats were implanted at the beginning of the study with ECG radiotelemetry devices and underwent continuous ECG monitoring throughout the study. To induce AF, the rats in the AF group underwent atrial pacing for 10 consecutive days (15 successive cycles of stimulation/day, 20 s each, with a free interval of 5 min between cycles; 4,000 stimuli/min, stimulus duration 6 ms, voltage 3 V above the diastolic threshold). A similar procedure was applied to the Sham group, but without performing the actual electrical stimulation. The number and duration of spontaneous AF episodes were evaluated based on continuous ECG monitoring prior to, during, and for one week after transesophageal atrial pacing. The inducibility of AF and the occurrence and duration of spontaneous AF episodes were evaluated and compared between the two groups. Results Atrial fibrillation was induced in 85.7% of the rats subjected to atrial electrical pacing (Figure, A), with an average global inducibility of 44.0% ± 16.9% and a mean AF duration of 123.2 ± 96.3 s. No induced or spontaneous AF episodes were recorded in any of the Sham animals. In the AF group, none of the animals presented spontaneous AF before transesophageal atrial pacing. However, in the AF rats, after atrial electrical stimulation initiation, the number of atrial premature beats significantly increased (21.3 ± 6.8 / 24-h post-stimulation vs. 7.3 ± 6.5 / 24-h at baseline; p< 0.01; Figure, B), and all rats presented spontaneous AF episodes (Figure, C). At the end of the study, AF rats presented a total number of 23.9 ± 2.3 AF episodes / 24-h (Figure, D), with a mean AF burden of 337.7 ± 25.06 s / 24-h. Conclusions Our data demonstrate that, despite the small size of the atria, the "AF begets AF" concept is applicable in small rodents. The study presents a novel rat model of AF, in which spontaneous AF occurs following long-term atrial electrical stimulation. Given that the model is relatively rapid and easy to implement, it provides a setup for further investigation of AF pathophysiology, and for identifying and testing novel therapeutic strategies for AF.Figure 1

Development of a Surgical Technique for Subretinal Implants in Rats.

Retinal degeneration, such as age-related macular degeneration (AMD), is a leading cause of blindness worldwide. A myriad of approaches have been undertaken to develop regenerative medicine-based therapies for AMD, including stem cell-based therapies. Rodents as animal models for retinal degeneration are a foundation for translational research, due to the broad spectrum of strains that develop retinal degeneration diseases at different stages. However, mimicking human therapeutic delivery of subretinal implants in rodents is challenging, due to anatomical differences such as lens size and vitreous volume. This surgical protocol aims to provide a guided method for transplanting implants into the subretinal space in rats. A user-friendly comprehensive description of the critical steps has been included. This protocol has been developed as a cost-efficient surgical procedure for reproducibility across different preclinical studies in rats. Proper miniaturization of a human-sized implant is required prior to conducting the surgical experiment, which includes adjustments to the dimensions of the implant. An external approach is used instead of an intravitreal procedure to deliver the implant to the subretinal space. Using a small sharp needle, a scleral incision is performed in the temporal superior quadrant, followed by paracentesis to reduce intraocular pressure, thereby minimizing resistance during the surgical implantation. Next, a balanced salt solution (BSS) injection through the incision is carried out to achieve focal retinal detachment (RD). Lastly, insertion and visualization of the implant into the subretinal space are conducted. Post-operative assessment of the subretinal placement of the implant includes imaging by spectral domain optical coherence tomography (SD-OCT). Imaging follow-ups ascertain the subretinal stability of the implant, before the eyes are harvested and fixated for histological analysis.

Improved intervertebral bone union in ALIF rat model with porous hydroxyapatite/collagen combined with platelet-rich plasma

BACKGROUND CONTEXTPlatelet-rich plasma (PRP) can accelerate bone union in spinal fusion surgery with an autogenous bone graft. However, it is unclear whether bone union can be obtained by using artificial bone and PRP together in spinal interbody fusion surgery. PURPOSEThis study aimed to determine whether interbody fusion can be achieved by transplanting porous hydroxyapatite/collagen(HAp/Col) which is an artificial bone material frequently used in spinal fusion surgery, together with PRP in the intervertebral disc space in rats. STUDY DESIGN AND SETTINGA controlled laboratory study. METHODSA total of fourty 10-week old Sprague-Dawley rats were used in this study and assigned to three groups as follow: disc curettage only (control group, n=10), disc curettage + HAp/Col transplant (H group, n=10), and disc curettage + HAp/Col + PRP transplant (H+P group, n=10). The other 10 rats were sacrificed as blood donors for acquisition of PRP. Microcomputed tomography (μCT) examinations were performed to evaluate bone union, bone volume (BV), and bone mineral density (BMD) at 4, 8, and 12 weeks following surgery. Twelve weeks postoperatively, each group of three of L4–L5 spines was harvested to perform histological examination (hematoxylin & eosin stain) and the others were subjected to biomechanical testing (compression properties). RESULTSThe platelet count in PRP was approximately 4.1 times greater than that in whole blood (260.6±26.2 × 104 mg/dL and 64.3±2.9 × 104 mg/dL in PRP and whole blood, respectively). All the L4–L5 lumbar discs were fused in the H+P group, whereas only one case was fused in the H group and none in the control group at 12 weeks after surgery. BV was significantly higher in the H+P group than in the H group or control groups (both p<.01), although BMD was not significantly different among the three groups. Upon histological analysis, mature bone formation was observed at the transplanted space in all cases in the H+P group, whereas fibrous tissue was observed at the location in the H and control groups. Regarding biomechanical properties, the ultimate load to failure was significantly higher in the H+P group than in the H group or control group (p=.021 and .013, respectively), although stiffness was not significantly different between the three groups. CONCLUSIONThe combination of porous HAp/Col and PRP at an appropriate concentration can promote bone union in the intervertebral disc space without using an autologous bone graft in the rat model. Bone tissue formation was histologically confirmed, and it was mechanically strong. CLINICAL SIGNIFICANCEThis preclinical study showed that porous HAp/Col, when combined with PRP at an appropriate concentration, can induce bone union without autologous bone grafts. The results may eliminate the need for autologous bone collection for spinal fusion surgery in the future.

Histological, metabolic, and inflammatory changes in the renal tissues of high-fat diet-induced obese rats after vitamin D supplementation

PurposeObesity is a major risk factor for chronic renal fibrosis and kidneys’ structural and inflammatory impairments. This study aims to examine the possible therapeutic effects of vitamin D supplementation against renal inflammatory and kidney’s structural fibrosis and degeneration.Design/methodology/approachForty male Wistar rats were divided into two groups for 16 weeks: normal diet (ND) and high-fat diet (HFD); then, each group was subdivided into two groups including ND, ND + vitamin D and HFD, HFD + vitamin D. Vitamin D supplementation was done for five weeks at 500 IU/kg dosage. Renal tissue concentrations of tumor necrosis factor (TNF)-α, interleukin 6, interleukin 1 beta, monocyte chemoattractant protein (MCP)-1 and transforming growth factor-beta (TGF-β), serum values of lipids, markers of glucose homeostasis and urea, creatinine and uric acid and renal tissue histological and structural changes were determined.FindingsHFD feeding caused remarkable histological and structural changes including higher TNF-α, MCP-1 and TGF-βconcentrations in renal tissues of rats, whereas vitamin D has potent anti-inflammatory effects (P= 0.036, 0.047 and 0.02, respectively). Vitamin D administration also reduced urea and uric acid concentrations (P= 0.023 and 0.049, respectively). Moreover, vitamin D reduced glomerulomegaly, reduced lipid accumulation and limited dilated Bowman’s space in rats and improved glycemic status by increasing insulin (P= 0.04) and reducing insulin resistance (P= 0.006).Research limitations/implicationsThe current study has some limitations. It was better to measure the level of inflammatory cytokines’ expression in the kidney tissues. Additionally, the measurement of baseline values of inflammatory cytokines was not possible because of the possibility of animals’ drop-out.Practical implicationsAccording to the study findings, vitamin D treatment in the current report showed a significant therapeutic role in reducing inflammation, improving glycemic and lipid abnormalities and structural and histological modifications in renal tissues of rats. These findings have a great value because after confirming in a human model, vitamin D can be suggested as a potential therapeutic tool in clinical practice.Social implicationsAfter being confirmed by other animal or human researches, the results of the current work could have great social implications by reducing the prevalence of obesity-related renal complications and highlighting the beneficial roles of vitamin D.Originality/valueTo the best of the authors’ knowledge, this is the first study to investigate the histological and inflammatory changes in the kidneys and metabolic parameters in the HFD induced rats and also clarified the therapeutic roles of vitamin D in ameliorating the inflammatory, histological, metabolic and functional changes in the kidneys of obese rats.

The place-cell representation of volumetric space in rats

Place cells are spatially modulated neurons found in the hippocampus that underlie spatial memory and navigation: how these neurons represent 3D space is crucial for a full understanding of spatial cognition. We wirelessly recorded place cells in rats as they explored a cubic lattice climbing frame which could be aligned or tilted with respect to gravity. Place cells represented the entire volume of the mazes: their activity tended to be aligned with the maze axes, and when it was more difficult for the animals to move vertically the cells represented space less accurately and less stably. These results demonstrate that even surface-dwelling animals represent 3D space and suggests there is a fundamental relationship between environment structure, gravity, movement and spatial memory.

Rats provide a superior model of human stress erythropoiesis

Mouse models are widely used to study human erythropoiesis in vivo. One important caveat using mouse models is that mice often develop significant extramedullary erythropoiesis with anemia, which could mask important phenotypes. To overcome this drawback in mice, here we established in vitro and in vivo rat models for the studies of stress erythropoiesis. Using flow cytometry-based assays, we can monitor terminal erythropoiesis in rats during fetal and adult erythropoiesis under steady state and stress conditions. We used this system to test rat erythropoiesis under phenylhydrazine (PHZ)-induced hemolytic stress. In contrast to mice, rats did not have an increased proportion of early-stage erythroid precursors during terminal differentiation in the spleen or bone marrow. This could be explained by the abundant bone marrow spaces in rats that allow sufficient erythroid proliferation under stress. Consistently, the extent of splenomegaly in rats after PHZ treatment was significantly lower than that in mice. The level of BMP4, which was significantly increased in mouse spleen after PHZ treatment, remained unchanged in rat spleen. We further demonstrated that the bone marrow c-Kit positive progenitor population underwent a phenotype shift and became more CD71 positive and erythroid skewed with the expression of maturing erythroid markers under stress in rats and humans. In contrast, the phenotype shift to an erythroid-skewed progenitor population in mice occurred mainly in the spleen. Our study establishes rat in vitro and in vivo erythropoiesis models that are more appropriate and superior for the study of human stress erythropoiesis than mouse models.

Assessment of Neurological Toxicity of Hydroxyethyl Starch 130/0.4 Injected in the Intrathecal Space in Rats.

Epidural blood patch is the procedure of choice to relieve postdural puncture headache. Hydroxyethyl-starch (HES) has been proposed as a patch in some circumstances such as in the case of hematological disease due to the theoretical risk of neoplastic seeding to the central nervous system. Acute neurological HES toxicity has been excluded by a previous animal study, but the long-term neurological toxicity has not been evaluated. Rats were randomly assigned to one of three groups: no intrathecal injection, 20 μL of intrathecal saline, or a 20-μL intrathecal HES (6% hydroxyethyl starch 130/0.4) administered via a cervical puncture. Clinical daily rat activity was measured before and after dural puncture by actinometry. The rats were killed at day 28, and the spinal cord was surgically removed and stained with hematoxylin-phloxine-saffron for gross and microscopic examination. Eleven rats underwent dural puncture without injection, 11 were injected with normal saline, and 12 received intrathecal HES. No clinical or actimetric changes (total distance traveled, number of direction changes, and number of rearings) were observed up to one month after injection. Nonspecific histopathological changes were equally observed in all groups. The results of the current study indicate that intrathecal injection of HES in rats does not induce any clinical or histopathological evidence of long-term neuronal toxicity. Further safety studies in animals are warranted before HES might be considered a safe alternative to the classic epidural blood patch.

Spontaneous atrial fibrillation after long-term transesophageal atrial burst pacing in rats. Technical and procedural approach to a new in vivo atrial fibrillation model

Spontaneous atrial fibrillation after long-term transesophageal atrial burst pacing in rats. Technical and procedural approach to a new in vivo atrial fibrillation model

Dermal pharmacokinetics of pyrazinamide determined by microdialysis sampling in rats

Studies have demonstrated the efficacy of pyrazinamide (PZA) against stages of the Leishmania parasite that causes cutaneous leishmaniasis. Although PZA is widely distributed in most body fluids and tissues, the amount of drug reaching the skin is unknown. This study aimed to investigate the pharmacokinetics of PZA in rat dermal tissue by dermal microdialysis. Skin pharmacokinetics was assessed by implanting a linear microdialysis probe in the dermis of ten rats. In addition, blood samples were collected to assess plasma pharmacokinetics. Unbound microdialysate (N = 280) and plasma (N = 120) concentrations following single intravenous doses of 25 mg/kg or 50 mg/kg PZA were quantified by a validated HPLC method. Probe calibration was performed by retrodialysis. Non-compartmental analysis and non-linear mixed-effects modelling were performed using WinNonlin and NONMEM v.7.3. PZA rapidly permeated into the dermis and reached high levels, with mean maximum concentrations (Cmax) of 22.4 ± 7.1 µg/mL and 48.6 ± 17.3 µg/mL for the two doses studied. PZA showed significant distribution to the skin (fAUCdermal/fAUCplasma = 0.82 ± 0.31 and 0.84 ± 0.25 for 25 mg/kg and 50 mg/kg doses, respectively). Active unbound concentrations in dermal tissue reached lower levels than free plasma concentrations, indicating that free PZA levels in plasma were in equilibrium with tissue levels. These results showed equivalent unbound drug tissue concentrations and corresponding unbound plasma levels. This study shows that PZA distributes rapidly into dermal interstitial fluid space in rats and therefore may be a potential agent in the treatment of cutaneous leishmaniasis.

A Novel Laparoscopic Surgery Model with a Device to Expand the Abdominal Working Space in Rats: The Influence of Pneumoperitoneum and Skin Incision Length on Postoperative Inflammatory Cytokines

ABSTRACTPurpose: Experimental models of laparoscopic surgery generally use large animals owing to a sufficient abdominal working space. We developed a novel laparoscopic surgery model in rats. We performed intestinal anastomosis to demonstrate the feasibility and reliability of this model. Materials and Methods: We designed a device for rats that expanded the abdominal working space and allowed us to manipulate the intraperitoneal organs by hand under direct vision with pneumoperitoneum. We performed small bowel resection and intestinal anastomosis in rats using this model. To elucidate the effects of pneumoperitoneum and skin incision length, rats were randomly divided into four groups with differing surgical techniques: small incision group, large incision group, small incision + pneumoperitoneum group, and large incision + pneumoperitoneum group. Intraoperative abdominal pressure and postoperative cytokines were measured. Results: One experimenter completed small bowel resection and hand-sewn anastomosis under direct vision without any difficulties or assistance. Carbon dioxide pneumoperitoneum was maintained at 8–10 mmHg during surgery in both pneumoperitoneum groups. Necropsies revealed no evidence of anastomotic leakage at 24 h after surgery. The interleukin-6 and C-reactive protein concentrations were significantly greater in large incision group than in small incision group, but were not significantly different between small incision + pneumoperitoneum group and small incision group. These cytokines concentrations were the greatest in large incision + pneumoperitoneum group. Conclusions: Our laparoscopic surgery model in rats is a simple and reliable experimental model. The length of skin incision might be a more influential determinant of surgical invasiveness than pneumoperitoneum.

Prominent differences in left ventricular performance and myocardial properties between right ventricular and left ventricular-based pacing modes in rats

Biventricular pacing is an important modality to improve left ventricular (LV) synchronization and long-term function. However, the biological effects of this treatment are far from being elucidated and existing animal models are limited and demanding. Recently, we introduced an implanted device for double-site epicardial pacing in rats and echocardiographically demonstrated favorable effects of LV and biventricular (LV-based) pacing modes typically observed in humans. Here, this new animal model was further characterized. Electrodes were implanted either on the right atria (RA) and right ventricle (RV) or on the RV and LV. Following recovery, rats were either used for invasive hemodynamic measurements (pressure-volume analysis) or exposed to sustained RV vs. biventricular tachypacing for 3 days. RV pacing compromised, while LV-based pacing modes markedly enhanced cardiac performance. Changes in LV performance were associated with prominent compensatory changes in arterial resistance. Sustained RV tachypacing increased the electrocardiogram QTc interval by 7.9 ± 3.1 ms (n = 6, p < 0.05), dispersed refractoriness between the right and left pacing sites and induced important molecular changes mainly in the early-activated septal tissue. These effects were not observed during biventricular tachypacing (n = 6). Our results demonstrate that the rat is an attractive new model to study the biological consequences of LV dyssynchrony and resynchronization.

A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats.

Chronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.

Transport of Azithromycin into Extravascular Space in Rats.

Recent clinical trials showed a prolonged retention of subinhibitory concentrations of unbound azithromycin in the interstitial fluid of soft tissues despite the fact that azithromycin is extensively distributed in tissues. In these clinical trials, interstitial fluid samples were obtained by using the microdialysis method, and it was established that drug concentrations represent protein-unbound drug concentrations. The present study was designed to measure total azithromycin concentrations in the interstitial fluid of the skin of rats by directly collecting interstitial fluid samples from a pore formed on the skin by a dissolving microneedle array. The total azithromycin concentrations in interstitial fluid of the skin were about 4 to 5 times higher than those in plasma throughout the experimental period, and stasis of the azithromycin concentration in interstitial fluid was observed when the concentration of azithromycin in plasma was at the lower limit of quantification. In addition, the skin/plasma concentration ratio transiently increased after dosing (from 4.3 to 83.1). Our results suggest that azithromycin was trapped inside white blood cells and/or phagocytic cells in not only blood but also interstitial fluid, resulting in a high total azithromycin concentration and the retention of its antimicrobial activity at the primary infection site. The stasis of azithromycin in interstitial fluid and skin would lead to long-lasting pharmacological effects (including those against skin infection) at concentrations exceeding the MIC.

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid.

Effect of Simvastatin on induced apical periodontitis in rats: a tomographic and biochemical analysis

Abstract Introduction Simvastatin is one of several statins that are used to treat hypercholesterolemia, and in dentistry, few studies have attempted to associate the administration of this compound with bone repair. Objective To evaluate the effect of simvastatin on the progression of induced apical periodontitis in rats. Material and method To this end, 36 male Wistar rats were divided into 3 groups (N=12): Induced Apical Periodontitis Associated with Simvastatin Group (APSG N=12), Induced Periodontitis Apical Induced Group (APG N=12) and Negative Control Group (CG). On the first day, APG and APSG were anesthetized, and the coronal opening of the mandibular first molar was performed. For thirty days, the APSG received 6 mg of simvastatin daily via gavage. On the thirty-first day, all groups underwent blood collection and euthanasia. The jaws were removed and fixed in formalin. CT scans were performed to measure the periapical regions. In addition, the body mass and lipid profile were analyzed. The data were subjected to statistical analysis (ANOVA and Tukey’s test). Result The APG (3.42±0.65) showed the highest perimeters for the space periapical ligament, followed by APSG (1.54±0.78) and CG (0.64±0.24) (p&lt;0.05). The lipid profile revealed the effect of simvastatin on the amount of glucose, triglycerides, HDL, and VLDL (p&lt;0.05). Body mass APG showed the most weight gain (264.75±44.11), followed by CG (252.00±44.36) and APSG (245.41±42.56). The three groups showed significant differences in decreasing order (p&lt;0.05). Conclusion The use of simvastatin decreased the progression of the increasing periapical ligament space in rats.

Anti-chronic stress effect of bone marrow mesenchymal stem cell transplantation in rats with spinal cord injury

Objective To investigate the anti-chronic stress effect of bone marrow mesenchymal stem cell (BMSCs) transplantation in rats with spinal cord injury. Methods Forty-eight adult SD rats were divided into control group, model group and treatment group according to the random number table, with 16 rats each. In model and treatment groups, lower thoracic (T10) spinal cord injury were constructed using the modified Allen's method. In control group, only laminectomy was performed. After 7 days, 100 μl Hank's buffer suspension containing 1.0×106 BMSCs was injected into the subarachnoid space of L4-5 intervertebral space of rats in control group and treatment group. While in model group, only the equal volume of Hank's buffer was used. Basso-Beattie-Bresnahan (BBB) scale was performed to evaluate hindlimb motor function in rats. At postoperative 14 and 28 days, blood samples were collected to measure adrenocorticotropic hormone (ACTH), norepinephrine (NE), epinephrine (E) and corticosterone (CORT) using the ELISA method; brains were harvested for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor proteins GluR1 and GluR2 immunohistochemical staining. Results After injury, BBB scores in model and treatment groups were similar, but both were lower than that in control group (P<0.05). After BMSCs transplantation, BBB score in treatment group [21 d: (9.85±0.82)points and 28 d: (11.23±0.68)points] improved continuously compared to model group [21 d: (8.42±0.39)points and 28 d: (8.84±0.25)points], but all were lower than that in control group [(21.00±0.00)points, P<0.05]. ACTH contents in model and treatment groups at 14 d [(104.80±6.16) and (98.50±4.07)pg/ml] and 28 d [(101.40±2.33) and (96.50±2.28)pg/ml] were higher than those in control group [(90.40±11.36) and (83.20±5.22)pg/ml] (P<0.05). CORT contents in model and treatment groups [(44.40±1.44) and (43.30±1.17)ng/ml] was lower than that in control group [(48.20±2.27)ng/ml] at 14 d, but were found to be elevated [(70.40±1.90) and (61.40±1.83)ng/ml] compared to control group [(46.40±1.49)ng/ml] at 28 d (P<0.05). Meanwhile, the CORT content in treatment group was lower than that in model group (P<0.05). Changes in NE and E contents among the groups were similar with ACTH. Immunohistochemical staining suggested the amounts of GluR1 and GluR2 positive cells in treatment group lowered compared to control group (P<0.05), but increased in model group compared to control group (P<0.05). Conclusion BMSCs transplantation can improve the hindlimb motor function, contribute to reducing the secretion of stress-related hormones ACTH, CORT, NE and E, and down-regulate the expression of AMPA receptor proteins GluR1 and GluR2 in rats with spinal cord injury, suggesting a potential role in anti-chronic stress. Key words: Spinal cord injuries; Mesenchymal stem cell transplantation; Stress

Implantation of the Auditory Nerve via the Middle Ear Cavity in Rats with Partial Hearing Preservation

The aim of this study was to evaluate the residual hearing function and cochlear morphology after auditory nerve implantation via middle ear spaces in rats. A titanium rod (1.5 mm long and 0.3 mm thick) coated with Parylene was inserted in the cochlear apex in the direction of the modiolus in 9 Wistar rats. Auditory brainstem-evoked responses to tone bursts at 2, 8, 12 and 32 kHz were recorded before surgery and on postoperative days 0, 2, 15 and 30. Eight cochleas were examined microscopically. The rod was inside the modiolus in 4, and partly or totally outside the modiolus in 4 animals. Residual hearing was present in all cases. The average threshold shift in cochleas with modiolar implant was 39 ± 11.2, 54 ± 9.7, 48 ± 20.3 and 43 ± 21.3 dB SPL on postoperative days 0, 2, 15 and 30, respectively. The transmodiolar approach allows a minimally invasive cochlear implantation and a partial hearing preservation.

Adrenaline aggravates lung injury caused by liver ischemia-reperfusion and high-tidal-volume ventilation in rats.

BackgroundWe often administer adrenaline to improve hypotension of patients undergoing systemic inflammation that is not treated with volume resuscitation. The effects of adrenaline on injured lungs during shock status have not been elucidated. We previously demonstrated that hepatic ischemia–reperfusion followed by high-tidal-volume ventilation-induced systemic inflammation, hypotension, and lung injury in rats. Using this animal model, we investigated the effects of adrenaline on lung injury and hemodynamics.MethodsAnesthetized rats were ventilated and underwent hepatic inflow interruption for 15 min twice. After the second liver ischemia–reperfusion, the tidal volume was increased to 24 ml · kg−1 body weight from 6 ml · kg−1, and 12 rats in each group were observed for 360 min after reperfusion with or without continuous intravenous adrenaline administration. Extra fluid was administered according to the decline in the arterial blood pressure.ResultsAdrenaline administration significantly reduced the volume of intravenous resuscitation fluid. The wet-to-dry weight ratio of the lungs was higher (7.53 ± 0.37 vs. 4.63 ± 0.35, P < 0.001), the partial oxygen pressure in arterial blood was lower (213 ± 48 vs. 411 ± 33, P = 0.004), and the tumor necrosis factor-α concentration in bronchoalveolar lavage (BAL) fluid was higher (102.64 ± 100.22 vs. 101.91 ± 100.27, P = 0.015), with adrenaline. Histopathological examinations revealed marked exudation in the alveolar spaces in rats receiving adrenaline.ConclusionsContinuous administration of adrenaline partially prevented a rapid decline in blood pressure but deteriorated lung injury in a rat model of liver ischemia–reperfusion with high-tidal-volume ventilation. A possibility that adrenaline administration aggravate ventilator-induced lung injury during systemic inflammation should be considered.

Wound healing suppressant effect of vincristine reversed by vitamin A: an experimental study

Background: Use of antineoplastic drugs pre and postoperatively have shown to adversely affect the healing of surgical wounds. Vincristine is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that vincristine impairs skin wound healing. Methods: In this study we investigated the effect of vitamin A on vincristine induced suppression of healing in two wound models, viz: incision and dead space in rats. Hydroxyproline (measure of collagen) was estimated colorimetrically and breaking strength of the wound and granulation tissue was measured. Results: Vincristine (60 mcg/Kg intraperitoneally, on the 3 rd wounding day) significantly reduced breaking strength in both incision and dead space wound models. Vitamin A (5000 I.U, Subcutaneously on alternate days) by itself did not alter any of the parameters studied but reversed the suppressant effects of vincristine on wound healing. Conclusions: Vitamin A by itself produced little effect on healing except a modest increase in granulation mass. But it significantly reversed the healing suppressant effects of vincristine.

Efecto hiperalgésico de la fentolamina por vía subaracnoidea en ratones

Background and objectivesPainful phenomenon is one of the most important and complex experiences. Phentolamine is a non-selective alpha-adrenergic antagonist. The objective of this study was to compare the effect of increasing doses of phentolamine into subarachnoid space in rats in the modulation of painful phenomenon. MethodsEighty four male Wistar rats were divided into formalin and plantar incision groups, subdivided into six subgroups (n=7). Control group (CG) received only saline (10μL); active subgroups received phentolamine 10μg (GF10), 20μg (GF20), 30μg (GF30), 40μg (GF40), and 50μg (GF50). In formalin group, pain was induced by injection of 50μL of 2% formalin in dorsal region of right posterior paw. In plantar incision group, pain was induced by plantar incision and evaluated using Von Frey filaments. Induction and maintenance of anesthesia were performed with 3% halothane for catheter placement into subarachnoid space and plantar incision. Statistical analysis was performed using the JMP® program from SAS with 5% significance level. ResultsPhentolamine at doses of 20 and 30μg increased the algesic response in the intermediate phase of the formalin test. In plantar incision test, it had hyperalgic effect on first, third, fifth, and seventh days at a dose of 10μg and on first, third, and fifth days at a dose of 20μg and on fifth day at a dose of 30μg. ConclusionSubarachnoid administration of phentolamine showed hyperalgesic effect, possibly due to the involvement of different subclasses of alpha-adrenergic receptors in modulating pain pathways.