Adult Guinea Pigs Research Articles

Feasibility of an electric current stimulator device to assess the sensory response after transversus abdominis plane block in guinea pigs (Cavia porcellus)

ObjectiveTo assess the feasibility of using an adjustable intensity nerve stimulator for evaluating the sensory response after a transversus abdominis plane (TAP) block in guinea pigs (Cavia porcellus) Study designProspective, randomized, blinded, experimental crossover study. AnimalsA total of six adult guinea pigs (Cavia porcellus). MethodsTrial A involved a unilateral TAP block with 0.5% bupivacaine (1 mL kg–1), while trial B was a unilateral sham block with an equivalent volume of 0.9% saline. In both trials, the noninjected side served as the control. An electrical stimulus was bilaterally applied at 10, 20, 30, 60, 90, and 120 minutes postinjection. Stimulus intensity was gradually increased and the current intensity (mA) at which a response (body movements and/or voluntary limb withdrawal and/or vocalization) occurred on each side was registered. Measurements over time (Friedman test) and between sides at each time point (Wilcoxon test) were compared. ResultsIn trial B, nonsignificant differences were observed between sides at each time point. In trial A, when comparing responses at each time point, nonsignificant differences were observed at 60 (p = 0.104), 90 (p = 0.598), and 120 minutes (p = 0.891); however, at 10 (p = 0.043), 20 (p = 0.027), and 30 minutes (p = 0.026), significant differences were observed. The stimulus intensity necessary to evoke a response in the bupivacaine-injected side was at least 23.8% higher than the current intensity required to elicit a response in the control side. Conclusion and clinical significanceThe electrical stimulus method appears effective in distinguishing the presence or absence of sensory blockade in guinea pigs that received a TAP block. This approach may also serve to assess the onset time and duration of the block.

Molded Round Window Niche Implant as a Dexamethasone Delivery System in a Cochlear Implant-Trauma Animal Model.

Preserving residual hearing after cochlear implant (CI) surgery remains a crucial challenge. The application of dexamethasone (DEX) has been proven to positively affect residual hearing. To deliver DEX in a localized and controlled way, a round window niche implant (RNI), allowing drug diffusion via the round window membrane into the cochlea, may be used. To prove this concept, an RNI for guinea pigs as a CI-trauma model was manufactured by molding and tested for its drug release in vitro and biological effects in vivo. The RNIs were molded using silicone containing 10% DEX. Release was analyzed over time using high-performance liquid chromatography (HPLC). Fourteen adult guinea pigs were randomly assigned to two groups (CI or CI + RNI group). All animals received a unilateral CI electrode insertion trauma followed by CI insertion. The CI + RNI group was additionally implanted with an RNI containing 10% DEX. Animals were followed up for 4 weeks. Acoustically evoked auditory brainstem response and impedance measurement, micro-computed tomography (µCT) imaging, and histology were performed for evaluation. DEX was released for more than 250 days in vitro, with an initial burst followed by a slower release over time. Comparing the hearing threshold shift (from day 0 to day 28) of the CI and CI + RNI groups, significant differences were observed at 32 and 40 kHz. The impedance shift at basal contacts was lower in the CI + RNI group than in the CI group. Moreover, the fibrosis in the lower basal turn was reduced in the CI + RNI group in contrast to the CI group. The RNI containing 10% DEX has anti-inflammatory potential concerning fibrosis inhibition and has beneficial effects on hearing preservation at high frequencies.

Effects of Red, Green and Black Pepper on Intestinal Motility and Post-Prandial Bicarbonate Concentration in Guinea Pigs

Pepper is one of the most commonly used spices in most food cultures because of its many dietary and medicinal uses. The aim of the present study was to investigate and compare the effects of different varieties of pepper on intestinal motility and post-prandial serum bicarbonate concentration in guinea pigs. The study was carried out using 50 adult guinea pigs weighing 800-1000g, separated into groups of 5 each including group 1 which served as control. The experimental groups received respectively black, green and red pepper extracts in concentrations of 25mg/kg, 50mg/kg and 75mg/kg. For each experimental group, pepper was administered together with a mixture of Evans blue dye and Arabic gum and allowed for one hour. Each animal was thereafter, anesthetized and the intestines dissected out. For each animal, the total length of the intestine as well as the distance travelled by the test meal from the pyloric sphincter were measured and recorded. Intestinal transit was expressed as the percentage of the distance travelled by the test meal to the total length of the intestine. Concomitantly, blood samples were collected to determine the post-prandial bicarbonate concentration. The result showed that all three varieties of pepper caused significant rise in percentage intestinal transit (in 1hr) and by implication reduction in the intestinal transit time. However, a significant dose-dependent effect was observed in the groups receiving black and green pepper respectively but not in the red category. This suggests an inverse relationship between the concentrations of black and green pepper with the intestinal transit time. Pepper did not cause any significant change in the plasma post-prandial bicarbonate concentrations. Conclusively, the results suggest that black, green and red pepper respectively increased intestinal motility without possibly causing any significant effect on gastric acid secretion.

Histomorphological and Histochemical Study of Esophagus and Stomach in Adult Guinea Pigs (Cavia porcellus)

This study was performed to examine and compare the esophagus and stomach histomorphological and histochemical characteristics during adulthood to clarify micromorphological alterations. In addition to the importance of this animal species as a model in many scientific experiments and due to some of its unique anatomical and physiological features. It also supports further studies on vital processes of the digestive system, such as food processing and absorption. To conduct such a project, ten heathy adult guinea pigs at 2 months age and weighing 461.8±8.3g were gathered from the public spinning market. The animals were euthanized and dissected, then the organs were topographically investigated in situ, and samples were collected from the ten animals and was kept in 10% neutral buffered formalin for routine histological procedures. The esophagus is a musculo – membranous tube structure extended from the pharynx to the stomach, measured about 10.54±0.14 cm in length and 0.35±0.01 g in weight, and segmented according to its position in the body into three sections: the cervical, thoracic, and abdominal. The stomach is a simple unilocular transverse grayish white sac-like structure of the digestive system; it connects the esophagus to the intestine; its mean length was 4.39±0.11 cm; its capacity was 17.01±0.22 ml; and its weight was 7.07±0.05 gm. It lacks an outward demarcation-limiting ridge between its divisions and appears relatively smooth. Histologically, the esophagus is devoid of glands, while the stomach's three interior sections are dotted with glands, and both organs consist of the same four basic histological layers.

Electroanatomical adaptations in the guinea pig heart from neonatal to adulthood.

Electroanatomical adaptations during the neonatal to adult phase have not been comprehensively studied in preclinical animal models. To explore the impact of age as a biological variable on cardiac electrophysiology, we employed neonatal and adult guinea pigs, which are a recognized animal model for developmental research. Electrocardiogram recordings were collected in vivo from anaesthetized animals. A Langendorff-perfusion system was employed for the optical assessment of action potentials and calcium transients. Optical data sets were analysed using Kairosight 3.0 software. The allometric relationship between heart weight and body weight diminishes with age, it is strongest at the neonatal stage (R2 = 0.84) and abolished in older adults (R2 = 1E-06). Neonatal hearts exhibit circular activation, while adults show prototypical elliptical shapes. Neonatal conduction velocity (40.6 ± 4.0 cm/s) is slower than adults (younger: 61.6 ± 9.3 cm/s; older: 53.6 ± 9.2 cm/s). Neonatal hearts have a longer action potential duration (APD) and exhibit regional heterogeneity (left apex; APD30: 68.6 ± 5.6 ms, left basal; APD30: 62.8 ± 3.6), which was absent in adults. With dynamic pacing, neonatal hearts exhibit a flatter APD restitution slope (APD70: 0.29 ± 0.04) compared with older adults (0.49 ± 0.04). Similar restitution characteristics are observed with extrasystolic pacing, with a flatter slope in neonates (APD70: 0.54 ± 0.1) compared with adults (younger: 0.85 ± 0.4; older: 0.95 ± 0.7). Neonatal hearts display unidirectional excitation-contraction coupling, while adults exhibit bidirectionality. Postnatal development is characterized by transient changes in electroanatomical properties. Age-specific patterns can influence cardiac physiology, pathology, and therapies for cardiovascular diseases. Understanding heart development is crucial to evaluating therapeutic eligibility, safety, and efficacy.

Development and validation of a pain scale in guinea pig (Cavia porcellus)

BackgroundThis study aimed to develop and validate a pain assessment scale for guinea pigs to be performed in clinics by veterinarians. The scale was established using pre-existing pain scales from other species and was based on signs expressed by guinea pigs in pain already identified in the literature. The scale consists of 14 descriptors grouped into four categories: appearance, functional, physiological and behavioral. Each item on the scale was assigned a score based on the observation and handling of the animals. The total score obtained ranged from 0 to 26, with more intense pain scoring higher. MethodsFifty-eight adult guinea pigs presenting at the authors' Teaching Hospital between March 2021 and November 2022 were assessed. Guinea pigs were filmed during their consultation and an information sheet was completed. The information sheet provided details on the animals' appetite, fecal production, and behavior at home. The videos and corresponding information sheets were then reviewed to attribute a pain score to each animal. The pain scores were measured twice by a same observer one month apart to assess repeatability and by a second observer to assess reproducibility. The validity was assessed by correlating the pain scores given by the novel scale with scores using a numerical rating scale (NRS) as a gold standard method. ResultsThe initial Cronbach's alpha obtained was 0.77, which was satisfactory. However, it highlighted that items concerning pruritus and spasmodic movements should be deleted to strengthen internal consistency. Then, Lin's coefficient and Bland and Altman's graphical method highlighted that the scale had an almost strong repeatability and intra-operator reproducibility. Moreover, the correlation between pain intensities obtained with the novel scale and the scores given using NRS was correct (Kappa = 0.72). The specificity was 87.5%, but the sensitivity of the scale was 52.0%. Each item's repeatability and reproducibility were assessed to identify items that would benefit from added clarification. ConclusionOur work is the first step in establishing a pain scale in guinea pigs. However, it should not yet be used in a clinical context. Indeed, the scale was not good at detecting pain when a guinea pig was actually painful. Further studies, including improvement of certain items and testing a larger sample of animals, are ongoing.

The entrainment of action potential duration and contraction amplitude by recapitulation of respiratory sinus arrhythmia in isolated cardiac myocytes

Abstract Introduction Respiratory sinus arrhythmia (RSA) is the oscillation of heart rate in phase with ventilation and represents the high frequency component of heart rate variability. RSA is prevalent in the young and the endurance-trained and its loss is considered a prognostic indicator for sudden cardiac death. The recapitulation of RSA improves cardiac function in animal models of heart failure1,2. However, the precise mechanisms by which RSA affects cardiac function are unknown. Hypothesis: We examined the hypothesis that the recapitulation of RSA in isolated ventricular myocytes affects the stimulus interval-dependence of action potential duration (APD) and sarcomere shortening through mechanisms involving sarcoplasmic reticulum (SR) Ca2+ release. Methods Hearts were excised from adult male guinea pigs under general anaesthesia (140 mg/kg bodyweight euthatal, i.p.) and left ventricular myocytes isolated. Isolated myocytes were superfused with Tyrode’s solution for perforated patch whole-cell current clamp recording and action potentials and sarcomere length measured simultaneously. Sample sizes are presented as n/N (cell/animal number) and nested hierarchical analysis applied using a generalized linear mixed model (P<0.05). Results Pacing at a basic cycle length (CL, 350 ms) induced APD, Ca2+ transient amplitude (CaT) and sarcomere shortening alternans. The recapitulation of RSA through oscillatory pacing (OP), in which CL was set to 20% below and 20% above the corresponding basic CL in a 2-short, 2-long stimulus train, reduced the incidence of alternans. Furthermore, OP entrained APD, CaT and sarcomere shortening and this entrainment persisted in voltage clamp experiments with fixed APD. Using a three-step protocol to examine the dependence of APD and sarcomere shortening on both preceding (CLn-1) and anteceding (CLn-2) stimulus intervals, both APD and sarcomere shortening were found to depend directly on the preceding cycle length (CLn-1, P<0.001). In contrast, sarcomere shortening depended inversely on the anteceding CL (CLn-2, P<0.001; n/N = 24/4). Following treatment of the cells with caffeine (50 µM) to sensitise ryanodine receptors, the dependence of APD and sarcomere shortening on CLn-1 was markedly suppressed, and the inverse dependence of sarcomere shortening on CLn-2 was lost (P<0.001, n/N = 6/3). The effects of OP are akin to post-extrasystolic potentiation3 and mathematical simulation4 supports the involvement of changes in the sarcoplasmic reticulum Ca2+ content. Conclusion These data are consistent with an obligatory role for the SR in the entrainment of APD, CaT and sarcomere shortening and the suppression of alternans by the recapitulation of RSA. We hypothesise that recapitulation of RSA would be protective against ventricular tachyarrhythmia and further work is required to test this.

The Nutritional Value of Biowaste Bovine Slaughterhouse Meals for Monogastric Species Feeding: The Guinea Pig as an Animal Model.

Biowaste from slaughterhouses can be recovered to benefit food security and reduce contamination potential. More than 3 billion heads of livestock are consumed worldwide, which will increase by 17% by 2028, generating more biowaste, increasing infectious agents, and causing economic losses due to circular economy principles not being applied. This work evaluated the nutritional quality of four types of biowaste from bovine slaughter which were transformed into a meal for guinea pigs (rumen content (RCM), ears (EaM), blood (BM), and cheeks (CM)) according to their chemical composition, digestible components, energy contribution, and voluntary consumption. For the animal model, adult male guinea pigs were arranged in metabolic cages for feces collection without urinary contamination. Nine guinea pigs were used in each digestibility test. First, a direct digestibility test was conducted using a meal of barley as a reference diet (RD), the indigestibility coefficient of which allowed for the estimation of the digestibility of biowaste meals through indirect calculations; for this, diets composed of 80% of the RD and 20% of the corresponding biowaste meals were evaluated. The difference method was suitable for determining the digestibility of beef biowaste using the indigestibility coefficients of the reference diet to calculate the digestibility of ingredients which could not be offered as 100% of the meal but were incorporated as 20%. The digestible protein and metabolizable energy contents of RCM, EaM, BM, and CM were 10.2% and 2853 kcal/kg, 44.5% and 3325 kcal/kg, 70.7% and 2583 kcal/kg, and 80.8% and 3386 kcal/kg, respectively. The CM and BM feeds had the highest contributions of digestible protein due to their higher nitrogen content, and the CM and EaM feeds had the highest ME contents due to their higher fat contents. The biowaste meal consumption in descending order was CM > RCM > EaM > BM, which were consumed without problems. These results are indicative that these components can be part of guinea pigs' diets, and it is recommended to continue studies into guinea pig growth and fattening diets with different levels of these biowaste meals.

Probiotic capacity of commensal lactic acid bacteria from the intestine of Guinea pigs (Cavia porcellus)

The intricate balance of intestinal microbiota is significantly influenced by the pivotal role of indigenous lactic acid bacteria (LAB). These LAB not only contribute to antimicrobial activity and enhance animal health and productivity but also serve as defense against intestinal infections. In the present study, the probiotic potential of LAB strains isolated from various intestinal sections of adult and young guinea pigs (Cavia porcellus) was comprehensively assessed. Strains belonging to the genera Ligilactobacillus, Weissella, Enterococcus, and Limosilactobacillus were also identified. The antibacterial activities of the LAB strains against Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus were quantified. Exopolysaccharide production, adherence capacity, antibiotic resistance, and bile salt tolerance (0.15 %, 0.30 %, and 0.45 %) of LAB were quantified. Further analyses focused on the effects of pH (2.9, 5.0, 6.4, and 7.4), temperature (40, 50, and 60 °C) and NaCl concentrations (3.5 % and 6.5 % w/v) on LAB growth. Strains GCI9 and GDE10 (Ligilactobacillus salivarius), isolated from the cecum and intestine of guinea pigs, exhibited significant antimicrobial activity against S. typhimurium, E. coli and S. aureus. Remarkable adherence capacity to porcine gastric mucin was demonstrated by L. salivarius strains, specifically ACI1, GCI9, and GDE10, with the highest exopolysaccharide levels produced by ACI1 and GCI9 (1.71 and 1.76 mg/mL, respectively). The probiotic potential was further underscored by remarkable bile salt tolerance, especially in strain GDE10, and substantial exopolysaccharide production. These strains displayed notable adaptability to varying environmental conditions, including NaCl concentrations at 3.5 % and 6.5 %, temperatures ranging from 40 to 60 °C, and pH levels of 2.9, 5.0, 6.4, and 7.4. This comprehensive assessment of the probiotic properties of L. salivarius strains, particularly ACI1, GCI9, and GDE10, shows promise for the development of probiotic formulations aimed at enhancing the intestinal health of guinea pigs.

Establishing New Isosexual Pairs in Adult Male Guinea Pigs (Cavia porcellus) to Facilitate Social Housing.

Guinea pigs (Cavia porcellus) are a commonly used species in biomedical research. As social creatures, compatible guinea pigs should be housed together unless scientific objectives or veterinary care require otherwise. Extensive literature suggests that adult male guinea pigs are highly aggressive in the presence of females, but data are lacking regarding the compatibility of cohoused adult males in the absence of females. Most studies that use adult males do not report housing densities. We used serial wound scoring and observations of behavior to determine whether unfamiliar adult male guinea pigs will develop stable, prosocial isosexual pairs. Wound scoring was performed before and 24 h after pairing. Serial behavioral observations assessed affiliative and agonistic behaviors at 0.5, 2, 24, and 48 h after pairing. Wound scoring and behavioral observations continued weekly for 1 mo and monthly thereafter. Wound scores were significantly higher at 24 h after pairing as compared with baseline and all other time points. Wounding was rare after week 2, indicating reduced aggression. Furthermore, affiliative behaviors significantly increased over time while agonistic behaviors were rare. Together, these data suggest that unfamiliar adult male guinea pigs establish stable prosocial pairs after an acclimation period. As was done in the present study, providing ample space, separate shelters for each animal, and the absence of female guinea pigs will likely facilitate successful pairing. We recommend consideration of a social housing program for adult male guinea pigs to provide companionship and enrich their housing environment.

Mice, rats, and guinea pigs differ in FMOs expression and tissue concentration of TMAO, a gut bacteria-derived biomarker of cardiovascular and metabolic diseases.

Increased plasma trimethylamine oxide (TMAO) is observed in cardiovascular and metabolic diseases, originating from the gut microbiota product, trimethylamine (TMA), via flavin-containing monooxygenases (FMOs)-dependent oxidation. Numerous studies have investigated the association between plasma TMAO and various pathologies, yet limited knowledge exists regarding tissue concentrations of TMAO, TMAO precursors, and interspecies variability. Chromatography coupled with mass spectrometry was employed to evaluate tissue concentrations of TMAO and its precursors in adult male mice, rats, and guinea pigs. FMO mRNA and protein levels were assessed through PCR and Western blot, respectively. Plasma TMAO levels were similar among the studied species. However, significant differences in tissue concentrations of TMAO were observed between mice, rats, and guinea pigs. The rat renal medulla exhibited the highest TMAO concentration, while the lowest was found in the mouse liver. Mice demonstrated significantly higher plasma TMA concentrations compared to rats and guinea pigs, with the highest TMA concentration found in the mouse renal medulla and the lowest in the rat lungs. FMO5 exhibited the highest expression in mouse liver, while FMO3 was highly expressed in rats. Guinea pigs displayed low expression of FMOs in this tissue. Despite similar plasma TMAO levels, mice, rats, and guinea pigs exhibited significant differences in tissue concentrations of TMA, TMAO, and FMO expression. These interspecies variations should be considered in the design and interpretation of experimental studies. Furthermore, these findings may suggest a diverse importance of the TMAO pathway in the physiology of the evaluated species.

Tripolar configuration and pulse shape in cochlear implants reduce channel interactions in the temporal domain

The present study investigates effects of current focusing and pulse shape on threshold, dynamic range, spread of excitation and channel interaction in the time domain using cochlear implant stimulation. The study was performed on 20 adult guinea pigs using a 6-channel animal cochlear implant, recording was performed in the auditory midbrain using a multielectrode array. After determining the best frequencies for individual recording contacts with acoustic stimulation, the ear was deafened and a cochlear implant was inserted into the cochlea. The position of the implant was controlled by x-ray. Stimulation with biphasic, pseudomonophasic and monophasic stimuli was performed with monopolar, monopolar with common ground, bipolar and tripolar configuration in two sets of experiments, allowing comparison of the effects of the different stimulation strategies on threshold, dynamic range, spread of excitation and channel interaction. Channel interaction was studied in the temporal domain, where two electrodes were activated with pulse trains and phase locking to these pulse trains in the midbrain was quantified. The results documented multifactorial influences on the response properties, with significant interaction between factors. Thresholds increased with increasing current focusing, but decreased with pseudomonophasic and monophasic pulse shapes. The results documented that current focusing, particularly tripolar configuration, effectively reduces channel interaction, but that also pseudomonophasic and monophasic stimulation and phase duration intensity coding reduce channel interactions.

Ultrastructural Architecture Studies of Pancreas in Guinea pig

Background: The pancreas is an accessory organ of the digestive system and also an important endocrine organ of vertebrates that produce and release substances in the body. The pancreas has both endocrine and exocrine function. Its endocrine function is to regulate blood sugar levels by secretion of hormones like insulin, glucagon, stomatostatin and pancreatic polypeptide and an exocrine function that helps in digestion. The study was performed to document the ultrastructural details of pancreas of guinea pigs by scanning and transmission electron microscopy. Methods: Six adult healthy guinea pigs of 16-32 weeks of age (Irrespective of sex) were procured from the Department of Laboratory Animal Medicine, TANUVAS as per ethical committee approval. Animals were dissected according to standard operating procedure by using the Carbon dioxide asphyxiations as per CPCSEA norms and pancreatic pieces were utilised for SEM and TEM study. Result: Pancreas was irregular in shaped and showed splenic, ventricular and intestinal lobes. In SEM, the parenchyma was covered by the dense irregular capsule. Each lobule contained many acini which were connected by a thin, long duct with branched pattern arrangement with increasing wall thickness and diameter. In TEM, the pancreatic tissue consisted of glandular lobules comprised of acini, islets of Langerhans and connective tissue between the lobules. Numerous mitochondria and golgi complexes were also present in the acinar cell cytoplasm along with zymogen granules and rough endoplasmic reticulum. The centroacinar cells were also found. A special type of interstitial cell named telocytes and each was found with many telopodes in the exocrine part of pancreatic parenchyma. Among the four islet cell types, alpha and beta cells could be identified.

Investigation of a maxillary nerve block technique in guinea pigs (Cavia porcellus): A cadaveric study comparing two injectate volumes

ObjectiveTo investigate and describe an extraoral approach to perform a maxillary nerve block in guinea pigs. Study designProspective, randomized, blinded, descriptive, cadaveric study. AnimalsA total of 14 adult guinea pig cadavers. MethodsTwo cadavers were used for anatomic dissection and determination of maxillary nerve block approach. A maxillary nerve block via infraorbital approach was then performed in 12 cadavers. A low volume (0.1 mL) or high volume (0.2 mL) of diluted methylene blue injectate was randomly assigned to the right or left side, with the other volume used for the contralateral side. The maxillary nerve was dissected after each injection by an investigator blinded to injectate volume. The region of dye distribution was identified, and the degree of staining assigned an accuracy score (0–2). Nerve coverage was considered adequate if ≥6 mm of circumferential staining was present. ResultsAccuracy evaluation indicated successful dye deposition in 10/12 [2 (0–2), median (range)] injections in the low volume group and 8/12 [2 (1–2)] injections in the high volume group. The majority (79.2%) of injections resulted in adequate nerve staining. There were no statistically significant differences between injectate volumes for accuracy (p = 0.64) or adequacy (p > 0.99) of staining. ConclusionsThe infraorbital approach is a simple and practical method for maxillary nerve blockade in guinea pigs. An injectate volume of 0.1 mL results in adequate maxillary nerve coverage; however, additional studies are needed to assess the efficacy in clinical use.

Neural and behavioral binaural hearing impairment and its recovery following noise-induced cochlear synaptopathy

Noise-induced cochlear synaptopathy refers to a loss of synapses in the inner ear but no change in audiometric thresholds. Animal studies have focused primarily on peripheral hearing measures to diagnose synapse loss, while suggesting binaural listening deficits such as speech-reception-in-noise result from this disorder, but have not accounted for the possible regeneration of synapses. To address this, we measured binaural physiological and behavioral function in adult guinea pigs with noise-induced synaptopathy. Physiological measurements extended to two months post noise exposure. While common audiological assessments showed temporary threshold loss, reduced evoked potential amplitudes indicative of synaptopathy and measurable binaural electrophysiological hearing deficits post exposure, all measures recovered by two months including binaural behavior. Suspected regeneration of synaptic ribbons occurred by two months post exposure and cochlear histology revealed no synaptic loss two months post exposure. We show that the same noise exposure protocol that caused synaptic loss in prior studies causes physiological binaural processing deficits in the brainstem and that the regeneration of synapses corresponds with recovered binaural processing including behavior. Results suggest that functional recovery of ribbon synapses post a single moderate noise exposure is sufficient to restore binaural hearing abilities.

Prokaryotic voltage-gated sodium channels are more effective than endogenous Nav1.5 channels in rescuing cardiac action potential conduction: an in silico study.

Methods to augment Na+ current in cardiomyocytes hold potential for the treatment of various cardiac arrhythmias involving conduction slowing. Because the gene coding cardiac Na+ channel (Nav1.5) is too large to fit in a single adeno-associated virus (AAV) vector, new gene therapies are being developed to enhance endogenous Nav1.5 current (by overexpression of chaperon molecules or use of multiple AAV vectors) or to exogenously introduce prokaryotic voltage-gated Na+ channels (BacNav) whose gene size is significantly smaller than that of the Nav1.5. In this study, based on experimental measurements in heterologous expression systems, we developed an improved computational model of the BacNav channel, NavSheP D60A. We then compared in silico how NavSheP D60A expression vs. Nav1.5 augmentation affects the electrophysiology of cardiac tissue. We found that the incorporation of BacNav channels in both adult guinea pig and human cardiomyocyte models increased their excitability and reduced action potential duration. When compared with equivalent augmentation of Nav1.5 current in simulated settings of reduced tissue excitability, the addition of the BacNav current was superior in improving the safety of conduction under conditions of current source-load mismatch, reducing the vulnerability to unidirectional conduction block during premature pacing, preventing the instability and breakup of spiral waves, and normalizing the conduction and ECG in Brugada syndrome tissues with mutated Nav1.5. Overall, our studies show that compared with a potential enhancement of the endogenous Nav1.5 current, expression of the BacNav channels with their slower inactivation kinetics can provide greater anti-arrhythmic benefits in hearts with compromised action potential conduction.NEW & NOTEWORTHY Slow action potential conduction is a common cause of various cardiac arrhythmias; yet, current pharmacotherapies cannot augment cardiac conduction. This in silico study compared the efficacy of recently proposed antiarrhythmic gene therapy approaches that increase peak sodium current in cardiomyocytes. When compared with the augmentation of endogenous sodium current, expression of slower-inactivating bacterial sodium channels was superior in preventing conduction block and arrhythmia induction. These results further the promise of antiarrhythmic gene therapies targeting sodium channels.

Transfer RNA-mediated restoration of potassium current and electrical correction in premature termination long-QT syndrome hERG mutants

Disease-causing premature termination codons (PTCs) individually disrupt the functional expression of hundreds of genes and represent a pernicious clinical challenge. In the heart, loss-of-function mutations in the hERG potassium channel account for approximately 30% of long-QT syndrome arrhythmia, a lethal cardiac disorder with limited treatment options. Premature termination of ribosomal translation produces a truncated and, for potassium channels, a potentially dominant-negative protein that impairs the functional assembly of the wild-type homotetrameric hERG channel complex. We used high-throughput flow cytometry and patch-clamp electrophysiology to assess the trafficking and voltage-dependent activity of hERG channels carrying patient PTC variants that have been corrected by anticodon engineered tRNA. Adenoviral-mediated expression of mutant hERG channels in cultured adult guinea pig cardiomyocytes prolonged action potential durations, and this deleterious effect was corrected upon adenoviral delivery of a human ArgUGA tRNA to restore full-length hERG protein. The results demonstrate mutation-specific, context-agnostic PTC correction and elevate the therapeutic potential of this approach for rare genetic diseases caused by stop codons.

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (μCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using μCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by μCT, before and after contrast staining with osmium tetroxide (OsO4), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that μCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO4 significantly enhanced the visible tissue reaction detected using μCT. Overall, μCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.

Egg Yolk-Supplemented Tris-Citric Acid Extender Improves the Prefreezing and Post-Thaw Sperm Quality Indices of Guinea Pig (Cavia porcellus) Epididymal Spermatozoa.

This study aimed to assess the suitability of egg yolk (EY) supplementation to a tris-citric acid-based extender on cryosurvival of guinea pig (Cavia porcellus) epididymal spermatozoa. Two synthetic-based extenders, tris-citric acid-glucose plus 20% EY (TCG-EY) and tris-citric acid-fructose (TCF) both with 5% glycerol, were compared. Thirty-two epididymides were recovered from 16 adult guinea pig males by gonadectomy, and then the sperm samples were retrieved by retrograde flushing using TCG-EY and TCF extenders for left or right epididymis, respectively. TCG-EY and TCF sperm samples were frozen in static liquid nitrogen vapors through a two-step cooling procedure. Before freezing, the percentage of progressive sperm motility and sperm with intact plasma and acrosome membranes from TCG-EY sperm samples were higher (p < 0.05) than those diluted with TCF. Post-thaw sperm kinematic variables and membrane integrity were drastically reduced (p < 0.001) compared with prefreezing samples, regardless of extender type. The post-thaw plasmatic and acrosome membrane integrity from TCG-EY sperm samples was higher (p < 0.05) than those from TCF samples. Except for the length, the morphometric head dimensions of sperm diluted with TCG-EY or TCF did not vary (p > 0.05) after the freezing-thawing process compared with the prefreezing samples. In conclusion, despite greater cell cryoinjury with both extenders, the EY supplementation exerted greater cell membrane protection before and after the freezing-thawing process. This research shows an in-depth analysis of guinea pig sperm cryopreservation; however, more studies are recommended.

Evaluation of Hepatoprotective Efficacy of a Polyherbal Unani Formulation Majoon-Najah against Cadmium Chloride-induced Liver Damage.

Majoon-Najah is a composite Unani formulation that consists of multiple medicinal plants and is advised for neurological illnesses. Several studies were carried out on Majoon-Najah (MN) and its ingredients to evaluate the protective effect against seizure and antidepressant activity in animals using a classical form as well as extract. Terminalia bellerica and Emblica officinalis are the major constituents of MN. Scientifically documented literature summarises the hepatoprotective potential of these constituents. The current study aimed to evaluate the possible hepatoprotective, antioxidant and antiinflammatory perspective of traditional Indian Unani formulation MN and Majoon-Najah hydroalcoholic extract (MNHE) in a Guinea pig model. Thirty adult male albino guinea pigs were randomly assigned into five groups for this study. MN and MNHE were given intragastrically for 15 days, followed by intraperitoneal Cadmium chloride (CdCl2, 3 mg/kg/day) from days 8 to 15, as per the schedule. Blood samples were taken from the heart on the 16th day, and the liver was operated on for biochemical analysis and histopathology under complete anesthesia. CdCl2 changed the levels of liver function markers, serum biochemical indicators like albumin, total protein, glucose, and cholesterol in the blood; lipid peroxidation (MDA), glutathione reductase (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in hepatic tissue homogenate, pro-inflammatory cytokines level and liver cytoarchitecture. MN and MNHE were found to protect guinea pigs' liver from CdCl2-induced injury by lowering raised parameters and increasing enzymatic antioxidants. MN and MNHE did not significantly heal injured liver tissues caused by CdCl2 in histopathological examinations. CdCl2 induces hepatotoxicity that is likely to worsen with increasing dosage and duration of exposure. MN and MNHE exert their hepatoprotective action by scavenging free radicals, decreasing malondialdehyde levels, activating antioxidant enzymes, and down-regulating proinflammatory indicators.