Potential In Rats Research Articles

Motor-evoked potentials after focal electrical stimulation predict drug-induced convulsion potentials in rats

Drug-induced convulsions—often caused by the inhibition of GABA receptors and stimulation of glutamate receptors—are difficult to predict in animals. In this study, we attempted to detect the proconvulsant potential using motor-evoked potentials (MEPs) after focal electrical stimulation or upon using a functional observational battery (FOB). Pentylenetetrazole, kainic acid, and pilocarpine were used as convulsion-inducing drugs, and baclofen was used as a negative control. First, each compound was administered to male rats, and the FOB tests were performed. All drugs induced behavioral changes, but no commonality was found. Single electrical stimulation train MEPs were recorded under anesthesia for 60 min (at 5 min intervals) after administration of each drug. A dose-dependent increase in MEPs was observed for each convulsion-inducing drug. Moreover, paired electrical stimulation (conditioned and test) of the cerebral motor cortex was conducted with a 1–15 ms interstimulus interval (ISI), 10 min after administration of the drug. All convulsion-inducing drugs inhibited the short-interval intracortical inhibition (ISI: 3 ms), which may be associated with GABA. Intracortical facilitation (ISI: 11 ms), related to glutamate, was not enhanced by any drug but was inhibited by pilocarpine. Dose correlation was not found in short-interval intracortical inhibition or intracortical facilitation in any drugs. No changes in MEPs were observed after baclofen administration. These results suggest that it is possible to evaluate the convulsion potential and associated mechanisms using MEP, independent of the behavioral changes. The early identification of convulsion potential using this model will lead to more efficient drug development.

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

ObjectivesRats are commonly used for translational pain and spinal cord stimulation (SCS) research. Although many SCS parameters are configured identically between rats and humans, stimulation amplitudes in rats are often programmed relative to visual motor threshold (vMT). Alternatively, amplitudes may be programmed relative to evoked compound action potential (ECAP) thresholds (ECAPTs), a sensed measure of neural activation. The objective of this study was to characterize ECAPTs, evoked compound muscle action potential thresholds (ECMAPTs), and vMTs with clinically relevant SCS modalities. Materials and MethodsWe implanted ten anesthetized rats with two quadripolar epidural SCS leads: one for stimulating in the lumbar spine, and another for sensing ECAPs in the thoracic spine. We then delivered two SCS paradigms to the rats. The first used 50-Hz SCS with 50-, 100-, 150-, and 200-μs pulse widths (PWs), whereas the second used a 50-Hz, 150-μs PW low-rate program (LRP) multiplexed to a 1200-Hz, 50-μs PW high-rate program (HRP). We increased SCS amplitudes up to the vMT in the first paradigm, and in the second, we increased HRP amplitudes up to the HRP ECAPT with a fixed amplitude (70% of the vMT) LRP. For each test case, we captured ECAPTs, ECMAPTs, and vMTs from each rat. ResultsvMTs were 3.0 ± 0.7 times greater than ECAPTs, with vMTs marginally (3.0 ± 3.6%) greater than ECMAPTs (mean ± SD) across all PWs with the first paradigm. With the second paradigm, we noted a negligible increase (3.6 ± 6.2%) on the LRP ECAP as HRP amplitudes were increased. ConclusionsOur results demonstrate reasonable levels of neural activation in anesthetized rats with SCS amplitudes appropriately programmed relative to vMT or ECMAPT when using clinically relevant SCS modalities. Furthermore, we demonstrate the feasibility of ECAP recording in rats with multiplexed HRP SCS.

Novel Isoxazole Derivative Attenuates Ethanol-Induced Gastric Mucosal Injury through Inhibition of H+/K+-ATPase Pump, Oxidative Stress and Inflammatory Pathways.

Isoxazole derivatives are significant enough due to their wide range of pharmacological and therapeutic activities. The purpose of the current study is to use computational, in vitro, in vivo, and extensive molecular approaches to examine the possible anti-ulcer activity of 4-benzylidene-3 methyl-1,2-isoxazol-5(4H)-one (MBO). Biovia Discovery Studio visualizer (DSV) was utilized for virtual screening. A tissue antioxidant investigation, H+/K+-ATPase test, and anti-H. pylori activities were carried out. ELISA, immunohistochemistry, and PCR methods were employed for the proteome analysis. An ethanol-induced stomach ulcer model was used to examine the anti-ulcer potential in rats. The binding affinities for MBO ranged from −5.4 to −8.2 Kcal/mol. In vitro findings revealed inhibitory activity against H. pylori and the H+/K+-ATPase pump. It also enhanced levels of glutathione, catalase, and glutathione-S-transferase and reduced lipid peroxidation levels in gastric tissues of rats. In vivo results showed the gastro-protective effect of MBO (30 mg/kg) in ulcerative rat stomachs. The proteomic study revealed decreased expression of inflammatory markers (cyclooxygenase-2, p-NFkB, and TNF-α). In RT-PCR analysis, the expression levels of H+/K+-ATPase were reduced. Furthermore, ADMET (absorption, distribution, metabolism, excretion and toxicity) studies revealed that MBO has high GIT solubility and has a safer profile for cardiac toxicity. This study suggests that MBO displayed anti-ulcer potential, which may have been mediated through the inhibition of the H+/K+-ATPase pump, as well as antioxidant and anti-inflammatory pathways. It has the potential to be a lead molecule in the treatment of peptic ulcers with fewer adverse effects.

A Temporal–Spatial Atlas of Peripheral Nerve Evoked Cortex Potential in Rat: A Novel Testbed to Explore the Responding Patterns of the Brain to Peripheral Nerves

Observing the dynamic progress of the brain in response to peripheral nerve stimulation as a whole is the basis for a deeper understanding of overall brain function; however, it remains a great challenge. In this work, a novel mini-invasive orthogonal recording method is developed to observe the overall evoked cortex potential (ECP) in rat brain. A typical ECP atlas with recognizable waveforms in the rat cortex corresponding to the median, ulnar, and radial nerve trunks and subdivided branches is acquired. Reproducible exciting temporal–spatial progress in the rat brain is obtained and visualized for the first time. Changes in the ECPs and exciting sequences in the cortex four months after median nerve transection are also observed. The results suggest that the brain’s response to peripheral stimulation has precise and reproducible temporal–spatial properties. This resource can serve as a testbed to explore the overall functional interaction and dynamic remodeling mechanisms between the peripheral and central nervous systems over time.

Experimental evaluation of an antimicrobial protein from Bacillus amyloliquefaciens MBL27 for wound healing potential in rats

Experimental evaluation of an antimicrobial protein from Bacillus amyloliquefaciens MBL27 for wound healing potential in rats

Effects of the Oral Administration of Aqueous and Methanolic Leaf Extracts of Chenopodium ambrosioides L. (Amaranthaceae) on Blood Glucose Levels in Wistar Rats.

BackgroundDiabetes mellitus is a metabolic disorder that poses a major global health threat. The current diabetes mellitus uses insulin and oral hypoglycemic agents, which have limitations, including adverse effects and secondary failures. Herbal medicine is being evaluated for its role in the pharmacotherapy of diabetes. This study was aimed to assess the anti-diabetic potential and short-term toxicity level of Chenopodium ambrosioides collected from Bukavu in Democratic Republic of Congo.MethodsLeaves of C. ambrosioides were extracted by infusion and maceration with distilled water and 95% methanol, respectively. Hypoglycemic and antihyperglycemic potentials of the aqueous and methanolic were investigated in normoglycemic and intraperitoneal glucose-loaded rats at 100, 200, and 400 mg/kg body weight. An oral acute toxicity test was carried out on healthy female Wistar rats.ResultsAcute toxicity test showed the mean lethal dose (LD50) for both aqueous and methanol extracts of C. ambrosioides to be more than 2000 mg/kg. The group treated with glibenclamide (5 mg/kg b.w) and aqueous extract of the plant (200 mg/kg b.w) showed a significant reduction (p< 0.0001 and p< 0.05) of fasting blood glucose by 46.91% and 16.72%, respectively, compared to control and all other treatment groups. In acute conditions, a single oral administration of the aqueous and methanolic extracts lowered fasting blood glucose in rats. Any manifestation and signs of toxicity and mortality have been recorded for 14 days of observation.ConclusionLeaf aqueous and methanolic extracts of C. ambrosioides appeared safe at 2000 mg/kg. The plant demonstrated some anti-diabetic potential in rats, explaining its use as an anti-diabetic remedy locally.

Investigations on Ipomoea reniformis seeds for antiulcer potential in rats

Investigations on Ipomoea reniformis seeds for antiulcer potential in rats

Phytochemical characterization, antihyperglycaemic and antihyperlipidemic activities of Setaria megaphylla in alloxan-induced diabetic rats

BackgroundSetaria megaphylla (Steud) Dur & Schinz (Poaceae), a grass used ethnomedically by herbalists in Nigeria for the treatment of diabetes was evaluated for antidiabetic, hypolipidemic and pancreas protective potentials in rats. MethodsSolvents fractions (hexane, dichloromethane (DCM), ethyl acetate (EA) and methanol ) were investigated for antidiabetic, hypolipidemic and pancreas protective potentials in alloxan-induced diabetic rats. Glibenclamide was used as positive control. The fasting blood glucose (FBG) level, serum insulin, glycosylated hemoglobin (Hb1Ac), oral glucose tolerance test (OGTT) and lipids levels were determined. Histopathological study of the pancreas was done. Isolation of phytochemicals and their subsequent identification using Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy were carried out. ResultsTreatment of alloxan-induced diabetic rats with the leaf fractions caused significant (p < 0.05–0.001) reduction in FBG of treated diabetic rats in acute and prolonged studies as well as OGTT with DCM, EA and hexane fractions having pronounced activities. The leaf fractions also caused significant (p < 0.01) decreases in Hb1Ac levels and increases in serum insulin levels. The leaf fractions further caused lowering of serum total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL) with increased high density lipoprotein (HDL) level in the treated diabetic rats. Histopathological study of pancreas revealed protective effect by the leaf fractions. 1-Triacontanal, 1-triacontanol, 1-dotriacontanol, 1-triacontyl cerotate, and stigmasterol were isolated and identified from the active DCM and EA fractions of this plant for the first time . ConclusionThe leaf fractions of S.megaphylla possess hypoglycemic, insulin secretion stimulatory, hypolipidemic, and pancreas protective potentials which may be due to the activities of the phytochemical constituents.

The effect of canakinumab on COVID19-associated cardiomyocyte contractile dysfunction and arrhythmias

Abstract Background Cardiac injury associated with cytokine release occurs in almost 20% of SARS-CoV-2 positive patients during hospitalization and mortality is particularly high in these patients. Cardiac enzyme (e.g. troponin or creatinine kinase (CK)) elevations are a frequently reported finding, indicating myocardial damage and arrhythmias are the cause for ICU transfer in up to 12% of patients. However, the mechanistic role of COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. In addition, the role of anti-inflammatory therapy approaches to mitigate this cardiac dysfunction remains elusive. Methods We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPSc-CM). Moreover, we evaluated the therapeutic potential of the IL1-beta antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. Results Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 plasma from intensive care unit patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Cardiomyocytes showed decreased Ca2+ transient amplitudes and altered baseline Ca2+ concentrations leading to impaired cellular contractile function upon electrical field-stimulation and exposure to patient plasma (n=276 control and 359 COVID19 cells; Fura). In addition, we used iPSc-CM to explore the long-term effect of patient plasma on cardiac electrical and mechanical function in a translational setting (24h incubation; Fluo). In iPSc, spontaneous Ca2+ release events (i.e. Ca2+ waves and Ca2+ sparks) were more likely to occur upon incubation with COVID19 plasma and nuclear as well as cytosolic Ca2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca2+ release or Ca2+ signaling during excitation-contraction coupling but influenced cellular automaticity upon prolonged electrical stimulation. Conclusion Plasma derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Chronic co-incubation with Canakinumab had no beneficial effect on cellular Ca2+ signaling during excitation-contraction coupling. Funding Acknowledgement Type of funding sources: None.

THE IMPACT OF QUERCETIN ON THE FUNCTIONAL STATE OF CARDIOVASCULAR SYSTEM AND HEMOSTASE IN RATS WITH TYPE 2 DIABETES MELLITUS

Introduction. Type 2 diabetes mellitus (T2DM) increases the risk for atherosclerotic cardiovascular disease and other cardiovascular complications such as cardiac arrhythmias, heart failure, and thrombotic events. Quercetin (Q) possesses a wide range of multiple activities: anti-diabetic, anti-proliferative, anti-atherosclerotic, antioxidant, anti-inflammatory, anti-thrombotic, anti-apoptotic effects and is regarded as a candidate for the role of cardiovascular complications protecting agent.&#x0D; The aim of this study was to assess the effects of Q on the functional state of cardiovascular system and haemostasis in diabetic rats.&#x0D; Materials and Methods. T2DM was induced in Wistar rats by a high-caloric diet during 14 weeks combined with intraperitoneal injections of 25 mg/kg streptozotocin twice per week. All diabetic animals were divided into three groups: treated with solvent and with Q (in dose 10 and 50 mg/kg/day per os) for 8 weeks after diabetes induction. Fibrinogen concentration and induced euglobulin fibrinolysis time were measured in plasma using reagent kits. Electrocardiograms were recorded in leads II.&#x0D; Results. It was established that Q in dose 50 mg/kg b.w. prevents in the formation of sinus tachycardia in experimental animals. In addition, Q in both doses inhibits the development of myocardial diastolic dysfunction, which was confirmed by prolongation of T-P interval and a decrease of duration of the T wave in comparison with diabetic rats. Q in both doses restorated the processes of coagulations and fibrinolysis, as indicated by a decrease of fibrinogen levels and the time of thrombolysis compared to diabetic rats.&#x0D; Conclusions. Q, independently of dose, inhibits the development of myocardial diastolic dysfunction and reduces prothrombotic potential in rats with type 2 diabetes, which may ameliorate diabetic cardiovascular risk. This data justify the perspective of Q for the prevention and management of cardiovascular complications in patients with type 2 diabetes.

Impacts administration of Rifampicin on sperm DNA integrity and Male Reproductive System parameters in rats

Objective: Evaluate the impacts of rifampicin on certain sperm function parameters and to determine whether rifampicin has an impact on chromatin quality or sperm DNA integrity. Materials and Methods: Forty two male adult rats were subjected to this study. The entire rats were subjected to random division into six groups; four rifampicin- treated groups and two control groups. Rifampicin- treated groups were treated with a dose of either (27mg/kg/day) or (54mg/kg/day) and for each treatment dose, the treatment persists for either 14 days or 28 days. Certain parameters of sperm function including sperm concentration and sperm motility were assessed. Furthermore, analysis of sperm DNA integrity and chromatin quality were also studied. Results: No significant changes related to sperm concentration were observed when rifampicin was given in different doses and different durations. A significant change in sperm motility were recorded only when rifampicin was given in high dose for 28 days and there was a significant reduction in sperm progressive and total motility. Rifampicin showed a significant increase in sperm DNA staining capability when the dose and duration was increased. Administration of rifampicin in high dosage for 28 days represented in larger adverse impact on structure of sperm chromatin. Conclusion: Rifampicin could negatively affect male fertility potential in rats mainly through affecting the quality of sperm chromatin structure.

Complementary Therapeutic Effect of Polyherbal Supplement (Gasca D™) on Newly Diagnosed Type 2 Diabetic Patients on Lifestyle Modification: A Randomised Cohort Clinical Trial

Our previous studies have shown that Gasca D™; a polyherbal formulation made from three well known antidiabetic plants in Nigeria, possess anti-hyperglycemic, body weight and blood lipid lowering potentials in rats. In view of this, the present study was therefore designed to evaluate the complementary therapeutic efficacy of Gasca D™ supplementation with lifestyle modification in a clinical setting. The randomized cohort trial was conducted in sixty (60) newly diagnosed type 2 diabetic patients on life style modification as first-line therapy who willingly volunteered to participate. The subjects that satisfy our inclusion criteria were randomly assigned into Gasca D™ (GG) and lifestyle (LG) groups. The GG group received 2000 mg Gasca D™ capsules daily over a twelve weeks period whereas the LG group received none. Biochemical estimates were conducted on subjects to evaluate the safety and efficacy of the polyherbal supplement at the end of the intervention period. Mean fasting blood sugar (FBS) showed a decrease of 23.4% (p &lt; 0.05) in the GG group contrary to a 9.6% mean FBS observed in the LG (p &lt; 0.05) group. Variation in glycosylated hemoglobin (HbA1c) was in line with that of FBS. Safety of Gasca D™ was demonstrated by a normal renal and liver function profile in both groups. Our finding suggests that, Gasca D™ can successfully be used as an effective and safe complementary nutraceutical for the control of hyperglycemia in type 2 diabetic patients on life style modification.

COVID19-associated cardiomyocyte dysfunction, arrhythmias and the effect of Canakinumab.

BackgroundCardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive.Aims and methodsWe investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1β antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy.ResultsIsolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca2+ transient amplitudes and altered baseline [Ca2+] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca2+ release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca2+ release or Ca2+ signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity.ConclusionSerum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca2+ signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca2+ imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.

Chronic, Multi-Site Recordings Supported by Two Low-Cost, Stationary Probe Designs Optimized to Capture Either Single Unit or Local Field Potential Activity in Behaving Rats.

Rodent models of cognitive behavior have greatly contributed to our understanding of human neuropsychiatric disorders. However, to elucidate the neurobiological underpinnings of such disorders or impairments, animal models are more useful when paired with methods for measuring brain function in awake, behaving animals. Standard tools used for systems-neuroscience level investigations are not optimized for large-scale and high-throughput behavioral battery testing due to various factors including cost, time, poor longevity, and selective targeting limited to measuring only a few brain regions at a time. Here we describe two different “user-friendly” methods for building extracellular electrophysiological probes that can be used to measure either single units or local field potentials in rats performing cognitive tasks. Both probe designs leverage several readily available, yet affordable, commercial products to facilitate ease of production and offer maximum flexibility in terms of brain-target locations that can be scalable (32–64 channels) based on experimental needs. Our approach allows neural activity to be recorded simultaneously with behavior and compared between micro (single unit) and more macro (local field potentials) levels of brain activity in order to gain a better understanding of how local brain regions and their connected networks support cognitive functions in rats. We believe our novel probe designs make collecting electrophysiology data easier and will begin to fill the gap in knowledge between basic and clinical research.

A novel bone-thinning technique for transcranial stimulation motor-evoked potentials in rats

Transcranial electrical stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans, and even in animal studies, tcMEPs are used to evaluate neurological dysfunction. However, there is a dearth of reports on extended tcMEP recordings in both animal models and humans. Therefore, this study examined a new technique for stably recording tcMEPs over several weeks in six healthy female Sprague–Dawley rats. We thinned the skull bone using the skull base and spinal surgery technique to reduce electrical resistance for electrical stimulation. tcMEPs were recorded on days 1, 7, 14, 21, and 28 after surgery. The onset latency and amplitude of tcMEPs from the hindlimbs were recorded and evaluated, and histological analysis was performed. Stable amplitude and onset latency could be recorded over several weeks, and histological analysis indicated no complications attributable to the procedure. Thus, our novel technique allows for less invasive, safer, easier, and more stable extended tcMEP recordings than previously reported techniques. The presently reported technique may be applied to the study of various nerve injury models in rats: specifically, to evaluate the degree of nerve dysfunction and recovery in spinal cord injury, cerebral infarction, and brain contusion models.

Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin.

Pharmacologically active macromolecules, such as peptides, are still a major challenge in terms of designing a delivery system for their transport across absorption barriers and at the same time provide sufficiently high long-term stability. Spray freeze dried (SFD) lyospheres® are proposed here as an alternative for the preparation of fast dissolving porous particles for nasal administration of insulin. Insulin solutions containing mannitol and polyvinylpyrrolidone complemented with permeation enhancing excipients (sodium taurocholate or cyclodextrins) were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were highly spherical and mean diameters ranged from 190 to 250 µm, depending on the excipient composition. Based on the low density, lyospheres resulted in a nasal deposition rates of 90% or higher. When tested in vivo for their glycemic potential in rats, an insulin-taurocholate combination revealed a nasal bioavailability of insulin of 7.0 ± 2.8%. A complementary study with fluorescently labeled-dextrans of various molecular weights confirmed these observations, leading to nasal absorption ranging from 0.7 ± 0.3% (70 kDa) to 10.0 ± 3.1% (4 kDa). The low density facilitated nasal administration in general, while the high porosity ensured immediate dissolution of the particles. Additionally, due to their stability, lyospheres provide an extremely promising platform for nasal peptide delivery.

Advanced Development of Carboxylic Acid Functionalized Multiwall Carbon Nanotubes as Safe Inhalation Drug Carrier

Background: Multiwall Carbon Nanotubes (MWCNTs) have innovative characteristic features strongly associated with nanotechnology and drug delivery applications. Objectives: The current work was performed with an objective to assess the inhalation toxicity of multi-walled carbon nanotubes. Methods: Functionalization of multi-walled carbon nanotubes was carried out by the initial basic treatment with hydrochloric acid and nearly assessed by Infrared (IR) spectroscopy, mass spectroscopy, and Transmission electron microscopy (TEM) in comparison with pure multi-walled carbon nanotubes. The acute inhalation toxicity of these functionalized and pure multi-walled carbon nanotubes was assessed in Wistar rats. The parameters: hematology, liver function test, kidney function test, and histopathology observed, evaluated and interpreted for the toxicity study. Results: The functionalized multi-walled carbon nanotubes and pure multi-walled carbon nanotubes were nearly assessed by IR spectroscopy, mass spectroscopy, and TEM. The assessments affirmed and anticipated that the pure multi-walled carbon nanotube undergoes successful functionalization. Results obtained showed a remarkable difference in the ranges of hemoglobin and platelet. The acute inhalation toxicity study did not show any toxicity of functionalized multi-walled carbon nanotubes when compared to pure multi-walled carbon nanotubes. The results of acute inhalation toxicity studies did not show any significant changes also not demonstrated hazard potential in rats following acute exposures to the functionalized multi-walled carbon nanotubes and there is no significant toxicity. Because of basic treatment during functionalization all impurity gets removed. During functionalization addition of oxygen containing group and removal of carbon dioxide group occurs. Conclusion: Functionalized multi-walled carbon nanotubes can prove to be a novel, safe, and non-toxic carrier for the delivery of drugs by inhalation route.

Concordant neurophysiological signatures of cognitive control in humans and rats.

Progress towards understanding neural mechanisms in humans relevant to psychiatric conditions has been hindered by a lack of translationally-relevant cognitive tasks for laboratory animals. Accordingly, there is a critical need to develop parallel neurophysiological assessments of domains of cognition, such as cognitive control, in humans and laboratory animals. To address this, we developed a touchscreen-based cognitive (Eriksen Flanker) task in rats and used its key characteristics to construct a novel human version, with similar testing parameters and endpoints across species. We obtained continuous electroencephalogram (EEG) recordings, including local field potentials in rats, and compared electrophysiological signatures locked to stimulus onset and responses across species. We also assessed whether behavioral or physiological task effects were modulated by modafinil, which enhances aspects of cognitive function in humans. In both species, the task elicited expected flanker interference effects (reduced accuracy) during high-conflict trials. Across homologous neuroanatomical loci, stimulus-locked increases in theta power during high-conflict trials as well as error-related negative potentials were observed. These endpoints were not affected by modafinil in either species. Despite some species-specific patterns, our findings demonstrate the feasibility of a rat Flanker task as well as cross-species behavioral and neurophysiological similarities, which may enable novel insights into the neural correlates of healthy and aberrant behavior and provide mechanistic insights relevant to treatment.

Vertical-junction photodiodes for smaller pixels in retinal prostheses

Objective. To restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 μm pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled by (a) increasing the diode responsivity using vertical p–n junctions and (b) directing the electric field in tissue vertically. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field. Approach. Arrays of silicon photodiodes of 55, 40, 30, and 20 μm in width, with vertical p–n junctions, were fabricated. The electric field in the retina was directed vertically using a common return electrode at the edge of the device. Optical and electronic performance of the diodes was characterized in-vitro, and retinal stimulation threshold measured by recording the visually evoked potentials in rats with retinal degeneration. Main results. The photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A W−1, with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057 mW mm−2 with 10 ms pulses, independent of pixel size. Significance. Photodiodes with vertical p–n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 μm. Vertically oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of scaling down the photovoltaic pixels for subretinal stimulation.

Sufficient sampling for kriging prediction of cortical potential in rat, monkey, and human µECoG

Objective. Large channel count surface-based electrophysiology arrays (e.g. µECoG) are high-throughput neural interfaces with good chronic stability. Electrode spacing remains ad hoc due to redundancy and nonstationarity of field dynamics. Here, we establish a criterion for electrode spacing based on the expected accuracy of predicting unsampled field potential from sampled sites. Approach. We applied spatial covariance modeling and field prediction techniques based on geospatial kriging to quantify sufficient sampling for thousands of 500 ms µECoG snapshots in human, monkey, and rat. We calculated a probably approximately correct (PAC) spacing based on kriging that would be required to predict µECoG fields at 10% error for most cases (95% of observations). Main results. Kriging theory accurately explained the competing effects of electrode density and noise on predicting field potential. Across five frequency bands from 4–7 to 75–300 Hz, PAC spacing was sub-millimeter for auditory cortex in anesthetized and awake rats, and posterior superior temporal gyrus in anesthetized human. At 75–300 Hz, sub-millimeter PAC spacing was required in all species and cortical areas. Significance. PAC spacing accounted for the effect of signal-to-noise on prediction quality and was sensitive to the full distribution of non-stationary covariance states. Our results show that µECoG arrays should sample at sub-millimeter resolution for applications in diverse cortical areas and for noise resilience.