Orientation pinwheels in primary visual cortex of a highly visual marsupial.

Primary visual cortices in many mammalian species exhibit modular and periodic orientation preference maps arranged in pinwheel-like layouts. The role of inherited traits as opposed to environmental influences in determining this organization remains unclear. Here, we characterize the cortical organization of an Australian marsupial, revealing pinwheel organization resembling that of eutherian carnivores and primates but distinctly different from the simpler salt-and-pepper arrangement of eutherian rodents and rabbits. The divergence of marsupials from eutherians 160 million years ago and the later emergence of rodents and rabbits suggest that the salt-and-pepper structure is not the primitive ancestral form. Rather, the genetic code that enables complex pinwheel formation is likely widespread, perhaps extending back to the common therian ancestors of modern mammals.

Randomised clinical trial comparing the perioperative analgesic efficacy of oral tramadol and intramuscular tramadol in cats.

OBJECTIVES: The aim of this study was to evaluate the analgesic efficacy of oral tramadol in cats undergoing ovariohysterectomy. METHODS: Twenty-four female domestic cats, American Society of Anesthesiologists class I, aged 4-24 months, were included in this positive controlled, randomised, blinded clinical trial. Cats admitted for ovariohysterectomy were allocated to group oral tramadol (GOT, n = 12) or group intramuscular tramadol (GIMT, n = 12). In GOT, tramadol (6 mg/kg) was given orally 60 mins, and saline was given intramuscularly 30 mins, before induction of anaesthesia. In GIMT, granulated sugar in capsules was given orally 60 mins and tramadol (4 mg/kg) intramuscularly 30 mins before induction of anaesthesia. In both groups, dexmedetomidine (0.007 mg/kg) was given intramuscularly 30 mins before induction of anaesthesia with intravenous propofol. Anaesthesia was maintained with isoflurane in oxygen, and atipamezole (0.037 mg/kg) was given intramuscularly 10 mins after extubation. The UNESP-Botucatu multidimensional composite scale was used to conduct pain assessments before premedication and at 20, 60, 120, 240 and 360 mins post-extubation or until rescue analgesia was given. To compare groups, the 60 min postoperative pain scores and the highest postoperative pain scores were analysed via a two-tailed Mann-Whitney test, and the incidences of rescue analgesia were analysed via a Fisher's exact test; P <0.05. RESULTS: There was no significant difference between groups for the 60 min (P = 0.68) pain scores. The highest postoperative pain score was higher for GIMT compared with GOT (P = 0.04). Only two cats required rescue analgesia, both from GIMT. The incidence of rescue analgesia was not significantly different between groups (P = 0.46). CONCLUSIONS AND RELEVANCE: In the present study, preoperative administration of oral tramadol at 6 mg/kg to cats provided adequate analgesia for 6 h following ovariohysterectomy surgery.

Intravenous Acetaminophen Does Not Provide Adequate Postoperative Analgesia in Dogs Following Ovariohysterectomy.

(1) Objective: To investigate the analgesic effects of intravenous acetaminophen after intravenous administration in dogs presenting for ovariohysterectomy. (2) Methods: 14 ASA I client-owned female entire dogs. In this randomized, blinded, clinical study, dogs were given meperidine and acepromazine intramuscularly before induction of anesthesia with intravenous propofol. Anesthesia was maintained with isoflurane in oxygen. Intravenous acetaminophen 20 mg/kg or 0.9% NaCl was administered postoperatively. Pain assessments were conducted using the Glasgow Pain Scale short form before premedication and at 10, 20, 60, 120, and 180 min post-extubation or until rescue analgesia was given. The pain scores, times, and incidences of rescue analgesia between the groups was compared. Blood was collected before and 2, 5, 10, 20, 40, and 80 min after acetaminophen administration. Acetaminophen plasma concentration was quantified by liquid chromatography-mass spectrometry. The acetaminophen plasma concentration at the time of each pain score evaluation was subsequently calculated. (3) Results: There was no significant difference in pain scores at 10 min, highest pain scores, or time of rescue analgesia between groups. In each group, 3 dogs (43%) received rescue analgesia within 20 min. (4) Conclusions: Following ovariohysterectomy in dogs, there was no detectable analgesic effect of a 20 mg/kg dosage of intravenous acetaminophen administered at the end of surgery.

A simple method to provide positive end expiratory pressure to treat hypoxaemia in an anaesthetised Asian Elephant (Elephas maximus).

Hypoxaemia is a common complication in anaesthetised or immobilised elephants. It is presumably because of hypoventilation and ventilation-perfusion mismatch. To prevent hypoxaemia, orotracheal intubation and positive pressure ventilation are recommended. This case report describes a hypoxaemic period despite positive pressure ventilation in a 46-year-old female Asian elephant (Elephas maximus) anaesthetised with azaperone-etorphine, medetomidine and an etorphine constant rate infusion in lateral recumbency for a dental procedure. The hypoxaemia was corrected utilising positive end-expiratory pressure (PEEP) of 5 cm - 10 cm H2O, a technique that has not previously been reported in the management of anaesthetised elephants. PEEP decreases atelectasis, shunt fraction, and increases lung compliance. Positive end-expiratory pressure was achieved by partial occlusion of the tailpiece of a manually triggered demand valve ventilator during expiration. This is a simple effective method of generating PEEP and correcting hypoxaemia without the need for any additional specialised equipment. However, PEEP decreased arterial blood pressure and should be implemented with caution if arterial blood pressure is not monitored.

Slim electrodes for improved targeting in deep brain stimulation.

OBJECTIVE: The efficacy of deep brain stimulation can be limited by factors including poor selectivity of stimulation, targeting error, and complications related to implant reliability and stability. We aimed to improve surgical outcomes by evaluating electrode leads with smaller diameter electrode and microelectrodes incorporated which can be used for assisting targeting. APPROACH: Electrode arrays were constructed with two different diameters of 0.65 mm and the standard 1.3 mm. Micro-electrodes were incorporated into the slim electrode arrays for recording spiking neural activity. Arrays were bilaterally implanted into the medial geniculate body (MGB) in nine anaesthetised cats for 24-40 h using stereotactic techniques. Recordings of auditory evoked field potentials and multi-unit activity were obtained at 1 mm intervals along the electrode insertion track. Insertion trauma was evaluated histologically. MAIN RESULTS: Evoked auditory field potentials were recorded from ring and micro-electrodes in the vicinity of the medial geniculate body. Spiking activity was recorded from 81% of the microelectrodes approaching the MGB. Histological examination showed localized surgical trauma along the implant. The extent of haemorrhage surrounding the track was measured and found to be significantly reduced with the slim electrodes (541 ± 455 µm vs. 827 ± 647 µm; P < 0.001). Scoring of the trauma, focusing on tissue disruption, haemorrhage, oedema of glial parenchyma and pyknosis, revealed a significantly lower trauma score for the slim electrodes (P < 0.0001). SIGNIFICANCE: The slim electrodes reduced the extent of acute trauma, while still providing adequate electrode impedance for both stimulating and recording, and providing the option to target stimulate smaller volumes of tissue. The incorporation of microelectrodes into the electrode array may allow for a simplified, single-step surgical approach where confirmatory micro-targeting is done with the same lead used for permanent implantation.

Author Correction: Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Two-point ultrasound-guided transversus abdominis plane injection in canine cadavers - a pilot study.

OBJECTIVE: This study evaluated the spread of a two-point transversus abdominis plane (TAP) injection in canine cadavers. Compared with previous techniques, the two-point TAP injection was developed to increase the consistency of local anaesthetic spread to the nerve segments T11, T12, L1, L2 and L3. STUDY DESIGN: Prospective experimental trial. ANIMALS: Five fresh canine cadavers. METHODS: Two-point TAP injections were performed under ultrasound guidance by a single trained individual in canine cadavers (15.7-43.0 kg). Each hemi-abdomen was infiltrated and evaluated independently for a total of 10 evaluations of the technique. The first injection was performed at the level of the costo-chondral junction of the thirteenth rib, and the second injection was performed cranial to the tuber coxae. Each injection comprised 0.3 mL kg-1 methylene blue solution (0.0015 mg mL-1). Ten minutes after the injections, abdominal wall dissection was performed, and any nerves stained for a minimum of 10 mm along their long axis were identified and recorded. RESULTS: During all injections, separation of the internal oblique and transversus abdominis muscles was observed on ultrasound. On dissection, branches of T12, T13, L1, L2 and L3 were adequately stained in 30%, 100%, 100%, 90% and 90% of injections, respectively. No staining of branches of T11 occurred in any of the cadavers. In one hemi-abdomen, branches of L1 and L3, but not L2, were stained. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that the two-point TAP injection delivers consistent dye dispersion to adequately stain branches of T13, L1, L2 and L3, with no coverage of T11 and poor coverage of T12, in fresh canine cadavers. An in vivo study using local anaesthetic should be performed to evaluate the analgesic efficacy of this technique in mid to caudal abdominal surgeries.

Content validation of a Critical Appraisal Tool for Reviewing Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain.

INTRODUCTION: This article reports the content validation of a Critical Appraisal Tool designed to Review the quality of Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain and provide guidance as to the strengths and weakness of findings. The CATRAS quality items encompass 3 domains: level of evidence, methodological soundness, and grading of the pain assessment tool. OBJECTIVES: To validate a critical appraisal tool for reviewing analgesia studies involving subjects incapable of self-reporting pain. METHODS: Content validation was achieved using Delphi methodology through panel consensus. A panel of 6 experts reviewed the CATRAS in 3 rounds and quantitatively rated the relevance of the instrument and each of its quality items to their respective domains. RESULTS: Content validation was achieved for each item of the CATRAS and the tool as a whole. Item-level content validity index and kappa coefficient were at least greater than 0.83 and 0.81, respectively, for all items except for one item in domain 2 that was later removed. Scale-level content validity index was 97% (excellent content validity). CONCLUSIONS: This 67-item critical appraisal tool may enable critical and quantitative assessment of the quality of individual analgesia trials involving subjects incapable of self-reporting pain for use in systematic reviews and meta-analysis studies.

Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable.

Recent work has demonstrated the feasibility of minimally-invasive implantation of electrodes into a cortical blood vessel. However, the effect of the dura and blood vessel on recording signal quality is not understood and may be a critical factor impacting implementation of a closed-loop endovascular neuromodulation system. The present work compares the performance and recording signal quality of a minimally-invasive endovascular neural interface with conventional subdural and epidural interfaces. We compared bandwidth, signal-to-noise ratio, and spatial resolution of recorded cortical signals using subdural, epidural and endovascular arrays four weeks after implantation in sheep. We show that the quality of the signals (bandwidth and signal-to-noise ratio) of the endovascular neural interface is not significantly different from conventional neural sensors. However, the spatial resolution depends on the array location and the frequency of recording. We also show that there is a direct correlation between the signal-noise-ratio and classification accuracy, and that decoding accuracy is comparable between electrode arrays. These results support the consideration for use of an endovascular neural interface in a clinical trial of a novel closed-loop neuromodulation technology.

In situ handheld three-dimensional bioprinting for cartilage regeneration.

Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three-dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue-engineering techniques at the time and location of need. We have created a hand-held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single-session surgery. This pilot study assessed the ability of the biopen to repair a full-thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical-sized full-thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand-held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra- or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.

The ovine motor cortex: A review of functional mapping and cytoarchitecture.

In recent years, sheep (Ovis aries) have emerged as a useful animal model for neurological research due to their relatively large brain and blood vessel size, their cortical architecture, and their docile temperament. However, the functional anatomy of sheep brain is not as well studied as that of non-human primates, rodents, and felines. For example, while the location of the sheep motor cortex has been known for many years, there have been few studies of the somatotopy of the motor cortex and there were a range of discrepancies across them. The motivation for this review is to provide a definitive resource for studies of the sheep motor cortex. This work critically reviews the literature examining the organization of the motor cortex in sheep, utilizing studies that have applied direct electrical stimulation and histological methods A clearer understanding of the sheep brain will facilitate and progress the use of this species as a scientific animal model for neurological research.

Influence of two administration rates of propofol at induction of anaesthesia on its relative potency in cats: a pilot study.

Objectives This was a randomised, blinded trial to investigate the influence of administration rate on the dose of propofol required for the orotracheal intubation of cats. Methods Twenty-four female domestic cats undergoing ovariohysterectomy were premedicated with oral tramadol (6 mg/kg) or intramuscular tramadol (4 mg/kg), and intramuscular dexmedetomidine (0.007 mg/kg). Oral or intramuscular (IM) tramadol was administered 60 or 30 mins prior to induction of anaesthesia, respectively. Dexmedetomidine was administered 30 mins prior to anaesthetic induction. Sedation scores were established prior to anaesthesia induction with propofol intravenously at 4 mg/kg/min (fast) or 1 mg/kg/min (slow) to effect until orotracheal intubation was achieved without coughing. If coughing occurred, the intubation process was paused for 15 s. Four groups were determined: IM tramadol/propofol fast (GIMF, n = 6); IM tramadol/propofol slow (GIMS, n = 6); oral tramadol/propofol fast (GOF, n = 6); oral tramadol/propofol slow (GOS, n = 6). The Shapiro-Wilk test was used to evaluate for normality of residuals. Sedation scores and propofol anaesthetic induction doses were compared between GIMF and GIMS groups, and between GOF and GOS groups using the Mann-Whitney test and the t-test, respectively ( P = 0.05). The presence of hypotension (mean arterial blood pressure <60 mmHg) or apnoea (no breathing for 30 s or more) within the first 15 mins postintubation was recorded. Results The median sedation scores for GIMF and GOF were not significantly different compared with those for GIMS ( P = 0.94) and GOS ( P = 0.70). However, the mean ± SD propofol anaesthetic induction doses were higher in GIMF (9.1 ± 1.8 mg/kg) and GOF (7.9 ± 1.7 mg/kg) than in GIMS (5.1 ± 1.5 mg/kg; P <0.01) and GOS (5.4 ± 0.3 mg/kg; P <0.01). No hypotension or apnoea were detected. Conclusions and relevance Using the slower anaesthetic induction rate resulted in an increase in propofol relative potency.

Influence of two administration rates of alfaxalone at induction on its relative potency in cats: a pilot study.

Objectives The aim of the study was to evaluate, in a controlled, randomised, masked clinical trial, the influence of administration rate of alfaxalone at induction on its relative potency in cats and to report the incidence of cardiorespiratory adverse effects. Methods Twelve healthy female domestic cats admitted for ovariohysterectomy were premedicated with buprenorphine 20 µg/kg intramuscularly and alfaxalone 3.0 mg/kg subcutaneously. Sedation scores were established (using a published scale ranging from 1 [no sedation] to 5 [profound sedation]) prior to anaesthesia induction with alfaxalone intravenously at 2 mg/kg/min (group A2; n = 6) or 0.5 mg/kg/min (group A0.5; n = 6) to effect until orotracheal intubation was achieved. Sedation scores and alfaxalone induction doses were compared between the groups, using a Mann-Whitney exact test. Results are reported as median and range. Presence of apnoea (no breathing for more than 30 s) or hypotension (mean arterial blood pressure <60 mmHg) within 5 mins postintubation was also reported. Results Although sedation scores (1.5 [range 1.0-3.0] and 2.5 [range 1.0-3.0] for A2 and A0.5, respectively) were not significantly different ( P = 0.32), cats in group A2 required significantly more alfaxalone (4.3 mg/kg [range 3.4-7.0 mg/kg]) than group A0.5 (2.1 mg/kg [range 1.5-2.5 mg/kg]) ( P = 0.002). Two cats in each group presented postinduction apnoea, and two cats in group A2 and three cats in group A0.5 presented postinduction hypotension. Conclusions and relevance The use of a slower induction infusion rate resulted in an increase in the alfaxalone relative potency without obvious cardiorespiratory benefit.

Evaluation of the Biocompatibility of Polypyrrole Implanted Subdurally in GAERS.

This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side. After a period of seven weeks, rats are euthanized and parallel series of coronal sections are cut throughout the implant site. Four series of 15 sections are histological (hematoxylin and eosin) and immunohistochemically (neuron-specific nuclear protein, glial fibrillary acidic protein, and anti-CD68 antibody) stained and evaluated by three investigators. The results show that implanted PPy mats do not induce obvious inflammation, trauma, gliosis, and neuronal toxicity. Therefore the authors conclude the PPy used offer good histocompatibility with central nervous system cells and that PPy sheets can be used as intracranial, AED delivery implant.

Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin.

The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures.

Evaluation of the influence of atipamezole on the postoperative analgesic effect of buprenorphine in cats undergoing a surgical ovariohysterectomy.

OBJECTIVE: To evaluate the influence of atipamezole on postoperative pain scores in cats. STUDY DESIGN: Controlled, randomized, masked clinical trial. ANIMALS: Twelve healthy female domestic cats. METHODS: Cats admitted for ovariohysterectomy (OVH) surgery were randomly allocated to group atipamezole (n = 6) or group saline (n = 6) and were premedicated with buprenorphine 20 µg kg(-1) intramuscularly (IM) and alfaxalone 3.0 mg kg(-1) subcutaneously (SC). Anaesthesia was induced with alfaxalone intravenously (IV) to effect and maintained with isoflurane in oxygen. Ten minutes after extubation, cats from group atipamezole received IM atipamezole (0.0375 mg kg(-1) ) whereas group saline received an equivalent volume [0.0075 mL kg(-1) (0.003 mL kg(-1) IM)] of 0.9% saline. A validated multidimensional composite scale was used to assess pain prior to premedication and postoperatively (20 minutes after extubation). If postoperative pain scores dictated, rescue analgesia consisting of buprenorphine and meloxicam were administered. Pain score comparisons were made between the two groups using a Mann-Whitney exact test. Results are reported as the median and range. RESULTS: Preoperatively, all cats scored 0. At the postoperative pain evaluation, the pain scores from group atipamezole [16 (range, 12-20)] were not significantly different from group saline [18 (range, 15-23)] (p = 0.28). All cats required rescue analgesia post-operatively. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole (0.0375 mg kg(-1) IM) administration did not significantly affect the postoperative pain scores in cats after OVH. Preoperative administration of buprenorphine (20 µg kg(-1) IM) did not provide adequate postoperative analgesia for feline OVH.

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity.

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging.

Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions.

Injectable phenytoin loaded polymeric microspheres for the control of temporal lobe epilepsy in rats.

PURPOSE: Epilepsy is a prevalent neurological disorder with a high frequency of drug resistance. While significant advancements have been made in drug delivery systems to overcome anti-epileptic drug resistance, efficacies of materials in biological systems have been poorly studied. The purpose of the study was to evaluate the anti-epileptic effects of injectable poly(epsilon-caprolactone) (PCL) microspheres for controlled release of an anticonvulsant, phenytoin (PHT), in an animal model of epilepsy. METHODS: PHT-PCL and Blank-PCL microspheres formulated using an oil-in-water (O/W) emulsion solvent evaporation method were evaluated for particle size, encapsulation efficiency, surface morphology and in-vitro drug release profile. Microspheres with the most suitable morphology and release characteristics weresubsequently injected into the hippocampus of a rat tetanus toxin model of temporal lobe epilepsy. Electrocorticography (ECoG)from the cerebral cortex were recorded for all animals. The number of seizure events, severity of seizures, and seizure duration were then compared between the two treatment groups. RESULTS: We have shown that small injections of drug-loaded microspheres are biologically tolerated and released PHT can control seizures for the expected period of time that is in accord with in-vitro release data. CONCLUSION: The study demonstrated the feasibility of polymer-based delivery systems incontrolling focal seizures.

Evaluation of an automated spike-and-wave complex detection algorithm in the EEG from a rat model of absence epilepsy.

The aim of this prospective blinded study was to evaluate an automated algorithm for spike-and-wave discharge (SWD) detection applied to EEGs from genetic absence epilepsy rats from Strasbourg (GAERS). Five GAERS underwent four sessions of 20-min EEG recording. Each EEG was manually analyzed for SWDs longer than one second by two investigators and automatically using an algorithm developed in MATLAB®. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the manual (reference) versus the automatic (test) methods. The results showed that the algorithm had specificity, sensitivity, PPV and NPV >94%, comparable to published methods that are based on analyzing EEG changes in the frequency domain. This provides a good alternative as a method designed to mimic human manual marking in the time domain.