Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Sheryl S. Smith in Neurosteroid Effects in the Central Nervous System, 2003
It was only within the last two decades that the reported rapid (seconds) onset of action of steroids was found to be mediated via an interaction with GABAA receptor complexes (GRCs). The initial in vitro evidence was provided by electrophysiological studies demonstrating enhancement of GABA-stimulated chloride conductance by the synthetic steroid anesthetic alfaxalone (3a-hydroxγ-5α-pregnane-11,20-dione) in rat brain.5 These findings soon were extended to both the 5α-and 5β-reduced, 3α-hydroxy metabolites of progesterone and deoxycorticosterone. Subsequent studies identified these neuroactive steroids as the most potent GABA–agonist steroid modulators at the GRC.
Induction of Anesthesia
Michele Barletta, Jane Quandt, Rachel Reed in Equine Anesthesia and Pain Management, 2023
Alfaxalone: This agent is an agonist at the GABA receptor, providing hypnosis and muscle relaxation similar to that of propofol. Similar to propofol, it can be used in combination with ketamine.Use of alfaxalone alone is quite costly, requires a large volume, and can cause myoclonus in the induction and recovery periods; therefore, it is not recommended.
Digital Subtracted Angiography of Small Animals
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
Small animal DSA imaging is performed under anesthesia, which is of utmost importance for optimal image acquisition. Compulsory fasting is not required prior to anesthesia, as rodents do not possess a vomiting reflex. Premedication (administration of drugs prior to anesthesia) with anticholinergic drugs can be used to maintain the heart rate and decrease gut motility, while tranquilizers can relieve anxiety, create calmness, and reduce the dose of the anesthetic required. Nonsteroidal anti-inflammatory drugs (e.g., carprofen) can be given to provide longer-term pain relief (up to 24 h), especially in cases of minor surgery (Tremoleda et al. 2012). Both injectable and inhaled anesthetics can be used in rodents. Inhalation anesthesia is considered the method of choice for imaging protocols in laboratory rodents. Highly volatile agents such as halothane and isoflurane can be administered to the animals using a carrier gas (usually oxygen) through a breathing circuit with an integrated vaporizer that permits the regulation of concentration and flow. The suggested flow rate for small animals is 0.5–1.5 L/min. Isoflurane is the preferred general anesthetic agent for cardiovascular studies, because it causes less cardiac function depression than injectable agents. Nonetheless, isoflurane demonstrates an inhibitory effect on peripheral resistance, and therefore decreases blood pressure (Kersten et al. 1996). Injectable agents include fentanyl/fluanisone- and ketamine-based combinations. Usually, the intraperitoneal infusion of xylazine hydrochloride (10 mg/kg body weight) and ketamine (100 mg/kg body weight) produces safe anesthesia with good analgesic and light sedative effect. Fentanyl/fluanisone in combination with benzodiazepine (midazolam or diazepam) is also licensed for surgical anaesthesia in rodents. The combination of ketamine with midazolam can also be used to provide 20–30 min of light anaesthesia in rodents. Supplemental doses of both the aforementioned anesthetic regimens or intermittent intravenous administration of low propofol doses are usually necessary to maintain a uniform level of anesthesia in cases of prolonged imaging. Other injectable agents that that can be used are alfaxalone and tribromoethanol. Optimal imaging requires not only selecting the appropriate anaesthetic regimen, but also using monitoring systems during image acquisition. Monitoring systems are especially important for longitudinal protocols of repeated anesthesia where the exposure of ionizing radiation and the repeated use of contrast agents and anesthetic drugs can have consequences on the animal’s physiology and its response to anesthesia. Pulse oximetry provides a simple method to measure oxygen saturation levels, and thus monitor anesthesia. Additionally, the investigator should maintain direct visual contact and access to the animal during imaging to assess basic parameters such as the depth and character of respiratory rate, heart rate, and body temperature. A thermoregulated surgical table is useful for maintaining steady body temperature.
Systemic and microvascular comparison of Lactated Ringer’s solution, VIR-HBOC, and alpha-alpha crosslinked haemoglobin-based oxygen carrier in a rat 10% topload model
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Bjorn K. Song, W. Richard Light, Kim D. Vandegriff, Joe Tucker, William H. Nugent
Animals were induced to anaesthesia with 1–5% isoflurane in air for initial pre-operative preparation and cannulations. Anaesthetic, alfaxalone acetate (Alfaxan, Schering-Plough Animal Health, Welwyn Garden City, UK), was infused continuously intravascularly at 0.1 mg/kg/min through a femoral vein cannula. Alfaxan is ideal for physiological studies focussed on cardiopulmonary and vascular function since it is minimally depressive per an appropriate anaesthetic depth—heel but not toe pinch response. The continuous rate of infusion allows for better control and consistency compared to bolus infusions. It has been used by our group in multiple topload and long term rat studies [19,20,24–27] and recently in an unpublished swine model of haemorrhagic shock. A femoral artery cannula, which was not used for infusion and kept patent with heparinized phosphate-buffered saline (20 IU heparin/mL), was connected to a pressure transducer for monitoring of systemic circulatory variables with a multichannel physiological monitoring system (BIOPAC MP-150, BIOPAC Systems, Goleta, CA). The jugular vein was cannulated for TL fluid infusions. A tracheal tube (PE-240) was inserted to maintain airway patency; animals continued to inspire room air and were not artificially ventilated. After experimentation, animals were euthanized with a dose of Euthasol (150 mg/kg, pentobarbital component, intravenously; Delmarva, Midlothian, Virginia).
Microvascular and systemic responses to novel PEGylated carboxyhaemoglobin-based oxygen carrier in a rat model of vaso-occlusive crisis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
William H. Nugent, Ronald Jubin, Peter J. Buontempo, Friedericke Kazo, Bjorn K. Song
Animals were inducted in anaesthesia with 1–5% isoflurane in medical air for initial pre-operative preparation and cannulations and were switched over to alfaxalone acetate (Alfaxan, Schering-Plough Animal Health, Welwyn Garden City, UK), which was continuously infused I.V. at 0.1 mg/kg/min through a femoral vein cannula for the duration of the experiment. A femoral artery cannula was connected to a pressure transducer to monitor systemic circulatory variables via a multichannel physiological monitoring system (BIOPAC MP-150, BIOPAC Systems, Goleta, CA). The carotid artery and jugular vein were cannulated for blood withdrawal and HbSS RBC infusions, respectively. A tracheal tube was inserted to maintain airway patency; however, animals were not artificially ventilated. After experimentation, animals were euthanized with a lethal dose of Euthasol (150 mg/kg, pentobarbital component, I.V.; Delmarva, Midlothian, Virginia).
Comparative effects of various absorbable threads in a rat model
Published in Journal of Cosmetic and Laser Therapy, 2019
Jung Jin Shin, Tae Jun Park, Bo Young Kim, Chang Min Kim, Dong Hye Suh, Sang Jun Lee, Hye-Rim Moon, Hwa Jung Ryu
Ten 8-week-old Sprague Dawley (SD) rats were purchased ((weight 200 g, Orient Bio Inc., Gyeonggi-do, South Korea). Thread insertion at the back of the rat was performed under general anesthesia with intramuscular injection of alfaxalone and xylazine (0.10 ml/kg). After shaving, the dorsal skin of each rat was divided into five different compartments and various threads were inserted into its respective position after making a small incision. Tissue samples including the thread and the surrounding tissues were harvested through punch biopsy for histological examination at 1, 2, and 12 weeks after the procedure. Tissue samples for hematoxylin and eosin (H&E) staining microscopy analysis were immediately fixed in 10% formalin. Samples for Col1A1, Col3A1, and TGF-b1 quantification were embedded in optimal cutting temperature embedding medium (Tissue-Tek OCT Compound Miles, Naperville, IL) and immediately frozen using liquid nitrogen and stored at −80°C.
Related Knowledge Centers
- Allosteric Modulator
- Anesthesia
- Gaba Receptor Agonist
- Gabaa Receptor
- Premedication
- Circulatory System
- Respiratory System
- Neurosteroid
- General Anaesthetic
- Injection