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In epilepsy, a sudden burst of electrical activity in the brain leads to neurological and cardiorespiratory abnormalities. These abnormalities include seizures - abnormal electrical signals in the brain, arrhythmia - an irregular heartbeat, and apnea - transient breathing cessation, which can be evaluated by a multisystem monitoring method.
To perform multisystem monitoring in an animal model, begin with a restrained rabbit with pre-implanted electroencephalogram, or EEG, and electrocardiogram, or ECG, electrodes. The EEG and ECG electrodes help monitor real-time brain activity and heart rhythms, respectively. Next, attach an oximeter over the rabbit's right ear and a capnograph over the rabbit's nose and mouth to record respiratory parameters.
Shave the posterior surface of the rabbit's left ear to visualize the marginal ear vein. Wipe the ear with an antiseptic to sterilize the surface and dilate the vein. Then, insert a cannula into the ear vein and secure it. Connect the cannula to a perfusion system containing a seizure-inducing reagent. Now, inject the desired concentration of the reagent into the rabbit's vein and allow it to spread further into the brain.
Seizure-inducing molecules bind to the antagonist-modulatory site of gamma-aminobutyric acid, or GABA receptors, causing the prolonged depolarization of neurons. Thereafter, periodically increase the dose and carefully monitor the parameters to achieve visual evidence of epileptic abnormalities.
Before recording the EEG-ECG response to intravenous medication administration, shave the posterior surface of the rabbit's ear and use 70% ethanol to disinfect the site and to dilate the marginal ear vein. Carefully cannulate the marginal ear vein with a 25-gauge angiocatheter and place an injection plug at the end of the catheter. Tape a splint created from three rolled pieces of gauze to the ear to secure the catheter in place, and to hold the ear upright. Inject 1 milliliter of 10 USP units per mL of heparinized saline to keep the catheter patent.
When baseline recording has finished, inject saline supplemented with 1 to 10 mg/kg of the drug of interest into the catheter once every 10 minutes. After each dose, carefully monitor the video-EEG-ECG-capnography-oximetry for any neuro-cardiac, electrical, and respiratory abnormalities, or visual evidence of epileptiform activity. Note these changes in real-time as well as during post-analysis.
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