动物模型,急性癫痫 z-bo 2020-08-03 775

　　[Overview] Acute epilepsy models are usually acute epileptic seizure models that can induce epilepsy with one treatment, including maximum electric shock (MES) epilepsy models and pentylenetetrazol (PTZ) epilepsy models.

　　(1) The largest electric shock epilepsy model

　　[Modeling mechanism] Place electrodes on the animal’s ears or eyes, and apply a strong current to the electrodes to stimulate the brain in a short time, and apply tension to the animals’ hind limbs. Cause convulsions.

　　[Modeling method] Perform pharmacological and physiological experiments with an electric shock meter or a multi-function instrument, introduce the wire into the alternating current, connect the output wire to the alligator clip, wet it with saline, and then clip it in the rat ear or in small increments The clamped disc-shaped concave corneal electrode is in contact with the double cornea (the cornea is anesthetized with tetracaine), and then energized. This may cause typical tonic attacks of forelimb flexion and hindlimb extension in mice or rats. The electrical stimulation parameters are usually: 50mA for mice, 150mA for rats, 60Hz, 80-120V (180V for rats), and the stimulation time is 0.2-0.3 seconds. The seizure process can be divided into incubation period, tonic, clonic and post-convulsive suppression. Observation index: The observation index is whether the hind limbs of the animal are stiff. If a certain drug can prevent its development, it indicates that the drug has an anti-MES effect.

　　[Model Features] MES model is one of the most commonly used and studied models. It is usually used to simulate human tonic-clonic seizures and drug screening tonic-clonic seizures. The classic anti-epileptic drug phenytoin sodium was discovered through the MES model. [Model evaluation and application] The method of establishing MES epilepsy model is simple, and the screening efficiency of antiepileptic drugs is high. The acute epilepsy model also has its disadvantages. The MES model has a great influence on drugs that act on ion channels, and may ignore other antiepileptic drugs (aminocaproic acid, tegabine, etc.). The MES epilepsy model screens drugs that are not suitable for anticonvulsant seizures. For example, in the MES model, the N-methyl-D-aspartate (NMDA) receptor antagonist is effective, but in the kindling model and clinical trials, the antagonist has no obvious anti-epileptic effect. It should be emphasized that the acute epilepsy model cannot imitate the entire process of human epilepsy development, nor can it imitate the pathophysiological process of refractory and drug-resistant epilepsy. (2) Pentylenetetrazol epilepsy model [modeling mechanism] PTZ is a tetrazole derivative that, when administered systemically, shows certain seizure effects in mice, rats, cats and primates. In mice, the intravenous dose of PTZ that causes clonic convulsions is 50 mg/kg, and the dose of tonic-clonic convulsions is 90 mg/kg. The subcutaneous dose that causes clonic convulsions is 85 mg/kg in mice and 70 mg/kg in rats. kg.

　　[Modeling method] PTZ mainly acts on the brainstem and forebrain to enhance the promotion of excitatory synapses and cause seizures. Methods: 18-25g mice, eat freely before the experiment, fasted during the experiment, and quickly injected 0.5% PTZ saline (38mg/kg) through the tail vein, which caused 97% of the mice to have seizures. .. Observation index: The stiffness of the hind limbs is an observation index that can prevent the efficacy of the drug. [Model Features] The PTZ model can simulate the extensive seizures of human myoclonic epilepsy, and the clinically used ethanesulfonimide was discovered from this model.

　　[Evaluation and Application of Model] PTZ epilepsy model is easy to prepare, and the screening efficiency of anti-epileptic compounds is high. In the past few decades, MES and PTZ models have been used as the gold standard for initial screening of epilepsy drugs. The PTZ model is a classic animal model of epilepsy for screening non-convulsive seizures. It also has its shortcomings: Lamotrigine has not been shown to have the effect of anti-convulsive seizures, but there are tegabine and aminocaproic acid. It seems obvious in the PTZ model that the effect of anticonvulsant epilepsy is clinically manifested as a deterioration of the non-convulsive epilepsy state.