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该疾病 不仅给患者造成身体上的危害，还严重影响患者生活质量。 Epilepsy is a common disease of the nervous system. This disease not only causes physical harm to patients, but also seriously affects the quality of life of patients. 相关问题 ，例如癫痫的发作机制是怎样的？ So the problems related to the treatment and control of epilepsy, such as what is the mechanism of epilepsy? What nucleolus and channel proteins are involved in seizures? Are certain drugs effective in preventing or reducing the number of seizures? And so on are a series of important topics in medical research.
使用实验动物 造 癫痫模型 和方法： At present we know the following models and methods of epilepsy using experimental animals :
急性简单部分性癫痫模型 Acute simple partial epilepsy model
The salient feature of this model is the acute and convulsive discharge caused by cortical damage. The modeling method is to give a surface alarming agent to the cerebral cortex of rats or mice: for example, penicillin, bicuculline, azadirachtin and the like. However, after a long period of practice, the model is gradually not reused by scientific researchers because of its short pathogenic time and its long relationship with human epilepsy.
慢性简单部分性癫痫模型 2. Chronic simple partial epilepsy model
4% 的氢氧化铝， 1 到 2 周后可产生自发的反复性惊厥，可维持数年，该模型的发作症状，发作间 / 发作后皮层脑电波形和脑部病理改变、抗痫药物效果都类似与人类简单部分性癫痫，如果是想进行脑损伤病理，癫痫产生、过程、发病机制机理研究的研究人员，可以推荐使用该模型进行实验。 The modeling method is to implant bivalent metal ions (aluminum hydroxide, cobalt, zinc, tungsten, etc.) in the cerebral cortex of a cat or monkey, for example, inject 4% aluminum hydroxide in an appropriate part of the cerebral cortex , 1 to After 2 weeks, spontaneous recurrent seizures can be produced, which can be maintained for several years. The model's seizure symptoms, intercortical / post-seizure cortical EEG waveforms and brain pathological changes, and the effects of antiepileptic drugs are similar to those of human simple partial epilepsy Researchers who want to study the pathology of brain injury, epilepsy, processes, and pathogenesis can recommend this model for experiments.
复杂部分性癫痫模型： 3. Complex partial epilepsy model:
A. LTP ）、学习记忆等问题的最优模型。 Ignition model: Ignition model is currently recognized as the optimal model for studying brain cell excitability, plasticity and long-term enhancement ( LTP ), learning and memory. That is, in a certain brain region of the animal (such as the hippocampus, entorhinal cortex, piriform cortex, neocerebral cortex, basal nodules, mostly amygdala), repeated stimulation of subconvulsant intensity (usually electrical stimulation) causes animal rigidity and The process of clonic seizures. The model can be maintained for a long time until the animal's life.
B. ：与点燃法相比，诱发癫痫持续状态模型的操作要简单得多。 Epilepsy status model : Compared with the ignition method, the operation of the seizure status model is much simpler. KA ）（ 皮内、腹膜、静脉内给与 8-12mg/ K g 的 K A ）或匹鲁卡品（ 约 1% ， 30 mg/ K g ） 。 The most typical method is to inject a larger dose of kainic acid ( KA ) to the animal as a whole ( intradermally, peritoneally, or intravenously to a K of 8-12 mg / K g ) or pilocarpine ( about 1% , 30 mg / K g ) . 癫痫模型 的特点为连续的，复发的癫痫发作表现。 The induced persistent state epilepsy model is characterized by continuous, recurrent seizures. 持续状态发作过后延迟出现的自发性癫痫发作 是科研人员研究的兴趣所在 ，其大脑海马区形态学的损伤改变非常接近于人类颞叶癫痫的病理改变，但这一模型 也有它的 缺点， 比如 持续状态不易掌控，有时会造成动物死亡，同时对动物神经系统损害会很明显 等等 。 The delayed spontaneous seizures after the onset of persistent state are of interest to researchers. The morphological damage of the hippocampus in the brain is very close to the pathological changes of human temporal lobe epilepsy, but this model also has its shortcomings, such as The persistent state is not easy to control, sometimes it will cause animal death, and the damage to the animal's nervous system will be obvious . But so far, there is still a more applied modeling method.
全身强直 - 阵挛性惊厥模型： 4. Systemic tonic - clonic seizure model:
It is mainly divided into hereditary systemic convulsion model, maximum electrical shock model and chemical drug alarm model. The most commonly used model is the hereditary systemic seizure model. 、 Totterer(tg/tg) 小鼠和 GEPR 、 P77PMC 大鼠都是常用的模型动物。 DBA / 2J , Totterer (tg / tg) mice and GEPR , P77PMC rats are commonly used model animals.
我们现在已经使用某一 种 造模方法对大小鼠进行 了正确的 操作， 剩下的工作就看动物们的反应了，我们还要挑选已经成功造模的动物去进行后续的实验。 If we have used a certain modeling method to perform the correct operation on rats and mice , the rest of the work depends on the reactions of the animals. We must also select animals that have been successfully modeled for subsequent experiments. 年， Racine 将大鼠出现癫痫行为的严重程度分为 0 ～ V 级。 In 1978 , Racine classified the severity of epileptic behavior in rats as 0 to V. 级 , 咀嚼运动，即面部肌肉抽搐，包括眨眼、动须、节律性咀嚼等； II 级， I 级加点头运动， 即颈部肌肉抽搐； III 级， II 级加一侧前肢阵挛； IV 级， III 级加后肢站立并双侧前肢阵挛； V 级，双侧前肢阵挛加重，失去平衡跌倒。 Level I , chewing exercise, that is, facial muscle twitching, including blinking, whiskers, rhythmic chewing, etc .; Level II, level I plus nod movement, that is, neck muscle twitching; Level III, level II plus one forelimb clonic; IV Grade III, with hindlimbs standing and bilateral forelimb clonics; Grade V , bilateral forelimb clonics aggravating, losing balance and falling. This classification later became a standard for observing the seizure behavior of epilepsy models and judging whether the models were successful. Now this standard has been widely adopted by scholars from various countries.
KA 建立癫痫持续状态模型 后 ，将动物癫痫行为的严重程度按 Racine 描述 (0-V 级 ) ，一般的实验人员规定当动物符合 Racine III 级发作症状，维持 1h 以上，且在解除痫性发作后状态良好的动物则被称为造模成功的癫痫动物 (kindled animal) 。 Suppose we use KA to establish a model of epilepsy status , and describe the severity of epilepsy in animals according to Racine ( grade 0-V ) . The general experimenter stipulates that when the animal meets the symptoms of Racine class III seizures, it is maintained for more than 1 hour , and the epilepsy is removed Animals that are in good condition after a sexual attack are called kindled animals that have been successfully modeled .
大多数情况下 后续的实验内容可能包含动物的皮层脑电、核团脑电记录与分析以及病理切片，蛋白表达分析。 The model was successfully established. In most cases, the subsequent experimental content may include cortical EEG, nuclear EEG recording and analysis of animals, pathological sections, and protein expression analysis.
征 ： 动物的 脑电类似于人类脑电，人正常 脑电波形分为 δ 波： 0.5-4Hz; θ 波： 5-7Hz ； α 波： 8-13Hz ； β 波：13-30 H z；波形整齐、对称、同步，部分波形图如下 Let's talk about the basic characteristics of EEG in epilepsy animals : Animal EEG is similar to human EEG, and human normal EEG waveforms are divided into δ waves: 0.5-4Hz; θ waves: 5-7Hz ; α waves : 8-13Hz ; β wave: 13-30 H z; the waveform is neat, symmetrical, and synchronized, part of the waveform is shown below
- 慢波、多棘 - 慢波、尖 - 慢波等等。 The epilepsy-like discharge of epilepsy usually has abnormal waveforms, such as the typical spike wave, spike wave, spine - slow wave, multi-spike - slow wave, spike - slow wave, and so on.
1 为发作间期； 2 为强直期； 3 为阵挛期， 4 为发作后期 And the seizure process is different, the EEG waveforms can also be clearly distinguished. The EEG results in the middle of the figure below show a typical seizure pattern, 1 is the inter-seizure period; 2 is the tonic phase; 3 is the clonic phase , 4 is late onset
With clear EEG waveforms, it is convenient for us to identify seizures and compare drug efficacy.
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