伽玛刀低剂量照射对致痫大鼠海马中谷氨酸、γ-氨基丁酸的影响
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摘要
癫痫是一组反复发作的以神经元异常放电所致的发作性脑功能障碍为特征的临床综合征,同时伴有脑血流、代谢及神经递质等一系列的生理、生化改变。它是神经科仅次于脑血管疾病的第二高发疾病,发病率为0.5%-1.0%,其中20%-25%的癫痫是药物难治性的,严重影响患者的生活质量。我国约有900万癫痫患者。癫痫患者及其家人在社会生活中承受着巨大的心理压力,给医疗、家庭及社会带来了沉重的负担。
癫痫的发病机制到目前为止仍然没有明确,但癫痫发作的两个重要特征是神经元兴奋性增高和高度同步化放电,这已得到多数学者的认同。谷氨酸(Glutamate, Glu)是脑内最主要的兴奋性氨基酸类递质。脑内超过50%的突触以Glu为递质。几乎所有的兴奋性神经元均是谷氨酸能神经元。Glu对于维持神经元的正常兴奋性有着至关重要的作用。然而过多的Glu聚集在细胞外则可能导致惊厥。γ-氨基丁酸(γ-amino butyric acid, GABA)是中枢神经系统最重要的抑制性神经递质,在阻断兴奋的扩散及传导过程中起决定性作用。GABA的合成减少,可使神经元的兴奋得不到正常控制,导致癫痫的发作。
目前癫痫发作的控制仍以长期服药为主,常用的一线抗癫痫药(AEDs)可以使70%-80%的癫痫发作得以控制,但长期用药也会给患者带来严重的不良反应,并且仍有20%-25%的癫痫是药物难治性的。随着医学影像技术和脑电生理技术的发展,对致痫灶定位已越来越准确,采用外科手术治疗难治性癫痫已成为癫痫治疗的一种重要手段。但手术的风险性是无法避免的,除了常规神经外科开颅手术的并发症如出血、感染、肢体运动功能障碍、颅神经功能障碍等,还可见精神情绪异常、语言功能障碍、智力和记忆力下降等,发生率为0.5%-20.0%。这就需要探索更安全、有效的治疗方法。
伽玛刀放射外科手术是一种微创、安全、定位准确的治疗手段,且具有可重复性的优点。可以在很小的容积内集中、精确的进行照射,对周边脑组织不造成损伤,对神经功能的影响轻微。伽玛刀放射外科治疗癫痫的安全性、有效性在动物实验和临床研究中早有报道。更重要的是,在伽玛刀治疗后,患者住院时间短,恢复快,费用低,不会影响其生活质量。近10年来,应用伽玛刀低剂量照射治疗癫痫的报告逐渐增多,多数学者认为10Gy的剂量小范围照射不产生脑坏死灶,可控制癫痫发作,安全、无并发症。为了进一步研究伽玛刀低剂量照射的抗癫痫作用及探讨其是否通过调节兴奋性神经递质和抑制性神经递质的平衡发挥抗癫痫作用,本实验采用氯化锂-匹罗卡品(Li-Pilo)癫痫大鼠模型进行研究伽玛刀低剂量照射对致痫大鼠海马中Glu、GABA的影响,从而在神经递质水平讨论伽玛刀的抗癫痫机制,为伽玛刀治疗癫痫提供理论依据。
将105只SPF级健康成年雄性Wistar大鼠随机分为两组即对照组(25只)、模型组(80只)。对照组采用腹腔注射生理盐水,模型组采用腹腔注射氯化锂溶液(127mg/kg)和匹罗卡品(30mg/kg)。将成功建立的50只癫痫大鼠模型再随机分为两组,即照射组(25只)、非照射组(25只)。对照组、照射组、非照射组各随机分为5个小组,即伽玛刀照射后1天组、1周组、2周组、4周组、8周组,每小组5只。
造模成功后,观察一段时间,大鼠模型出现反复的癫痫发作后,在麻醉状态下将照射组大鼠固定于大鼠专用的伽玛刀定位架上,进行脑冠状位磁共振成像连续扫描,确定照射靶区(左侧海马)三维坐标。然后实施伽玛刀照射,采用4 mm准直器,设一个靶点,周边剂量20 Gy,等剂量曲线80%,中心剂量25Gy。
在相应时间点(伽玛刀照射后1天、1周、2周、4周、8周),麻醉状态下开颅取海马组织,称重,制备匀浆液,先后加内标高丝氨酸、甲醇分别按10000 r/min,离心5min,取100μL上清液于液相色谱样品瓶中进行检测。
模型组大鼠：80只大鼠有55只大鼠造模时均出现Racine分级标准Ⅳ级以上的癫痫发作,1周后出现反复的癫痫发作,并逐渐达到Racine分级标准Ⅲ级以上,为了组间的均衡性,随机剔除5只,有50只纳入本研究对象。经过伽玛刀照射2周后,照射组大鼠癫痫发作程度逐渐减轻,降为Ⅱ-Ⅲ级；伽玛刀照射4周后,发作程度为Ⅰ-Ⅱ级；而非照射组大鼠癫痫发作程度始终在Ⅲ级以上。
伽玛刀照射后第2周,照射组和非照射组大鼠海马中Glu含量均高于对照组,照射组低于非照射组,差异具有统计学意义(P<0.05)；照射组和非照射组GABA含量均低于对照组,照射组高于非照射组,差异具有统计学意义(P<0.05)。
伽玛刀照射后第4、8周,照射组海马中Glu呈降低趋势、GABA呈上升趋势,与非照射组、对照组比较差异均有统计学意义(P<0.05)。
1、本研究通过实验性癫痫大鼠模型研究伽玛刀低剂量照射的抗癫痫效应,发现伽玛刀低剂量照射不仅可以减轻癫痫大鼠的发作程度,而且没有发生因为伽玛刀照射引起的严重并发症导致大鼠死亡,进一步说明了伽玛刀低剂量照射治疗癫痫的安全性、有效性。
2、非照射组大鼠海马中Glu含量逐渐增加,与对照组比较具有显著性差异；而照射组大鼠开始虽有增加的趋势,但比较缓慢,照射2周后,明显低于非照射组的上升幅度。非照射组大鼠海马中GABA含量逐渐减少,与对照组比较具有显著性差异,而照射组大鼠开始虽有减少的趋势,但比较缓慢,照射2周后,明显低于非照射组的下降幅度。说明低剂量伽玛刀照射控制癫痫发作与海马中Glu、GABA的含量变化有关。由此可以认为伽玛刀低剂量照射能够通过调节海马中Glu与GABA的平衡以达到抗癫痫的作用。
Epilepsy is a set of clinical syndromes, which is characterized by transient disorder of cerebral function and caused by suddenly and recurrently seizure of neuron in brain, and there are a series of physiological and pathological changes including cerebral blood flow、metabolism、neurotransmitters and so on. It is the highest incidence of the disease in nervous system except of cerebrovascular diseases. The incidence rate is 0.5%-1.0%. Of which 25% were drug refractory epilepsy. It affects the normal life of patients seriously. There are about 9 million epileptic patients in our country. Epileptic patients and their families in social life, are under enormous psychological pressure. It has brought a heavy burden to a medicine, family and community.
So far, the mechanism of epilepsy has not been fully uncovered. Nevertheless Many experts of epilepsy have generally accepted that there are two important characters of epilepsy's:the increase of neuronal excitability and the firing of highly synchronization. Glutamate (Glu) is the major excitatory amino acid neurotransmitter in brain. More than 50% neurotransmitter of synapses is Glu. Almost the excitatory neurons are glutamatergic neurons. It is crucial that Glu maintains the normal excitability of neurons. However, excessive accumulation of Glu in the extracellular could lead to convulsion.γ-amino butyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system, and plays a crucial role in blocking the proliferation and transmission of excitement. Reduced synthesis of GABA may result in that excitement of neurons is out of control, leading to the onset of epilepsy.
At present, the main method of controlling epilepsy is to use chemicals. However, the mainly used anti-epileptic drugs (AEDs) can only control about 70 to 80 percent the seizure. While the side effects of AEDs accompanied with long term administration are serious. As the development of medical imaging technology and Electrophysiology, positioning of the epileptogenic focus has become more and more accurate, and surgical treatment has become an important means of intractable epilepsy. But the risk of surgery can not be avoided. In addition to regular neurosurgical craniotomy complications such as bleeding, infection, limb motor dysfunction, cranial nerve dysfunction, etc. Mental or emotional abnormalities, language dysfunction, mental and memory decline, etc, may also occur. The incidence is 0.5%～20.0%. It is necessary to explore a more effective and safe method of treatment.
Gamma Knife radio surgery is a minimally invasive, safe and accurate positioning treatment, and has the advantage of repeatability. In a small volume, concentrated, precise high-dose radiation will not cause damage on the surrounding brain tissue of target point, and a minor effect on nerve function. The safety and efficacy in animal experiments and clinical studies had already been reported. More importantly, patients with short hospital stay and quick recovery, low cost, and it will not affect their quality of life. Over the past 10 years, the application of low-dose exposure to epilepsy was gradually increased. Most scholars believe that the dose of 10Gy irradiation does not produce a small area of brain necrosis. Seizures can be controlled without complications. To further study the anti-epilepsy of low-dose irradiation and to explore whether the anti-epilepsy of low-dose irradiation is obtained by regulating the excitatory and inhibitory neurotransmitter, the effect of low-dose irradiation on Glu and GABA in hippocampus of epileptic rats induced by li-pilocapine.Then discuss the antiepileptic mechanism of low-dose irradiation in the level of the neurotransmitter, to provide a theoretical basis for Gamma Knife treatment of epilepsy.
105 healthy adult male Wistar rats of SPF level were randomly divided into two groups namely, the control group (25), model group (80). With intraperitoneal injection of saline control group, model group were treated with intraperitoneal injection of lithium chloride solution (127mg/kg) and pilocarpine (30mg/kg). The successful established 50 epileptic rats were randomly divided into two groups, namely, irradiation group (25), non-irradiation group (25). The control group, irradiated and non-irradiated group were individually randomly divided into five different groups, namely,1 day after Gamma Knife irradiation group,1-week group, 2 weeks,4 weeks group,8-week group, each group 5.
After the success of modeling, observing a period of time, when repeated seizures occur, under anesthesia the irradiated rats were fixed in location-specific gamma knife rack, Coronal magnetic resonance imaging of brain continuous scanning to determine the radiation target volume (left hippocampus) of three-dimensional coordinates. Then carry out the gamma knife irradiation scheme, using 4 mm collimator, peripheral dose of 20 Gy, and so dose curve 80%, the center dose of 25Gy.
At the corresponding time points (gamma knife irradiation 1 day,1 week,2 weeks,4 weeks,8 weeks), obtained hippocampus by craniotomy under anesthesia, weighing, preparation of homogenate, add the serine, methanol in succession, and respectively centrifugating about 5min with 10000 r/min, 100μL supernatant was taken into liquid chromatography to test.
Model group:55 of 80 rats occurs above gradeⅣ(the Racine classification standard) seizures at modeling, after1 week occurred repeated seizures, and gradually achieve the Racine classification standardⅢand above, included in this study.2 weeks after irradiation, the degree of seizures comes down gradually toⅡ-Ⅲdegree in irradiated group; 4 weeks after irradiation, toⅠ-Ⅱdegree. In non-irradiated group, seizure has always been in gradeⅢor above.
2 weeks after irradiation, the content of Glu in the hippocampus of the rats in non-irradiated group and irradiated group were higher significantly compared with control group, that of radiation group was lower significantly compared with non-irradiated group (P<0.05). Meanwhile the content of GABA in the hippocampus of the rats in non-irradiated group and irradiated group were lower significantly compared with control group, that of radiation group was higher significantly compared with non-irradiated group (P<0.05).
4 and 8 weeks after irradiation, the content of Glu was decreasing and the content of GABA was rising in the hippocampus of the rats irradiated group,, being significantly difference compared with the control group and non-irradiated group (P<0.05).
1. We investigated the anti-epileptic effect of gamma knife irradiation using the epileptic rat model and discovered that low doses of gamma knife irradiation can reduce the degree of epileptic seizures in rats, and no rat died of serious complications because of the gamma knife irradiation, and further illustrate the safety and effectiveness of low-dose radiation for epilepsy.
2. The content of Glu in the hippocampus of the rats in non-irradiated group increased significantly compared with control group. The content of Glu in the hippocampus of irradiated rats has the increasing trend started, but relatively slow;2 weeks after irradiation, that was lower significantly compared with non-irradiated group (P<0.05). The content of GABA in the hippocampus of the rats in non-irradiated group decreased significantly compared with control group. The content of GABA in the hippocampus of irradiated rats has the decreasing trend started, but relatively slow;2 weeks after irradiation, that was higher significantly compared with non-irradiated group (P<0.05). Note low-dose gamma knife irradiation in controlling seizures, it is also affect the content of Glu, GABA in hippocampus.
We can conclude that low-dose gamma knife irradiation can regulate the balance of Glu and GABA in hippocampus to achieve anti-epileptic effect.
癫痫的发病机制到目前为止仍然没有明确,但癫痫发作的两个重要特征是神经元兴奋性增高和高度同步化放电,这已得到多数学者的认同。谷氨酸(Glutamate, Glu)是脑内最主要的兴奋性氨基酸类递质。脑内超过50%的突触以Glu为递质。几乎所有的兴奋性神经元均是谷氨酸能神经元。Glu对于维持神经元的正常兴奋性有着至关重要的作用。然而过多的Glu聚集在细胞外则可能导致惊厥。γ-氨基丁酸(γ-amino butyric acid, GABA)是中枢神经系统最重要的抑制性神经递质,在阻断兴奋的扩散及传导过程中起决定性作用。GABA的合成减少,可使神经元的兴奋得不到正常控制,导致癫痫的发作。
目前癫痫发作的控制仍以长期服药为主,常用的一线抗癫痫药(AEDs)可以使70%-80%的癫痫发作得以控制,但长期用药也会给患者带来严重的不良反应,并且仍有20%-25%的癫痫是药物难治性的。随着医学影像技术和脑电生理技术的发展,对致痫灶定位已越来越准确,采用外科手术治疗难治性癫痫已成为癫痫治疗的一种重要手段。但手术的风险性是无法避免的,除了常规神经外科开颅手术的并发症如出血、感染、肢体运动功能障碍、颅神经功能障碍等,还可见精神情绪异常、语言功能障碍、智力和记忆力下降等,发生率为0.5%-20.0%。这就需要探索更安全、有效的治疗方法。
伽玛刀放射外科手术是一种微创、安全、定位准确的治疗手段,且具有可重复性的优点。可以在很小的容积内集中、精确的进行照射,对周边脑组织不造成损伤,对神经功能的影响轻微。伽玛刀放射外科治疗癫痫的安全性、有效性在动物实验和临床研究中早有报道。更重要的是,在伽玛刀治疗后,患者住院时间短,恢复快,费用低,不会影响其生活质量。近10年来,应用伽玛刀低剂量照射治疗癫痫的报告逐渐增多,多数学者认为10Gy的剂量小范围照射不产生脑坏死灶,可控制癫痫发作,安全、无并发症。为了进一步研究伽玛刀低剂量照射的抗癫痫作用及探讨其是否通过调节兴奋性神经递质和抑制性神经递质的平衡发挥抗癫痫作用,本实验采用氯化锂-匹罗卡品(Li-Pilo)癫痫大鼠模型进行研究伽玛刀低剂量照射对致痫大鼠海马中Glu、GABA的影响,从而在神经递质水平讨论伽玛刀的抗癫痫机制,为伽玛刀治疗癫痫提供理论依据。
将105只SPF级健康成年雄性Wistar大鼠随机分为两组即对照组(25只)、模型组(80只)。对照组采用腹腔注射生理盐水,模型组采用腹腔注射氯化锂溶液(127mg/kg)和匹罗卡品(30mg/kg)。将成功建立的50只癫痫大鼠模型再随机分为两组,即照射组(25只)、非照射组(25只)。对照组、照射组、非照射组各随机分为5个小组,即伽玛刀照射后1天组、1周组、2周组、4周组、8周组,每小组5只。
造模成功后,观察一段时间,大鼠模型出现反复的癫痫发作后,在麻醉状态下将照射组大鼠固定于大鼠专用的伽玛刀定位架上,进行脑冠状位磁共振成像连续扫描,确定照射靶区(左侧海马)三维坐标。然后实施伽玛刀照射,采用4 mm准直器,设一个靶点,周边剂量20 Gy,等剂量曲线80%,中心剂量25Gy。
在相应时间点(伽玛刀照射后1天、1周、2周、4周、8周),麻醉状态下开颅取海马组织,称重,制备匀浆液,先后加内标高丝氨酸、甲醇分别按10000 r/min,离心5min,取100μL上清液于液相色谱样品瓶中进行检测。
模型组大鼠：80只大鼠有55只大鼠造模时均出现Racine分级标准Ⅳ级以上的癫痫发作,1周后出现反复的癫痫发作,并逐渐达到Racine分级标准Ⅲ级以上,为了组间的均衡性,随机剔除5只,有50只纳入本研究对象。经过伽玛刀照射2周后,照射组大鼠癫痫发作程度逐渐减轻,降为Ⅱ-Ⅲ级；伽玛刀照射4周后,发作程度为Ⅰ-Ⅱ级；而非照射组大鼠癫痫发作程度始终在Ⅲ级以上。
伽玛刀照射后第2周,照射组和非照射组大鼠海马中Glu含量均高于对照组,照射组低于非照射组,差异具有统计学意义(P<0.05)；照射组和非照射组GABA含量均低于对照组,照射组高于非照射组,差异具有统计学意义(P<0.05)。
伽玛刀照射后第4、8周,照射组海马中Glu呈降低趋势、GABA呈上升趋势,与非照射组、对照组比较差异均有统计学意义(P<0.05)。
1、本研究通过实验性癫痫大鼠模型研究伽玛刀低剂量照射的抗癫痫效应,发现伽玛刀低剂量照射不仅可以减轻癫痫大鼠的发作程度,而且没有发生因为伽玛刀照射引起的严重并发症导致大鼠死亡,进一步说明了伽玛刀低剂量照射治疗癫痫的安全性、有效性。
2、非照射组大鼠海马中Glu含量逐渐增加,与对照组比较具有显著性差异；而照射组大鼠开始虽有增加的趋势,但比较缓慢,照射2周后,明显低于非照射组的上升幅度。非照射组大鼠海马中GABA含量逐渐减少,与对照组比较具有显著性差异,而照射组大鼠开始虽有减少的趋势,但比较缓慢,照射2周后,明显低于非照射组的下降幅度。说明低剂量伽玛刀照射控制癫痫发作与海马中Glu、GABA的含量变化有关。由此可以认为伽玛刀低剂量照射能够通过调节海马中Glu与GABA的平衡以达到抗癫痫的作用。
Epilepsy is a set of clinical syndromes, which is characterized by transient disorder of cerebral function and caused by suddenly and recurrently seizure of neuron in brain, and there are a series of physiological and pathological changes including cerebral blood flow、metabolism、neurotransmitters and so on. It is the highest incidence of the disease in nervous system except of cerebrovascular diseases. The incidence rate is 0.5%-1.0%. Of which 25% were drug refractory epilepsy. It affects the normal life of patients seriously. There are about 9 million epileptic patients in our country. Epileptic patients and their families in social life, are under enormous psychological pressure. It has brought a heavy burden to a medicine, family and community.
So far, the mechanism of epilepsy has not been fully uncovered. Nevertheless Many experts of epilepsy have generally accepted that there are two important characters of epilepsy's:the increase of neuronal excitability and the firing of highly synchronization. Glutamate (Glu) is the major excitatory amino acid neurotransmitter in brain. More than 50% neurotransmitter of synapses is Glu. Almost the excitatory neurons are glutamatergic neurons. It is crucial that Glu maintains the normal excitability of neurons. However, excessive accumulation of Glu in the extracellular could lead to convulsion.γ-amino butyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system, and plays a crucial role in blocking the proliferation and transmission of excitement. Reduced synthesis of GABA may result in that excitement of neurons is out of control, leading to the onset of epilepsy.
At present, the main method of controlling epilepsy is to use chemicals. However, the mainly used anti-epileptic drugs (AEDs) can only control about 70 to 80 percent the seizure. While the side effects of AEDs accompanied with long term administration are serious. As the development of medical imaging technology and Electrophysiology, positioning of the epileptogenic focus has become more and more accurate, and surgical treatment has become an important means of intractable epilepsy. But the risk of surgery can not be avoided. In addition to regular neurosurgical craniotomy complications such as bleeding, infection, limb motor dysfunction, cranial nerve dysfunction, etc. Mental or emotional abnormalities, language dysfunction, mental and memory decline, etc, may also occur. The incidence is 0.5%～20.0%. It is necessary to explore a more effective and safe method of treatment.
Gamma Knife radio surgery is a minimally invasive, safe and accurate positioning treatment, and has the advantage of repeatability. In a small volume, concentrated, precise high-dose radiation will not cause damage on the surrounding brain tissue of target point, and a minor effect on nerve function. The safety and efficacy in animal experiments and clinical studies had already been reported. More importantly, patients with short hospital stay and quick recovery, low cost, and it will not affect their quality of life. Over the past 10 years, the application of low-dose exposure to epilepsy was gradually increased. Most scholars believe that the dose of 10Gy irradiation does not produce a small area of brain necrosis. Seizures can be controlled without complications. To further study the anti-epilepsy of low-dose irradiation and to explore whether the anti-epilepsy of low-dose irradiation is obtained by regulating the excitatory and inhibitory neurotransmitter, the effect of low-dose irradiation on Glu and GABA in hippocampus of epileptic rats induced by li-pilocapine.Then discuss the antiepileptic mechanism of low-dose irradiation in the level of the neurotransmitter, to provide a theoretical basis for Gamma Knife treatment of epilepsy.
105 healthy adult male Wistar rats of SPF level were randomly divided into two groups namely, the control group (25), model group (80). With intraperitoneal injection of saline control group, model group were treated with intraperitoneal injection of lithium chloride solution (127mg/kg) and pilocarpine (30mg/kg). The successful established 50 epileptic rats were randomly divided into two groups, namely, irradiation group (25), non-irradiation group (25). The control group, irradiated and non-irradiated group were individually randomly divided into five different groups, namely,1 day after Gamma Knife irradiation group,1-week group, 2 weeks,4 weeks group,8-week group, each group 5.
After the success of modeling, observing a period of time, when repeated seizures occur, under anesthesia the irradiated rats were fixed in location-specific gamma knife rack, Coronal magnetic resonance imaging of brain continuous scanning to determine the radiation target volume (left hippocampus) of three-dimensional coordinates. Then carry out the gamma knife irradiation scheme, using 4 mm collimator, peripheral dose of 20 Gy, and so dose curve 80%, the center dose of 25Gy.
At the corresponding time points (gamma knife irradiation 1 day,1 week,2 weeks,4 weeks,8 weeks), obtained hippocampus by craniotomy under anesthesia, weighing, preparation of homogenate, add the serine, methanol in succession, and respectively centrifugating about 5min with 10000 r/min, 100μL supernatant was taken into liquid chromatography to test.
Model group:55 of 80 rats occurs above gradeⅣ(the Racine classification standard) seizures at modeling, after1 week occurred repeated seizures, and gradually achieve the Racine classification standardⅢand above, included in this study.2 weeks after irradiation, the degree of seizures comes down gradually toⅡ-Ⅲdegree in irradiated group; 4 weeks after irradiation, toⅠ-Ⅱdegree. In non-irradiated group, seizure has always been in gradeⅢor above.
2 weeks after irradiation, the content of Glu in the hippocampus of the rats in non-irradiated group and irradiated group were higher significantly compared with control group, that of radiation group was lower significantly compared with non-irradiated group (P<0.05). Meanwhile the content of GABA in the hippocampus of the rats in non-irradiated group and irradiated group were lower significantly compared with control group, that of radiation group was higher significantly compared with non-irradiated group (P<0.05).
4 and 8 weeks after irradiation, the content of Glu was decreasing and the content of GABA was rising in the hippocampus of the rats irradiated group,, being significantly difference compared with the control group and non-irradiated group (P<0.05).
1. We investigated the anti-epileptic effect of gamma knife irradiation using the epileptic rat model and discovered that low doses of gamma knife irradiation can reduce the degree of epileptic seizures in rats, and no rat died of serious complications because of the gamma knife irradiation, and further illustrate the safety and effectiveness of low-dose radiation for epilepsy.
2. The content of Glu in the hippocampus of the rats in non-irradiated group increased significantly compared with control group. The content of Glu in the hippocampus of irradiated rats has the increasing trend started, but relatively slow;2 weeks after irradiation, that was lower significantly compared with non-irradiated group (P<0.05). The content of GABA in the hippocampus of the rats in non-irradiated group decreased significantly compared with control group. The content of GABA in the hippocampus of irradiated rats has the decreasing trend started, but relatively slow;2 weeks after irradiation, that was higher significantly compared with non-irradiated group (P<0.05). Note low-dose gamma knife irradiation in controlling seizures, it is also affect the content of Glu, GABA in hippocampus.
We can conclude that low-dose gamma knife irradiation can regulate the balance of Glu and GABA in hippocampus to achieve anti-epileptic effect.
引文
[1]Racine RJ. Modification of seizure activity by electrical stimulation Ⅱ Motor seizure [J]. Electroencephalogr Clin Neurophysiol,1972,32(3):281-294.
[2]Scharfman H E. The neurobiology of epilepsy [J]. Curr Neurol Neurosci Rep, 2007,7 (4):348-354.
[3]Berg A T. Defining intractable epilepsy [J]. Adv Neurol,2006,97:5-10.
[4]Suzanne C, Wilke W.Mechanisms of epileptigenesis and the expression of Epileptiform activity [M]. In:Elaine Wyllie. The treatment of epilepsy:principles and practice,2nd ed Baltimore:Williams and Wilkins 1997,53-77
[5]Racine R J. Modification of seizure activity by electrical stimulation Ⅱ motor seizure [J]. Electroencephogr Clin Neurophysiol,1972,32 (3):781-794.
[6]Klitgaard H, Matagne A, Vanneste Goemaere J, et al. Pilocarpine-induced Epileptogenesis in the rat:impact of initialduration of status epileptic us on electrophysiological and neuropathological alterations [J]. Epilepsy Res,2002,51 (12):93-107.
[7]Proper E A, Jansen G H, van Veelen C W, et al. A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sp routing [J]. Acta Neuropathol,2001,101 (4):405-409.
[8]Kreak P, MikudeckaA, Druge R, et all An animal model of no convulsive status epilepticus:a contribution to clinical controversies [J] 1Epilepsia,2001,42(2): 171-180.
[9]Morimoto K, Fahnestock M, Racine RJ1 Kindling and status epilepticus models of epilepsy:rewiring the brain [J]. ProgNeurobiol,2004,73 (1):1260.
[10]李国良,肖波,谢光洁,等.匹罗卡品颞叶癫痫大鼠模型[J].湖南医科大学学报,2003,28(1)：29-32.
[11]高旭光,吕晓明,刘芳.幼鼠早期癫痫持续状态对海马结构损伤的远期影响[J].中国神经免疫学和神经病学杂志,2004,1(10)：22-25.
[12]Schmidt R, Humpel C, Wetmore C, et al. Cellular hybridization for BD-NF, trkB, and NGF mRNAs and BDNF-immunoreactivity in rat forebrain after pilocarpine-induced status epilepticus [J]. Exp Brain Res,1996,107 (20):3312347.
[13]Bamford J, Sandercock P, Dennis M, et al. Classification and natural history of clinically indentifiable subtypes of cerebral infarction. Lancet,1991, 337 (8756):152121526.
[14]高旭光,冯体良,王军.氯化锂-匹罗卡品致大鼠急性癫痫模型[J].中国血液流变学杂志,2003,13(4)：308-312.
[15]许峰,朱遂强,唐洲平,等.氯化锂预处理时间的改变对锂-匹鲁卡品诱导大鼠痫性发作的影响.卒中与神经疾病[J],2005,12(4)：230-235.
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[2]Scharfman H E. The neurobiology of epilepsy [J]. Curr Neurol Neurosci Rep, 2007,7 (4):348-354.
[3]Berg A T. Defining intractable epilepsy [J]. Adv Neurol,2006,97:5-10.
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[6]Klitgaard H, Matagne A, Vanneste Goemaere J, et al. Pilocarpine-induced Epileptogenesis in the rat:impact of initialduration of status epileptic us on electrophysiological and neuropathological alterations [J]. Epilepsy Res,2002,51 (12):93-107.
[7]Proper E A, Jansen G H, van Veelen C W, et al. A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sp routing [J]. Acta Neuropathol,2001,101 (4):405-409.
[8]Kreak P, MikudeckaA, Druge R, et all An animal model of no convulsive status epilepticus:a contribution to clinical controversies [J] 1Epilepsia,2001,42(2): 171-180.
[9]Morimoto K, Fahnestock M, Racine RJ1 Kindling and status epilepticus models of epilepsy:rewiring the brain [J]. ProgNeurobiol,2004,73 (1):1260.
[10]李国良,肖波,谢光洁,等.匹罗卡品颞叶癫痫大鼠模型[J].湖南医科大学学报,2003,28(1)：29-32.
[11]高旭光,吕晓明,刘芳.幼鼠早期癫痫持续状态对海马结构损伤的远期影响[J].中国神经免疫学和神经病学杂志,2004,1(10)：22-25.
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[13]Bamford J, Sandercock P, Dennis M, et al. Classification and natural history of clinically indentifiable subtypes of cerebral infarction. Lancet,1991, 337 (8756):152121526.
[14]高旭光,冯体良,王军.氯化锂-匹罗卡品致大鼠急性癫痫模型[J].中国血液流变学杂志,2003,13(4)：308-312.
[15]许峰,朱遂强,唐洲平,等.氯化锂预处理时间的改变对锂-匹鲁卡品诱导大鼠痫性发作的影响.卒中与神经疾病[J],2005,12(4)：230-235.
[1]崔世民,刘梅丽,靳松,等.脑MRI局部解剖与功能图谱[M].北京：人民卫生出版社,2007：71276.
[2]谭启富,吴承远,李龄,等.癫痫外科学[M].北京：人民卫生出版社,2006.4.
[3]史保中,程小兵,孟秀芝,等.顽固性癫痫致痫灶的综合定位和外科治疗[J].陕 西医学杂志,2007,36(1)：49-52.
[4]Engel J Jr, PampudiV. J. Srimm, Theodoros Topalidis, et al. Early versus late surgery for intractable seizures [J]. Adv ExpMed Biol,2002,49 (7):99-105.
[5]Talairach J, Bancand J:zikla G, et al. Approche nouvelle de la neuro chirurgie del'epilepsie:Methodologie stereotaxique etresultats therapeutiques. Neurochirurgie (Suppl 1).
[6]Malis L I, Rose J E, Kruger L, et al. Production of laminar lesions in the cerebral cortex by deuteron irradiation. In:Haley Tj SniderRs (eds). Response of the nervous system to ionizing radiation. New York:Academic Press,1962:359-368.
[7]Elomaa E. Focal irradiation of the brain:an alternation to temporal lobe resection in intractable focal epilepsy. Med Hypoheses,1980; 6:501.
[8]Barcia2Salorio JL, Gerda M, Ciudad J, et al.Reponse of experimental epileptis focus to focalionizing radiation. Appl Neurophysiol,1987;50:359.
[9]Barcia2Salorio JL, Roldan P, Henandez G, etal. Radiosurgical treatment of epilepsy. Appl Neurophysiol,1985; 48:400.
[10]Heikkinen ER, Melnikowl KB. Relief of epilepsy by radiosurgery of cerebral arteriovenous malformations stereotact. Funct Neurosurg,1989; 53:157.
[11]Lunsford LD. Stereotatic radiosurgery of intracranial arteriovenous malformations in wikins RH Rengachary ss (eds):Nerusourgery update.New York: McGraw Hill,1990:175-185.
[12]Lindquist C, Kihlstrom L, Hell Strand E.Functional neurosurgery:A future for the Gamma Knife? Stereotact Funct Neurosurg,1991; 57:72.
[13]Gerszten PC. Adelson PD, Kondziolka D, etal. Seizure out come in children. Treated for arteriovenous. Malformations using Gammaknife radiosurgery. Pediatr Neurosurg,1996; 24 (3):139.
[14]Barcia JA, Barcia2salorio J, Lopez2Gomez L, et al. Stereotatic radiosurgery may be effective in the treatment of Idiopathic epilepsy:Reporton the methods and results in a series of elevecases. Sterotact Funct Neurosurg,1994; 63:271.
[15]Heikkinen ER, Heikkinen MI, Sotaniem K.Stereotatic Radio2therapy instead of conventional epilepsy surgery:A case report. Acta Neuro chir (wien),1992; 119 159.
[16]Barcia-Salorio JL, Barcia JA, Roldan P, et al. Radiosurgery of epilepsy. Acta Neurochir Supp 1 (Wien),1993,58:195-197.
[17]Barbaro NM, Quigg M, Broshek DK, et al. A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy:seizure response, adverse events, and verbal memory [J].2009,65(2):167-75.
[18]Regis J, ReyM, Bartolomei F, et al. Gamma knife surgery in mesial temporal lobe epilepsy:a p prospective multicenter study. Epilepsia,2004,45(5):504-515.
[19]Elomaa E. Focal irradiation of the brain:an alternation to temporal lobe resection in intractable focal epilepsy. Med Hypoheses,1980; 6:501.
[20]Barcia-Salorio JL, Gerda M, Ciudad J, et al.Reponse of experimental epileptis focus to focal ionizing radiation. Appl Neurophysiol,1987;50:359.
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