伽玛刀照射对致痫大鼠脑脊液中谷氨酸及γ-氨基丁酸的影响
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摘要
第一章锂—匹罗卡品诱导实验性颞叶癫痫大鼠模型的建立及致痫大鼠早期死亡原因分析
[目的]
研究锂—匹罗卡品颞叶癫痫模型致痫后痫性发作的行为学特点、脑电图变化及致痫大鼠早期死亡原因,从而为建立稳定的锂—匹罗卡品颞叶癫痫模型提供方法及降低致痫大鼠早期死亡率。
[方法]
将Wistar大鼠采用完全随机分组方法分为生理盐水对照组25只、癫痫模型组80只,癫痫模型组大鼠依次给予氯化锂、硫酸阿托品、匹罗卡品腹腔注射诱发癫痫持续状态(status epilepticus, SE),持续1h后注射地西泮终止发作。其后每天观察其自发性痫性发作(spontaneous recurrent seizures, SRS),于造模前清醒状态、SE当时及SE6W分别对大鼠进行EEG描记。并记录致痫大鼠于SE期、静默期、慢性期死亡情况。
[结果]
锂—匹罗卡品颞叶癫痫模型组大鼠SE诱发成功率92.5%(74/80)。经过10-20天的静默期后,可观察到Ⅰ-Ⅴ级的反复SRS, EEG在急性期表现为持续丛集性高波幅棘波；慢性期可描记到散发棘波或棘慢波。致痫大鼠于SE期、静默期、慢性期死亡率分别为为21.62%(16/74)、4.06%(3/74)、0%。总死亡率为25.68%(19/74),癫痫模型成功率为68.8%(55/80)。
[结论]
锂-匹罗卡品颞叶癫痫模型致痫成功率高,致痫后总体死亡率不高,且主要集中于SE期,是一种理想的颞叶癫痫动物模型。
第二章伽玛刀照射对颞叶癫痫大鼠脑脊液中谷氨酸及γ-氨基丁酸的影响
[目的]
研究伽玛刀对颞叶癫痫大鼠脑脊液中谷氨酸及γ-氨基丁酸含量的影响,探讨伽玛刀放射外科治疗颞叶癫痫的机理,为临床实践提供理论依据。
[方法]
将Wistar大鼠分为生理盐水对照组、手术组、非手术组,每组25只。建立锂—匹罗卡品颞叶癫痫模型,手术组大鼠SE后4周给予伽玛刀治疗,照射靶点为左侧海马,周边计量为20Gy,等剂量曲线为80%。分别于GKS前、GKS后1d、GKS后2W、GKS后4W、GKS后8W观测致痫大鼠癫痫发作频率,并分别于GKS后1d、GKS后1W、GKS后2W、GKS后4W、GKS后8W在枕骨大孔处穿刺采集脑脊液,用液相色谱联合质谱方法检测脑脊液中Glu、GABA含量。
[结果]
行为学观察发现生理盐水对照组大鼠无癫痫发作。致痫大鼠在伽玛刀照射后4W及8W,手术组大鼠癫痫发作次数显著少于非手术组大鼠癫痫发作次数(P=0.000),而伽玛刀照射后1d、2W手术组大鼠癫痫发作次数与非手术组大鼠癫痫发作次数无显著差异(P>0.05)。脑脊液检查结果示伽玛刀照射致痫大鼠1W后手术组大鼠脑脊液中Glu含量显著低于非手术组大鼠脑脊液中Glu含量(P<0.05),且2W后、4W后、8W后之间也存在显著差异(P=0.000),手术组Glu含量(X=709.579nmol/ml)低于非手术组Glu含量(X=828.620nmol/ml),且手术组大鼠脑脊液中Glu含量随时间延长而减少。照射1W后手术组GABA含量显著高于非手术组大鼠含量出现明显差异(P<0.05),且2W后、4W后、8W后之间也存在显著差异(P=0.000),手术组GABA含量(X=221.866nmol/ml)高于非手术组GABA含量(X=159.730nmol/ml),且手术组大鼠脑脊液中GABA含量随时间延长而增加。
[结论]
伽玛刀照射致痫大鼠后致痫大鼠脑脊液中Glu含量降低、GABA含量升高先于致痫大鼠癫痫发作频率降低,致痫大鼠中Glu含量降低、GABA含量升高,导致兴奋性神经递质与抑制性神经递质失衡,从而降低致痫大鼠癫痫发作频率。致兴奋性神经递质与抑制性神经递质失衡可能是伽玛刀治疗颞叶癫痫的重要机制之一。
Establish the lithium-pilocarpine-induced experimental rat model of temporal lobe epilepsy and analysis the early death of induced epileptic rats
OBJECTIVE
Study of the behavioral seizure characteristics, EEG changes and epileptic causes of early death in rats that were lithium-pilocarpine model of temporal lobe epilepsy after epileptic seizures, So as to provide a way and to reduce early mortality of epileptic rats for establishing a stable lithium-pilocarpine model of temporal lobe epilepsy.
METHODS
The Wistar rats were randomly divided into saline control group which contains 25 rats, and epilepsy model group which contains 80, Epilepsy model rats were given lithium chloride, atropine sulfate, pilocarpine by intraperitoneal injection to induce status epilepticus(SE), and to terminate seizures by diazepam 1 hour after the injection of continuous. To observe the spontaneous recurrent seizures(SRS) per day thereafter, and record the EEG trace of the rats at awaking before making model, being status epilepticus, six weeks later. So as to record the deaths of epileptic rats in the SE period, quiet period, and chronic phase.
RESULTS
The success rate of SE-induced was 92.5%(74/80) in lithium-pilocarpine model of temporal lobe epilepsy rats. After 10-20 days of the silent period, we can observe I-V grade repeated SRS, EEG in the acute phase showed sustained high volatility spikes clustered; and we can record the dissemination of spikes or spike and slow wave in chronic phase. The mortality of induced epileptic rats was 21.62% in SE period,4.06% in silent period,0% in chronic phase. Total mortality rate was 25.68% (19/74). The success rate of epilepsy model was 68.8%(55/80)
CONCLUSION
Lithium-pilocarpine model of temporal lobe epilepsy epileptic high success rate, After epilepsy induced, the overall mortality rate of epileptic is not high, and is mainly focused on the SE period, is an ideal animal model of temporal lobe epilepsy.
Chapter Two
The effection of glutamate and y-aminobutyric acid in cerebrospinal fluid of rats with temporal lobe epilepsy by low-dose gamma knife irradiation
Objective
Research the effection of glutamate and y-aminobutyric acid in cerebrospinal fluid of rats with temporal lobe epilepsy by gamma knife, To investigate the mechanism of Gamma Knife radiosurgery treatment of temporal lobe epilepsy, To provide a theoretical basis for clinical practice.
Method
The Wistar rats were divided into saline control group, surgery group, non-surgical group, each 25 rats, To establish a temporal lobe epilepsy model with lithium-pilocarpine, SE-operated rats were given Gamma Knife after 4 weeks, Irradiated target was the left hippocampus, Out Measurement was20Gy, Isodose curve was 80%, To observe the frequency of epileptic seizures in rats at GKS before, GKS after Id, GKS after 2W, GKS after 4W, GKS post-8W respectively, then puncture and collect the CSF at the foramen at GKS after 1d, GKS after 1W, GKS after 2W, GKS after 4W, GKS post-8W respectively, Detect the Glu,GABA content in CSF by joint mass spectrometry Liquid Chromatography.
Results
Behavioral obseevation found the saline control rats without epileptic seizures. After gamma knife irradiation 4W,the number of epileptic seizures in rats of operation group were significantly different from non-surgical group(P=0.000),The seizure frequency in rats with Gamma Knife irradiation 1d,2W later were no significant difference from non-surgical rats(P> 0.05), The cerebrospinal fluid examination results showed that the Glu content in cerebrospinal fluid of operated rats were significant differences from non-operated group after Gamma irradiation induced epileptic rats 1W(P<0.05), and there were difference 2W later,4W later,8W later. Operation group (Glu content of number 709.579nmol/ml) lower than that of non-operation group (Glu content of number 828.620nmol/ml). And the Glu content in cerebrospinal fluid of the surgical rats deceased with time. The GABA levels of the surgical group with 1W irradiation were significant different from non-operated rats(P <0.05), and there was a significant difference at 2W later,4W later,8W later(P= 0.000), Operation group (GABA content of number 221.866nmol/ml) were higher than non-operation group (GABA content of number 159.730nmol/ml)), CSF GABA levels of the operation group increased with time.
Conclusion
After gamma knife irradiation induced epileptic rats, the Glu content in cerebrospinal fluid of epileptic rats decreased, GABA content increased, that prior to the reduced frequency of epileptic seizures in rats. Glu content decreased, GABA content increased in epileptic rats, cause excitatory neurotransmitter and inhibitory neurotransmitter imbalances, Thereby the frequency of epileptic seizures in rats were reduced. The imbalances between excitatory neurotransmitter and inhibitory neurotransmitter may be one of an important mechanism for temporal lobe epilepsy by gamma Knife treatment.
[目的]
研究锂—匹罗卡品颞叶癫痫模型致痫后痫性发作的行为学特点、脑电图变化及致痫大鼠早期死亡原因,从而为建立稳定的锂—匹罗卡品颞叶癫痫模型提供方法及降低致痫大鼠早期死亡率。
[方法]
将Wistar大鼠采用完全随机分组方法分为生理盐水对照组25只、癫痫模型组80只,癫痫模型组大鼠依次给予氯化锂、硫酸阿托品、匹罗卡品腹腔注射诱发癫痫持续状态(status epilepticus, SE),持续1h后注射地西泮终止发作。其后每天观察其自发性痫性发作(spontaneous recurrent seizures, SRS),于造模前清醒状态、SE当时及SE6W分别对大鼠进行EEG描记。并记录致痫大鼠于SE期、静默期、慢性期死亡情况。
[结果]
锂—匹罗卡品颞叶癫痫模型组大鼠SE诱发成功率92.5%(74/80)。经过10-20天的静默期后,可观察到Ⅰ-Ⅴ级的反复SRS, EEG在急性期表现为持续丛集性高波幅棘波；慢性期可描记到散发棘波或棘慢波。致痫大鼠于SE期、静默期、慢性期死亡率分别为为21.62%(16/74)、4.06%(3/74)、0%。总死亡率为25.68%(19/74),癫痫模型成功率为68.8%(55/80)。
[结论]
锂-匹罗卡品颞叶癫痫模型致痫成功率高,致痫后总体死亡率不高,且主要集中于SE期,是一种理想的颞叶癫痫动物模型。
第二章伽玛刀照射对颞叶癫痫大鼠脑脊液中谷氨酸及γ-氨基丁酸的影响
[目的]
研究伽玛刀对颞叶癫痫大鼠脑脊液中谷氨酸及γ-氨基丁酸含量的影响,探讨伽玛刀放射外科治疗颞叶癫痫的机理,为临床实践提供理论依据。
[方法]
将Wistar大鼠分为生理盐水对照组、手术组、非手术组,每组25只。建立锂—匹罗卡品颞叶癫痫模型,手术组大鼠SE后4周给予伽玛刀治疗,照射靶点为左侧海马,周边计量为20Gy,等剂量曲线为80%。分别于GKS前、GKS后1d、GKS后2W、GKS后4W、GKS后8W观测致痫大鼠癫痫发作频率,并分别于GKS后1d、GKS后1W、GKS后2W、GKS后4W、GKS后8W在枕骨大孔处穿刺采集脑脊液,用液相色谱联合质谱方法检测脑脊液中Glu、GABA含量。
[结果]
行为学观察发现生理盐水对照组大鼠无癫痫发作。致痫大鼠在伽玛刀照射后4W及8W,手术组大鼠癫痫发作次数显著少于非手术组大鼠癫痫发作次数(P=0.000),而伽玛刀照射后1d、2W手术组大鼠癫痫发作次数与非手术组大鼠癫痫发作次数无显著差异(P>0.05)。脑脊液检查结果示伽玛刀照射致痫大鼠1W后手术组大鼠脑脊液中Glu含量显著低于非手术组大鼠脑脊液中Glu含量(P<0.05),且2W后、4W后、8W后之间也存在显著差异(P=0.000),手术组Glu含量(X=709.579nmol/ml)低于非手术组Glu含量(X=828.620nmol/ml),且手术组大鼠脑脊液中Glu含量随时间延长而减少。照射1W后手术组GABA含量显著高于非手术组大鼠含量出现明显差异(P<0.05),且2W后、4W后、8W后之间也存在显著差异(P=0.000),手术组GABA含量(X=221.866nmol/ml)高于非手术组GABA含量(X=159.730nmol/ml),且手术组大鼠脑脊液中GABA含量随时间延长而增加。
[结论]
伽玛刀照射致痫大鼠后致痫大鼠脑脊液中Glu含量降低、GABA含量升高先于致痫大鼠癫痫发作频率降低,致痫大鼠中Glu含量降低、GABA含量升高,导致兴奋性神经递质与抑制性神经递质失衡,从而降低致痫大鼠癫痫发作频率。致兴奋性神经递质与抑制性神经递质失衡可能是伽玛刀治疗颞叶癫痫的重要机制之一。
Establish the lithium-pilocarpine-induced experimental rat model of temporal lobe epilepsy and analysis the early death of induced epileptic rats
OBJECTIVE
Study of the behavioral seizure characteristics, EEG changes and epileptic causes of early death in rats that were lithium-pilocarpine model of temporal lobe epilepsy after epileptic seizures, So as to provide a way and to reduce early mortality of epileptic rats for establishing a stable lithium-pilocarpine model of temporal lobe epilepsy.
METHODS
The Wistar rats were randomly divided into saline control group which contains 25 rats, and epilepsy model group which contains 80, Epilepsy model rats were given lithium chloride, atropine sulfate, pilocarpine by intraperitoneal injection to induce status epilepticus(SE), and to terminate seizures by diazepam 1 hour after the injection of continuous. To observe the spontaneous recurrent seizures(SRS) per day thereafter, and record the EEG trace of the rats at awaking before making model, being status epilepticus, six weeks later. So as to record the deaths of epileptic rats in the SE period, quiet period, and chronic phase.
RESULTS
The success rate of SE-induced was 92.5%(74/80) in lithium-pilocarpine model of temporal lobe epilepsy rats. After 10-20 days of the silent period, we can observe I-V grade repeated SRS, EEG in the acute phase showed sustained high volatility spikes clustered; and we can record the dissemination of spikes or spike and slow wave in chronic phase. The mortality of induced epileptic rats was 21.62% in SE period,4.06% in silent period,0% in chronic phase. Total mortality rate was 25.68% (19/74). The success rate of epilepsy model was 68.8%(55/80)
CONCLUSION
Lithium-pilocarpine model of temporal lobe epilepsy epileptic high success rate, After epilepsy induced, the overall mortality rate of epileptic is not high, and is mainly focused on the SE period, is an ideal animal model of temporal lobe epilepsy.
Chapter Two
The effection of glutamate and y-aminobutyric acid in cerebrospinal fluid of rats with temporal lobe epilepsy by low-dose gamma knife irradiation
Objective
Research the effection of glutamate and y-aminobutyric acid in cerebrospinal fluid of rats with temporal lobe epilepsy by gamma knife, To investigate the mechanism of Gamma Knife radiosurgery treatment of temporal lobe epilepsy, To provide a theoretical basis for clinical practice.
Method
The Wistar rats were divided into saline control group, surgery group, non-surgical group, each 25 rats, To establish a temporal lobe epilepsy model with lithium-pilocarpine, SE-operated rats were given Gamma Knife after 4 weeks, Irradiated target was the left hippocampus, Out Measurement was20Gy, Isodose curve was 80%, To observe the frequency of epileptic seizures in rats at GKS before, GKS after Id, GKS after 2W, GKS after 4W, GKS post-8W respectively, then puncture and collect the CSF at the foramen at GKS after 1d, GKS after 1W, GKS after 2W, GKS after 4W, GKS post-8W respectively, Detect the Glu,GABA content in CSF by joint mass spectrometry Liquid Chromatography.
Results
Behavioral obseevation found the saline control rats without epileptic seizures. After gamma knife irradiation 4W,the number of epileptic seizures in rats of operation group were significantly different from non-surgical group(P=0.000),The seizure frequency in rats with Gamma Knife irradiation 1d,2W later were no significant difference from non-surgical rats(P> 0.05), The cerebrospinal fluid examination results showed that the Glu content in cerebrospinal fluid of operated rats were significant differences from non-operated group after Gamma irradiation induced epileptic rats 1W(P<0.05), and there were difference 2W later,4W later,8W later. Operation group (Glu content of number 709.579nmol/ml) lower than that of non-operation group (Glu content of number 828.620nmol/ml). And the Glu content in cerebrospinal fluid of the surgical rats deceased with time. The GABA levels of the surgical group with 1W irradiation were significant different from non-operated rats(P <0.05), and there was a significant difference at 2W later,4W later,8W later(P= 0.000), Operation group (GABA content of number 221.866nmol/ml) were higher than non-operation group (GABA content of number 159.730nmol/ml)), CSF GABA levels of the operation group increased with time.
Conclusion
After gamma knife irradiation induced epileptic rats, the Glu content in cerebrospinal fluid of epileptic rats decreased, GABA content increased, that prior to the reduced frequency of epileptic seizures in rats. Glu content decreased, GABA content increased in epileptic rats, cause excitatory neurotransmitter and inhibitory neurotransmitter imbalances, Thereby the frequency of epileptic seizures in rats were reduced. The imbalances between excitatory neurotransmitter and inhibitory neurotransmitter may be one of an important mechanism for temporal lobe epilepsy by gamma Knife treatment.
引文
[1]Kreak P, MikudeckaA, Druge R, et all. An animalmodel of nonconvulsive status ep ilep ticus:a contribution to clinical controversies [J] Epilepsia,2001,42 (2):171-180.
[2]Morimoto K, FahnestockM, Racine RJ. Kindling and status epilepticus models of epilepsy:rewiring the brain[J]. ProgNeurobiol,2004,73 (1):1260-1269.
[3]伍犹梁,梁军潮,詹纯列,等.锂-匹罗卡品颞叶癫痫模型的建立及苔藓纤维出芽的动态变化[J].中国医学比较杂志,2009,19(6)：43-46.
[4]Racine RJ. Modification of seizure activity by electrical stimulation Ⅱ Motor seizure [J]. Electroencephalogr Clin Neurophysiol,1972,32(3):281-294.
[5]Glien M, Brandt C, Potschka H, et al. Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy[J]. Epilepsia, 2002,43 (4):350-357.
[6]Blanco MM, DosSantos Jr JG, Perez-Mendes P, Kohek SR, Cavarsan CF, Htlmmel M, Albuquerque C, Mello LE. Assessment of seizure susceptibility in pilocarpine epileptic and nonepileptic Wistar rats and of seizure reinduction with Pentylenetetrazole and electroshock models. EPilePsia.2008 Nov 19.[Epub ahead of print]
[7]Cavalheiro EA. The pilocarpine model of epilepsy[J].Ital J Neuro Sci,1995,16(12):33-38.
[8]Voutsinos-Porche B, Koning E, Kaplan H, et al.Temporal patterns of the cerebral inflammatory response in the rat lithium2pilocarpine model of temporal lobe epilepsy[J]. Neurobiol Dis,2004,17 (3):385-402.
[9]梁益,孙宏斌.氯化锂-匹罗卡品癫痫模型研究[J].实用医院临床杂志,2008,5(3)：112-115.
[10]中华人民共和国卫生部药典委员会编.临床用药须知.中华人民共和国药典.二部.北京：化学工业出版社,1996.38-42.
[1]Romanelli P, Anschel DJ. Radiosurgery for epilepsy[J]. LancetNeurol,2006,5 (7):613-620.
[2]Eder HG, Feichting M, Pieper T, et al. Gamma knife radiosurgery for callosotomy in children with drug-resistant epilepsy [J]. Childs Nerv Syst, 2006,22(8):1012-1017.
[3]梁军潮,徐波涛,杨红军,等.低剂量伽玛刀对致痫大鼠皮层及海马神经元Fos表达的影响[J].立体定向和功能性神经外科杂志,2006,19(1)：28-31.
[4]梁军潮,徐波涛,杨红军,等.小剂量伽玛刀对致痫大鼠脑神经元nNOS表达的影响[J].中国微侵袭神经外科杂志,2006,11(1)：24-26.
[5]Dillon WP, Barbaro N. Noninvasive surgery for epilepsy:the era of image guidanee[J]. AJNR Am J Neuroradiol,1999,20(2):185.
[6]Regis J, Peragui JC, Rey M, et al. First seleetive amygdalohippoeampal radiosurgery for'mesial temporal lobe epilepsy'[J]. Stereotaet Funct Neurosurg,1995,64(suppl 1):193-201.
[7]Regis J, Bartolomei F, Rey M, et al. Gamma knife surgery for mesial temporal lobe epilepsy[J]. Epilepsia,1999,40(1):1551-1556.
[8]Regis J, Rey M, Bartolomei F, et al. Gamma knife surgery in mesial temporal lobe epilepsy:a prospeetive multieenter study[J]. Epilepsia, 2004,45(5):504-515.
[9]Kawai K, Suzukil, Kurita H, et al. Failure of low-dose radiosurgery to control temporal lobe epilepsy[J]. J Neurosurg,2001,95(5):883 887.
[10]Sun B, DeSalles AA, Medin PM, et al. Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery [J]. Exp Neurol.1998 Dec;154(2):691-695.
[11]梁军潮,徐如祥,王伟民,等.低剂量伽玛刀照射癫痫大鼠脑神经元的超微结构研究[J].中国微侵袭神经外科杂志,2005；10(2)：83-85.
[12]Liscak R, Vladyka V, Novotny J Jr, et al.Leksell gamma knife lesioning of the rat hippocampus:the relationship between radiation dose and functional and structural damage[J].J Neurosurg.2002 Dec;97(5 Suppl):666-673.
[13]Regis J, Kerkerian-Legoff L, Rey M, et al. First biochemical evidence of differential functional effects following Gamma knife surgery[J]. Stereotact and functional neurosurgery 1996,66(suppl 1):29-38.
[14]Gerszten PC. Adelson PD, Kondziolka D, et al. Seizure out come in children. Treated for arteriovenous Malformations using Gamma knife radiosurgery[J]. Pediatr Neurosurg 1996,24(3):139-147.
[15]李学忠,包仕荛.谷氨酸和脑缺血[J].中国临床康复,2002,6(1)：137-138.
[4]柏干苹,方勇飞,李廷谦.谷氨酸在低氧性脑损伤中的作用[J].中国临床康复,2002,6(22)：3345-3346.
[16]Meldrum BS.Excitotoxicity and selective neuronal loss in epilepsy[J]. Brain Pathol 1993,3:405-412.
[17]Mattew J. D., Dennis DS. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain[J]. Lancet 1993,341:1607-1611.
[18]Sherwin. AL. Neuroactive amino acids in focally epileptic human brain:a review[J]. Neurochem-Res.1999,24:1387-1393.
[19]Moira KB, Whyte SJ, Hardwick LC, et al. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neurophils in vitro[J].J Clin Invest,1993,92:446-448.
[20]Sattler R, Tymianski M. Molecular mechanisms of glutamate receptor-mediated excitoxic neuronal cell death[J].Mol Neurobiol,2001,24(1-3):107-129.
[21]Joanna P, Zhenlin G, Xun W, et al. Group Ⅱ metabotropic glutamate receptors enhance NMDA receptor currents via a prote in kinase C-dependent mechanism in pyramidal neurons of rat prefrontal cortex [J]. J Phyisol,2004,554:765-777.
[22]Mohandas S, Mani J, Borgohain R, et al.Neuroprotection for acute ischemic stroke:An Overview[J]. Neurol India,2002,50(sl):s57-s63.
[23]Meguro R, LuJ, GavriloviciC, poulterMO. Static, transient and permanent organization of GABA receptor expression in calbindin-positive interneurons in response to amygdala kindle dseizures.Neurochemistry.2004,91(1)144-154.
[24]Simister RJ, McLean MA, Barker GJ, Duncan JS. Proton MR spectroscopy of metabolite concentrations intemporal lobe epilepsy and effect of temporal lobe resection.Epilepsy Re.2009,83(2-3):168-176.
[25]Bernard C, Cossart R, Hirsch JC, Esclapez M, Ben-Ari Y. What is GABAergic inhibition?How is it modified in epilepsy? Epilepsia.2000, 41 (suppl 6):890-595.
[1]Romanelli P, Anschel DJ. Radiosurgery for ep ilep sy[J]. LancetNeurol,2006,5 (7):613-620.
[2]Avanzini G, Franceschetti S. Cellular bi ol ogy of ep ilep t ogenesis[J]. Lancet Neurology,2003,2 (1):33-42.
[3]梁传栋,赵文清,李文玲,等.伽玛刀对大鼠皮层神经元钠电流的影响[J]. 中国神经精神疾病杂志,2008,34(4)：212-215.
[4]Bartol omei F, MassacrierA, ReyM, et al. Effect of gamma kniferadiosurgery on rat brain s odium channel subunit mRNA exp res-sion[J]. Stereotact Funct Neur osurg,1998,70 (11):237-242.
[5]Badea J, Goldberg J, Mao B, et al. calcium imaging of epileptiformevents with single-cell resolution[J].NeuroBiol,2001,48 (3) 215-227.
[6]梁军潮,徐波涛,王伟民,等.低剂量伽玛刀照射对致痫大鼠皮层及海马神经元c-fos和nNOS表达的影响[J].中国微侵袭神经外科杂志,2008,13(1)：22-24.
[7]Beck EJ, Covar rubias M. Kv4 channels exhibit modulation of closed-state inactivation in inside2out patches [J]. Biophys J,2001,81 (2):867-883.
[8]Moil Y, Kondziolka D, Balzer J, et al.Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy [Jj.Neurosurgery,2000,46(1):157-168.
[9]伍犹梁,梁军潮,詹纯列,等.锂-匹罗卡品颞叶癫痫模型的建立及苔藓纤维出芽的动态变化[J].中国医学比较杂志,2009,19(6)：43-46.
[10]Malis LI, Rose JE, Kruger L, et al. Production of laminar lesions in the cerebral codex by deuteron irradiation. In:Haley Xj Snider Rs (eds)Response of the nervous systemto ionizing radiation[M]. New York:Academic Press,1962,359-368.
[11]Regis J, Bartolomei F,Rey M,et al. Gamma knife surgery for mesial temporal lobe epilepsy[J].Epilepsia.1999,40(11):1551-1556.
[12]刘智良.谭启富,李龄,吴承远.癫痫外科学[M].第二版.北京：人民卫生出版社.2006：138-246.
[13]Chapman AG.Glutamate and epilepsy [J]. Nutr,2004,130 (4S Suppl):1043S.
[14]Rowley HL.Decreased GABA release epilepsy[J]. Neuroscience,2001,68(2):415.
[15]Coulter DA.Epilepsy-associated plasticity in gamma-aminobutyci acid receptor expression, function, and inhibitory synaptic properties[J].Int Rev Neurobiol,2001, 45:237.
[16]Kondziolka D, Lunsford LD, Classen D. Radiobiology of radiosurgery: Part I. The normal rat brain model[J]. Neurosur ery.1992,3,1(21):271-279.
[17]Regis J, Peragui JC, Rey M, et. First selective amygdalohip pocampal radiosurgery for mesial temporal lobe epilepsy[J]. Stereotact Funct Neurosurg,1995, 64 suppl 1:193-201.
[18]刘阿力,张建国,王忠诚,等.伽玛刀照射培养的海马神经元形态结构的变化[J].中华医学杂志,1998,8,78,(8)：(624-626)
[2]Morimoto K, FahnestockM, Racine RJ. Kindling and status epilepticus models of epilepsy:rewiring the brain[J]. ProgNeurobiol,2004,73 (1):1260-1269.
[3]伍犹梁,梁军潮,詹纯列,等.锂-匹罗卡品颞叶癫痫模型的建立及苔藓纤维出芽的动态变化[J].中国医学比较杂志,2009,19(6)：43-46.
[4]Racine RJ. Modification of seizure activity by electrical stimulation Ⅱ Motor seizure [J]. Electroencephalogr Clin Neurophysiol,1972,32(3):281-294.
[5]Glien M, Brandt C, Potschka H, et al. Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy[J]. Epilepsia, 2002,43 (4):350-357.
[6]Blanco MM, DosSantos Jr JG, Perez-Mendes P, Kohek SR, Cavarsan CF, Htlmmel M, Albuquerque C, Mello LE. Assessment of seizure susceptibility in pilocarpine epileptic and nonepileptic Wistar rats and of seizure reinduction with Pentylenetetrazole and electroshock models. EPilePsia.2008 Nov 19.[Epub ahead of print]
[7]Cavalheiro EA. The pilocarpine model of epilepsy[J].Ital J Neuro Sci,1995,16(12):33-38.
[8]Voutsinos-Porche B, Koning E, Kaplan H, et al.Temporal patterns of the cerebral inflammatory response in the rat lithium2pilocarpine model of temporal lobe epilepsy[J]. Neurobiol Dis,2004,17 (3):385-402.
[9]梁益,孙宏斌.氯化锂-匹罗卡品癫痫模型研究[J].实用医院临床杂志,2008,5(3)：112-115.
[10]中华人民共和国卫生部药典委员会编.临床用药须知.中华人民共和国药典.二部.北京：化学工业出版社,1996.38-42.
[1]Romanelli P, Anschel DJ. Radiosurgery for epilepsy[J]. LancetNeurol,2006,5 (7):613-620.
[2]Eder HG, Feichting M, Pieper T, et al. Gamma knife radiosurgery for callosotomy in children with drug-resistant epilepsy [J]. Childs Nerv Syst, 2006,22(8):1012-1017.
[3]梁军潮,徐波涛,杨红军,等.低剂量伽玛刀对致痫大鼠皮层及海马神经元Fos表达的影响[J].立体定向和功能性神经外科杂志,2006,19(1)：28-31.
[4]梁军潮,徐波涛,杨红军,等.小剂量伽玛刀对致痫大鼠脑神经元nNOS表达的影响[J].中国微侵袭神经外科杂志,2006,11(1)：24-26.
[5]Dillon WP, Barbaro N. Noninvasive surgery for epilepsy:the era of image guidanee[J]. AJNR Am J Neuroradiol,1999,20(2):185.
[6]Regis J, Peragui JC, Rey M, et al. First seleetive amygdalohippoeampal radiosurgery for'mesial temporal lobe epilepsy'[J]. Stereotaet Funct Neurosurg,1995,64(suppl 1):193-201.
[7]Regis J, Bartolomei F, Rey M, et al. Gamma knife surgery for mesial temporal lobe epilepsy[J]. Epilepsia,1999,40(1):1551-1556.
[8]Regis J, Rey M, Bartolomei F, et al. Gamma knife surgery in mesial temporal lobe epilepsy:a prospeetive multieenter study[J]. Epilepsia, 2004,45(5):504-515.
[9]Kawai K, Suzukil, Kurita H, et al. Failure of low-dose radiosurgery to control temporal lobe epilepsy[J]. J Neurosurg,2001,95(5):883 887.
[10]Sun B, DeSalles AA, Medin PM, et al. Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery [J]. Exp Neurol.1998 Dec;154(2):691-695.
[11]梁军潮,徐如祥,王伟民,等.低剂量伽玛刀照射癫痫大鼠脑神经元的超微结构研究[J].中国微侵袭神经外科杂志,2005；10(2)：83-85.
[12]Liscak R, Vladyka V, Novotny J Jr, et al.Leksell gamma knife lesioning of the rat hippocampus:the relationship between radiation dose and functional and structural damage[J].J Neurosurg.2002 Dec;97(5 Suppl):666-673.
[13]Regis J, Kerkerian-Legoff L, Rey M, et al. First biochemical evidence of differential functional effects following Gamma knife surgery[J]. Stereotact and functional neurosurgery 1996,66(suppl 1):29-38.
[14]Gerszten PC. Adelson PD, Kondziolka D, et al. Seizure out come in children. Treated for arteriovenous Malformations using Gamma knife radiosurgery[J]. Pediatr Neurosurg 1996,24(3):139-147.
[15]李学忠,包仕荛.谷氨酸和脑缺血[J].中国临床康复,2002,6(1)：137-138.
[4]柏干苹,方勇飞,李廷谦.谷氨酸在低氧性脑损伤中的作用[J].中国临床康复,2002,6(22)：3345-3346.
[16]Meldrum BS.Excitotoxicity and selective neuronal loss in epilepsy[J]. Brain Pathol 1993,3:405-412.
[17]Mattew J. D., Dennis DS. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain[J]. Lancet 1993,341:1607-1611.
[18]Sherwin. AL. Neuroactive amino acids in focally epileptic human brain:a review[J]. Neurochem-Res.1999,24:1387-1393.
[19]Moira KB, Whyte SJ, Hardwick LC, et al. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neurophils in vitro[J].J Clin Invest,1993,92:446-448.
[20]Sattler R, Tymianski M. Molecular mechanisms of glutamate receptor-mediated excitoxic neuronal cell death[J].Mol Neurobiol,2001,24(1-3):107-129.
[21]Joanna P, Zhenlin G, Xun W, et al. Group Ⅱ metabotropic glutamate receptors enhance NMDA receptor currents via a prote in kinase C-dependent mechanism in pyramidal neurons of rat prefrontal cortex [J]. J Phyisol,2004,554:765-777.
[22]Mohandas S, Mani J, Borgohain R, et al.Neuroprotection for acute ischemic stroke:An Overview[J]. Neurol India,2002,50(sl):s57-s63.
[23]Meguro R, LuJ, GavriloviciC, poulterMO. Static, transient and permanent organization of GABA receptor expression in calbindin-positive interneurons in response to amygdala kindle dseizures.Neurochemistry.2004,91(1)144-154.
[24]Simister RJ, McLean MA, Barker GJ, Duncan JS. Proton MR spectroscopy of metabolite concentrations intemporal lobe epilepsy and effect of temporal lobe resection.Epilepsy Re.2009,83(2-3):168-176.
[25]Bernard C, Cossart R, Hirsch JC, Esclapez M, Ben-Ari Y. What is GABAergic inhibition?How is it modified in epilepsy? Epilepsia.2000, 41 (suppl 6):890-595.
[1]Romanelli P, Anschel DJ. Radiosurgery for ep ilep sy[J]. LancetNeurol,2006,5 (7):613-620.
[2]Avanzini G, Franceschetti S. Cellular bi ol ogy of ep ilep t ogenesis[J]. Lancet Neurology,2003,2 (1):33-42.
[3]梁传栋,赵文清,李文玲,等.伽玛刀对大鼠皮层神经元钠电流的影响[J]. 中国神经精神疾病杂志,2008,34(4)：212-215.
[4]Bartol omei F, MassacrierA, ReyM, et al. Effect of gamma kniferadiosurgery on rat brain s odium channel subunit mRNA exp res-sion[J]. Stereotact Funct Neur osurg,1998,70 (11):237-242.
[5]Badea J, Goldberg J, Mao B, et al. calcium imaging of epileptiformevents with single-cell resolution[J].NeuroBiol,2001,48 (3) 215-227.
[6]梁军潮,徐波涛,王伟民,等.低剂量伽玛刀照射对致痫大鼠皮层及海马神经元c-fos和nNOS表达的影响[J].中国微侵袭神经外科杂志,2008,13(1)：22-24.
[7]Beck EJ, Covar rubias M. Kv4 channels exhibit modulation of closed-state inactivation in inside2out patches [J]. Biophys J,2001,81 (2):867-883.
[8]Moil Y, Kondziolka D, Balzer J, et al.Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy [Jj.Neurosurgery,2000,46(1):157-168.
[9]伍犹梁,梁军潮,詹纯列,等.锂-匹罗卡品颞叶癫痫模型的建立及苔藓纤维出芽的动态变化[J].中国医学比较杂志,2009,19(6)：43-46.
[10]Malis LI, Rose JE, Kruger L, et al. Production of laminar lesions in the cerebral codex by deuteron irradiation. In:Haley Xj Snider Rs (eds)Response of the nervous systemto ionizing radiation[M]. New York:Academic Press,1962,359-368.
[11]Regis J, Bartolomei F,Rey M,et al. Gamma knife surgery for mesial temporal lobe epilepsy[J].Epilepsia.1999,40(11):1551-1556.
[12]刘智良.谭启富,李龄,吴承远.癫痫外科学[M].第二版.北京：人民卫生出版社.2006：138-246.
[13]Chapman AG.Glutamate and epilepsy [J]. Nutr,2004,130 (4S Suppl):1043S.
[14]Rowley HL.Decreased GABA release epilepsy[J]. Neuroscience,2001,68(2):415.
[15]Coulter DA.Epilepsy-associated plasticity in gamma-aminobutyci acid receptor expression, function, and inhibitory synaptic properties[J].Int Rev Neurobiol,2001, 45:237.
[16]Kondziolka D, Lunsford LD, Classen D. Radiobiology of radiosurgery: Part I. The normal rat brain model[J]. Neurosur ery.1992,3,1(21):271-279.
[17]Regis J, Peragui JC, Rey M, et. First selective amygdalohip pocampal radiosurgery for mesial temporal lobe epilepsy[J]. Stereotact Funct Neurosurg,1995, 64 suppl 1:193-201.
[18]刘阿力,张建国,王忠诚,等.伽玛刀照射培养的海马神经元形态结构的变化[J].中华医学杂志,1998,8,78,(8)：(624-626)