梭曼和毒扁豆碱引起大鼠脑电癫痫波的M和N胆碱能成分

在加拉碘铵麻痹, 人工呼吸维持和甲基阿托品预防的大鼠上, 梭曼0.1 mg·kg^-1 im (n=24)或毒扁豆碱30.0 mg·kg^-1 iv (n=18)使全部大鼠脑电图(EEG)上出现早期持续很短的紧张性癫痫波和随后持续很长的阵挛性癫痫波. 中枢N受体激动剂烟碱1.0 mg·kg^-1 iv (n=38)和中枢M受体激动剂槟榔碱150 mg·kg^-1 iv (n=46)或匹鲁卡品380 mg·kg^-1 iv (n=24)能分别在EEG癫痫波的特征, 出现时间和持续时间上模拟出上述早期紧张性癫痫波和随后的阵挛性癫痫波. 预先小剂量iv烟碱使中枢N受体脱敏或给小剂量N受体拮抗剂美加明保护中枢N受体后, 梭曼只能引起潜伏 期较长且持续很久的阵挛性癫痫波. 胆碱酯酶抑制剂梭曼和毒扁豆碱较大剂量引起大鼠EEG癫痫波可能的机理是过量的乙酰胆碱作用于潜伏期短, 容易脱敏的N受体出现早期持续很短的EEG紧张性癫痫波, 又作用于潜伏期较长, 不容易脱敏的M受体, 出现稍后的EEG阵挛性癫痫波.     

诺氟沙星侧脑室点燃大鼠癫痫及脑超微结构变化

目的：观察诺氟沙星对ＥＥＧ的影响和对脑组织超微结构的毒性作用，方法：大鼠右侧脑室注射诺氟沙星１５０和３００μｇ．ｋｇ＾－１，于皮层感觉运动区记录ＥＥＧ并观察脑组织超微结构的变化。结果：大鼠ＥＥＧ均出现痫样放电，两组大鼠右侧和左侧棘波发生时间为１６８±１２９，５１±３５ｓ和２７６±１３８，１１８±６５ｓ，以注射侧较早发生，波形多变，幅度和频率逐步增大，并伴肢体抽搐的行为改变，电镜下３００μｇ．ｋｇ＾     

诺氟沙星侧脑室点燃大鼠癫痫及脑超微结构变化

目的:观察诺氟沙星对EEG的影响和对脑组织超微结构的毒性作用。方法:大鼠右侧脑室注射诺氟沙星150和300μg·kg~(-1)后,于皮层感觉运动区记录EEG并观察脑组织超微结构的变化。结果:大鼠EEG均出现痫样放电,两组大鼠右侧和左侧棘波发生时间为168±129,51±35s和276±138,118±65s。以注射侧较早发生,波形多变,幅度和频率逐渐增大,并伴肢体抽搐的行为学改变。电镜下,300μg·kg~(-1)组大鼠双侧大脑皮层、海马及小脑均有明显的神经元变性,包括高尔基复合体、粗面内质网及神经毡的髓样变性、细胞质肿胀、细胞核及染色质溶解、胶质细胞坏死等,并出现亮神经元和暗神经元改变,以暗神经元为著。结论:诺氟沙星点燃癫痫后,大鼠脑组织超微结构受到广泛损伤。     

匹鲁卡品癫痫模型慢性期大鼠海马苔藓纤维出芽的观察

目的观察腹腔注射匹鲁卡品后大鼠痫性发作及海马苔藓出芽。方法 Wistra大鼠60只随机分为模型组和对照组,每组30只,均进行Nissl染色及Timm银染。并于实验当天行脑电图检查。结果腹腔注射匹鲁卡品后大鼠可见急性癫痫发作,观察慢性期自发性发作。Nissl染色示模型组各区评分两两比较,结果示CA3、门区与CA1区神经元缺失差异有统计学意义（P〈0.05）。Timm银染示2组苔藓纤维出芽Timm银染颗粒评分比较,差异有统计学意义（P〈0.05）。结论 腹腔注射匹鲁卡品简单复制了人类癫痫的基本病理特征,是研究癫痫的一种简便方法。     

匹鲁卡品致痫大鼠皮质和海马C-fos的表达变化

目的:观察匹鲁卡品致痫动物模型中C-fos蛋白在癫痫发作不同阶段的表达变化。方法:采用匹鲁卡品诱发癫痫状态模型,观察大鼠的行为学改变,用免疫组织化学法标记显示在癫痫发作不同阶段脑内C-fos的表达变化。结果:在海马CA1区、CA3区、海马齿状回、大脑皮层中C-fos阳性细胞数表达在癫痫发作的不同阶段有明显不同(P<0.05)。在癫痫的早期阶段(第Ⅰ和Ⅱ阶段),C-fos表达主要分布在皮层区,随着痉挛程度的增加,C-fos表达完全扩大的区域有海马齿状回、CA1、CA3区和皮层区,表现在第Ⅳ和第Ⅴ阶段。结论:在癫痫发作的早期阶段C-fos有较好的表达,早期进行监测及干预,以减少脑内神经元的损伤。     

癫痫患儿脑电图与心电图改变的临床分析(附104例报告)

目的 探讨癫痫患儿癫痫发作与发作间期动态脑电图和心电图的变化特点. 方法 回顾性分析我院104例行24 h动态脑电图与心电图同步监测癫痫患儿的临床资料. 结果 本组动态心电图出现异常34例,占32.7%;出现以颞部为主的异常脑电波64例,动态心电图异常率为37.5%,心电图异常表现方式最多,室性早搏、心律不齐、传导阻滞...     

奥卡西平和卡马西平对成人部分性癫痫认知功能及脑电图的影响

目的比较奥卡西平和卡马西平对成人部分性癫痫患者认知功能及脑电图的影响。方法符合诊断标准的成人部分性癫痫患者,随机分为卡马西平治疗组(n=64)和奥卡西平组(n=92),进行单药治疗。分别于治疗前及治疗后6个月行认知功能测评及长程视频脑电图(VEEG)检查。分析2组治疗前后认知功能及脑电图的变化。结果部分性癫痫患者经奥卡西平或卡马西平单药治疗6个月后,韦氏成人智力量测评提示奥卡西平组认知功能较治疗前有所改善,卡马西平组治疗前后变化不明显;脑电图检查示治疗6个月后,奥卡西平组有73.9%的患者癫痫样放电减少超过50%,卡马西平组只占53.1%,2组差异有统计学意义(P<0.05);卡马西平组治疗后α功率值较治疗前显著降低(P<0.05),θ功率值显著增加(P<0.05),奥卡西平组治疗前后α功率值无明显改变(P>0.05),θ功率值明显增加(P<0.05)。结论奥卡西平与卡马西平相比,对成人部分性癫痫患者认知功能改善更明显,对痫样放电的抑制作用较强,且对脑电背景活动影响较小     

癫痫患儿脑电图与心电图改变的临床分析(附104例报告)

目的 探讨癫痫患儿癫痫发作与发作间期动态脑电图和心电图的变化特点. 方法 回顾性分析我院104例行24 h动态脑电图与心电图同步监测癫痫患儿的临床资料. 结果 本组动态心电图出现异常34例,占32.7%;出现以颞部为主的异常脑电波64例,动态心电图异常率为37.5%,心电图异常表现方式最多,室性早搏、心律不齐、传导阻滞、室上性心动过速均可在同一患儿动态心电图中见到占79.2%;出现以额叶为主的异常脑电波22例,动态心电图异常率为22.7%,多表现为窦性心动过速;出现以顶、枕叶为主的异常脑电波10例,动态心电图异常率为20.0%,出现心律不齐1例;多灶性或广泛性放电8例,动态心电图异常率为37.5%,心律不齐2例.动态心电图出现异常的34例中,动态脑电图主要表现为慢波增多,或双侧颞区、额区、中央区和顶区出现大量中高电位局灶性棘(或尖)波、(多)棘(或尖)慢复合波,或双侧颞部局限性(或节律性)中高波幅的慢波θ或δ波.监测期间动态心电图异常的34例癫痫患儿,发作与发作间期的动态心电图无明显改变者占38.2%,发作前后伴窦性心动过速或心律失常占61.8%. 结论 癫痫患儿癫痫发作期动态心电图发生异常的概率较发作间期高,与癫痫发作部位及动态脑电图波形异常存在一定联系.     

连续脑电监测对进展性脑梗死的预测价值

进展性脑梗死（progressive cerebral infarction，PCI）是指缺血性卒中后神经功能缺失症状较轻微，但呈渐进性加重，在48h内仍不断进展，直至出现较严重的神经功能缺损，严重影响患者预后,早期发现并进行干预至关重要。本研究探讨我科2004年4月-2005年7月应用长程脑电监测的120例脑梗死患者脑电图（EEG）变化与临床表现的关系，了解连续脑电监，测（continuous　electroencephalogram　monitoring，CEEG）对梗死进展的预测价值及对预后的评估作用。     

Subchronic physostigmine pretreatment in marmosets: absence of side effects and effectiveness against soman poisoning with negligible postintoxication incapacitation.

Subchronic pretreatment with physostigmine (PHY) (0.0125 mg/kg/h) leading to a blood acetylcholinesterase inhibition of about 30% caused no side effects when applied to marmoset monkeys. This was evident on behavioral parameters and on EEG and cortical visual evoked response. Furthermore, this treatment regime, followed by atropine as postintoxication therapy, protected the marmosets against lethality after a 2 x LD50 dose of soman with negligible postintoxication incapacitation. These findings suggest that a symptom-free pretreatment with subchronic PHY could protect man sufficiently against severe soman intoxication.     

Muscarinic receptor dysfunction induced by exposure to low levels of soman vapor.

In the eye, it has been previously reported that exposure to a cholinesterase inhibitor results in a reduced miotic response following prolonged exposure and a decreased miotic response to the cholinergic agonists. However, no studies exist that characterize the effect of a single low-level vapor exposure to a nerve agent on parasympathetic function in the eye or determine the threshold dose for such an effect. The present study investigated the hypotheses that a single low-level exposure to soman vapor would result in dysfunction of the parasympathetic pathway mediating the pupillary light reflex resulting from a loss of muscarinic receptor function on the pupillary sphincter muscle. Adult male rats were exposed to soman vapor in a whole-body dynamic airflow exposure chamber. Rats exposed to low levels of soman vapor dose-dependently developed miosis (threshold dose between 4.1 and 6.1 mg-min/m3). Pupil size returned to preexposure levels within 48 h due to desensitization of pupillary muscarinic receptors, as assessed by the pupillary response to the muscarinic agonist oxotremorine. An attenuated pupillary light reflex was also present in miotic animals (threshold dose near 6.1 mg-min/m3). While pupil size recovers within 48 h, other measures of pupillary function, including the light reflex, acetylcholinesterase activity, and muscarinic receptor responsiveness, did not return to normal for up to 10 days postexposure. Recovery of the light reflex coincided with the recovery of pupillary muscarinic receptor function, suggesting that the attenuation of the light reflex was due to receptor desensitization.     

Effects of nicotinic agonists and antagonists on spatial working memory in normal adult and aged rats

The present study had two goals (1) to examine the effects of treatments with nicotinic agonist (nicotine) and antagonist (mecamylamine) on working memory in normal adult rats (14 months of age), and (2) to determine if treating aged (36 to 42 months of age), memory-impaired rats with nicotine could improve their memory function. Memory testing was carried out using a delayed non-matching to position paradigm in a T-maze. Rats were trained to run down one arm of the maze (e.g., right) on an information run and then, after a variable memory delay period of 10, 90, or 180 sec, run down the other arm (e.g., left). In normal adult rats after water injection, memory accuracy was inversely related to memory delay (> 90, 75, and 67% accuracy at the 10, 90, and 180 sec delays, respectively). Administration of nicotine (0.1 or 0.4 mg/kg), or mecamylamine (2.5 or 5 mg/kg), or combinations of these drugs had no significant effects on memory in these rats. However, mecamylamine alone or in combination with nicotine reduced running speed in the T-maze in normal adults, indicating that the drugs did produce some behavioral effects. In aged rats, memory accuracy after water injection was much lower than that of younger adults, averaging 64, 57, and 50% at 10, 90, and 180 sec delays. Interestingly, nicotine injections of 0.1 or 0.4 mg/kg resulted in highly significantly improved accuracy in the memory task. The deficit in memory accuracy in aged rats, evident even at the shortest delay period (10 sec), suggests that the rats may have had impairments in attention or visual discriminatory ability. If this is so, then the beneficial effects of nicotine observed in this study may be more related to its effects on attention rather than memory directly. © 1994 Wiley-Liss, Inc.     

Comparison of the ability of direct- and indirect-acting nicotinic agonists to induce nicotinic receptor up-regulation in rat cerebral cortex

Chronic twice daily systemic administration of nicotine (1 mg [2 μmol]/kg, sc) over 10 days to rats produced a significant increase in the apparent B_max for cortical nicotinic receptors. Similar results were obtained whether the labeled ligand employed was [³H]methylcarbamylcholine ([³H]MCC) or [³H]cytisine: Rats were treated twice daily for 10 days with the cholinesterase inhibitor physostigmine (25 μg [64 nmol]/kg, sc) to indirectly activate nicotinic receptors. This regimen inhibited cortical cholinesterase activity by about 51%. Binding analysis of physostigmine-treated rat cortical tissue indicated that while the B_max for muscarinic receptors was significantly reduced, there was no change in the binding parameters for neuronal nicotinic receptors. In the next series of experiments, chronic twice daily intracerebroventricular (icv) injection of 30 μg [108 nmol] of MCC, like nicotine, also produced a significant increase in the B_max for cortical nicotinic receptors. MCC treatment also produced a small but significant increase in the apparent K_d. Twice daily icv injection of 6 μg [23 nmol] of the competitive nicotinic antagonist dihydro-β-erythroidine hydrobromide (DHBE) for 10 days did not itself alter the apparent B_max for cortical nicotinic receptors. In a separate group of rats 6 μg [23 nmol] icv of DHBE preceded by 15 min the icv injection of 30 μg [108 nmol] of MCC. This regimen was administered twice daily for 10 days. Under these conditions the DHBE produced a significant 44% inhibition of the MCC-induced increase in B_max. Antagonist pretreatment also blocked the small MCC-induced increase in K_d. Thus, direct activation of the agonist binding site of the neuronal nicotinic receptor following chronic administration of nicotine or the acetycholine-like MCC leads to receptor up-regulation. Indirect activation through cholinesterase inhibition was not effective in this regard. © 1994 Wiley-Liss, Inc.     

Determination of anti‐convulsant and life‐preserving capacities of three types of auto‐injector therapies against soman intoxication in rats

More effective countermeasures against nerve‐agent poisoning are needed, because current ones do not protect sufficiently, particularly the central nervous system (CNS). The purpose of the present study was to make a comparison of the antidotal capabilities of atropine/obidoxime/diazepam (termed the obidoxime regimen), atropine/HI‐6 (1‐[([4‐(aminocarbonyl)pyridinio]methoxy)methyl]‐2‐[(hydroxyimino)methyl]pyridinium)/avizafone (termed the HI‐6 regimen), and scopolamine/HI‐6/physostigmine (termed the physostigmine regimen) against various doses of soman (2, 3, 4 x LD₅₀). The results showed that each regimen administered twice (1 min and 5 min after exposure) effectively prevented or terminated epileptiform activity within 10 min. However, the regimens differed markedly in life‐saving properties with the physostigmine regimen ranking highest followed in descending order by the HI‐6 and obidoxime regimens. Pretreatment with pyridostigmine increased the potency of the HI‐6 regimen, but not the obidoxime regimen. The latter regimen administered thrice (1 min, 5 min, and 9 min after exposure) did not compensate for the insufficiency. In half of the rats that lived for 7 days, neuropathology was unexpectedly observed predominantly in the left hemisphere unrelated to whether they seized or not. Local glutamatergic excitotoxic activity may occur even if manifest toxic signs are absent. The physostigmine regimen has excellent antidotal capacity, but the very narrow therapeutic window (< 10 min) makes it unsuitable for use in the field. The HI‐6 regimen appears to constitute an efficacious therapy against lower doses of soman (2 and 3 x LD₅₀). Copyright © 2012 John Wiley & Sons, Ltd.     

Correlation between signs of toxicity and some biochemical changes in rats poisoned by soman

Inhibition and regeneration rate of brain, blood and diaphragm cholinesterase were studied after a sublethal or also a lethal dose of soman in rats; plasma glucose concentration, spontaneous motor activity and the toxic symptomes observed during the acute phase of poisoning and during the recovery period were also studied.After a single injection of soman, a close relationship existed between the severity of the symptoms of poisoning and the level of cholinesterase inhibition during the first 30–120 min in the acute phase. 2–48 hr after the injection the toxic symptoms, hyperglycemia and depression of spontaneous motor activity had disappeared, whereas cholinesterase activity in blood, brain and diaphragm remained unchanged.Thus the relatively rapid spontaneous recovery of animals from the toxic effects of soman is not caused by enzyme regeneration. Some adaptation may occur at synapses under these abnormal situations, which is responsible for the rapid spontaneous recovery of animals poisoned by soman.     

毒扁豆碱对大鼠的镇痛效应及静脉注射毒扁豆碱与蛛网膜下腔注射吗啡的相互作用(英文)

目的 :观察在术后不同阶段静脉注射胆碱酯酶抑制剂毒扁豆碱对鼠痛阈的影响 ,以及静注毒扁豆碱和蛛网膜下腔注射吗啡的药物相互作用。方法 :6组SD大鼠 ,置入蛛网膜下腔和股静脉导管。采用辐射热刺激诱发的鼠腿撤退试验测痛阈 ,测试分别于术后 1～ 3h和术后 3d进行。动物分别接受静注毒扁豆碱、蛛网膜下腔注射吗啡及两者联合给药。比较术后 1～ 3h和 3d各种药物对痛阈的影响、联合给药与单独给药对痛阈的影响。药物的镇痛效应以最大可能效应的百分比 ( %MPE)表示。结果 :毒扁豆碱术后 1～ 3h静注导致 %MPE明显提高 ;毒扁豆碱与吗啡的联合给药效应在术后早期更明显 ;小剂量联合给药的镇痛作用明显大于双倍剂量单独给药的镇痛作用 ;联合给药的测得效应值明显大于估计叠加效应值。结论 :胆碱酯酶抑制剂毒扁豆碱在术后早期产生镇痛作用 ;静注毒扁豆碱与蛛网膜下腔注射吗啡的联合给药呈协同效应。     

神经性毒剂梭曼中毒致犬心电图的变化及宾赛克嗪的救治作用

目的：观察神经性毒剂梭曼中毒导致犬心电图和心肌酶的变化及新型抗毒剂宾赛克嗪（benthiactzine）的解救作用。方法：健康成年雄性杂种犬7只,体重12-15kg。在麻醉状态下,每次肌肉注射1/3LD梭曼（1LD=10μg/kg）,每10min追加1次的累积染毒;以平均动脉压降至40-45mmHg（1mmHg=0.133kPa）为循环衰竭标准。观察在梭曼染毒前后及宾赛克嗪救治后犬的血压、心率、心电图和心肌酶的变化。结果：染毒后诱发犬进行性循环衰竭,心率减慢,房室传导阻滞,部分P波消失,出现室性逸搏,结性心律;T波高耸,波峰尖锐。血液中肌酸磷酸激酸同工酶（CK-MB）和乳酸脱氢酶（LDH）水平显著增加（P〈0.05）,表明梭曼染毒导致犬循环衰竭发生心脏受损明显。宾赛克嗪0.1mg/kg静脉注射,57.1%的犬在3-5min恢复窦性心律,心率增加,房室传导阻滞消失,心电图T波可基本恢复,但血液中CK-MB和LDH在救治后无显著恢复。结论：胆碱酯酶抑制剂类毒物梭曼中毒可引起严重心律失常,宾赛克嗪可给予有效的救治。