Amygdala kindling in the WAG/Rij rat model of absence epilepsy

PURPOSE: The kindling model in rats with genetic absence epilepsy is suitable for studying mechanisms involved in the propagation and generalization of seizure activity in the convulsive and nonconvulsive components of epilepsy. In the present study, we compared the amygdala kindling rate and afterdischarge characteristics of the nonepileptic Wistar control rat with a well-validated model of absence epilepsy, the WAG/Rij rat, and demonstrated the effect of amygdala kindling on spike-and-wave discharges (SWDs) in the WAG/Rij group. METHODS: Electrodes were stereotaxically implanted into the basolateral amygdala of rats for stimulation and recording and into the cortex for recording. After a recovery period, the animals were stimulated at their afterdischarge thresholds. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated by using Racine's 5-stage scale. RESULTS: All nonepileptic control and four of seven WAG/Rij animals reached a stage 5 seizure state, whereas three animals failed to reach stage 3, 4, or 5 and stayed at stage 2 after application of 30 stimulations. Interestingly, WAG/Rij rats, resistant to kindling, demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation than did the kindled WAG/Rij animals. Additionally, the cumulative total duration and the number of SWDs after the kindling stimulation were statistically increased compared with SWDs before kindling stimulation. CONCLUSIONS: The results of our study demonstrate that the progress of amygdala kindling is changed in rats with genetic absence epilepsy, perhaps as a consequence of the hundreds of daily SWDs.     

Effect of L-arginine on synaptosomal mitochondrial function

Objective: Specific aim of this study is to elucidate the direct effects of l-arginine on the synaptosomal neurotransmission related to the mitochondrial respiratory function. Methods: Using isolated endbrains from wild-type mice (ICR), crude synaptosome was analyzed for their concentration of γ-aminobutyric acid (GABA) and glutamate (Glu) with/without addition of l-arginine. We analyzed the contents of releasing amino acids evoked by high potassium condition and uptake of them in three separated fractions (cytosol, vesicles, and intact mitochondria). The oxygen consumption was also measured by oxygen electrode. Results: The entire uptakes of GABA and Glu were inhibited by rotenone (about 30 nmol/mg protein) with dose-dependent manner and showed a plateau at about 70% of total uptake. l-arginine inhibited the uptake of Glu logarithmically, however it showed no change in uptake of GABA. The contents of GABA and Glu in synaptosome were decreased in the presence of l-arginine. l-arginine enhanced the respiration of state II by succinate on synaptosomal respiration, although the respiration of synaptosomal mitochondrial fraction and the respiratory chains enzyme activities were almost unaffected by l-arginine. In the presence of rotenone, l-arginine decreased the uptake of Glu without changing the uptake of GABA, increased the releasing of GABA, and may modulate the excitability of neuronal state on the cytosol, cytomembrane, and/or organelles except for mitochondria. Conclusions:l-arginine may modulate excitation by neurotransmitters at nerve endings, in relation to potentiated respiratory metabolism of succinate in synaptosomes. Such effects might contribute to alleviation of stroke-like symptoms in MELAS.     

咪达唑仑对利多卡因致惊厥作用的影响

目的从致惊厥的行为学、安全性角度探讨咪达唑仑对利多卡因致惊厥作用的影响。方法皮下注射咪达唑仑20min后,腹腔注射不同剂量利多卡因,观察小鼠惊厥潜伏期、持续时间、未惊厥率及其死亡率;并按序贯法计算咪达唑仑对利多卡因致惊厥半数有效量（EDS0）和半数致死量（LD50）的影响。结果1．0mg／kg咪达唑仑可显著延长利多卡因致小鼠惊厥的潜伏期（P〈0．01）、显著缩短惊厥持续期（P〈0．01）、减少惊厥的发生;且2mg／kg、5mg／kg的咪达唑仑可减小利多卡因的LD50（P〈0．01）。结论1mg／kg咪达唑仑可拮抗利多卡因的致惊厥作用,结果对临床联合用药有一定的参考意义。     

c-FOS and n-NOS reactive neurons in response to circulating Phoneutria nigriventer spider venom

Drugs and neurotoxins activate specific neural circuits by increasing or decreasing the formation and release of neurotransmitters, such as nitric oxide (NO), and by inducing immediate early genes, such as FOS. We have previously shown that Phoneutria nigriventer spider venom (PNV) impairs the microtubule-dependent transcellular barrier of the blood-brain interface and causes structural alterations in perivascular astrocytic end-feet without producing morphological changes in central neuronal cells. In the present study, we used FOS and neuronal nitric oxide synthase (n-NOS) immunolabeling to investigate the ability of PNV to activate the central nervous system. Three groups of rats were used: the first group received a sublethal dose of PNV (850 microg/kg, via a tail vein), the second received an equal volume of 0.9% saline (sham group) and the third group received no injection. Envenomed rats showed salivation, lachrymation, tremors and flaccidity followed by spastic paralysis of the hind limbs and convulsions. Cryosections (30 microm thick) were serially collected at 600 microm intervals for free-floating immunohistochemical analysis. FOS-like positive neurons predominated in motor-related areas such as dorsolateral (dlPAG) and ventral periaqueductal gray matter (vPAG), frontal (FCM) and parietal motor cortex (PCM), and periventricular thalamic nucleus (PTN) and in acute stress-related areas (rhinal cortex and lateral septal nuclei). The greatest relative increases in FOS-like positive neurons occurred in the vPAG, PCM and PTN motor-related areas. n-NOS-positive neurons predominated in the periventricular thalamic nuclei, followed by the dorsolateral periaqueductal gray matter and parietal cortex motor area. The marked activation of motor areas and, to a lesser extent, of acute stress-related areas suggested the involvement of neuronal pathways in these regions in the response to envenoming by PNV. In addition, the occurrence of n-NOS immunolabeling in some anatomical regions with FOS-like positive neurons suggests that NO may modulate the response to PNV in these regions.     

Ovariectomy aggravates convulsions and hippocampal γ-aminobutyric acid inhibition induced by cyclosporin A in rats

The possible cyclosporin A application for rheumatoid arthritis that develops preferentially in middle-aged women raises concerns about adverse effects of cyclosporin A, including neurotoxicity in patients with climacterium. The present study was aimed at elucidating the effect of cyclosporin A on the convulsive activity and γ-aminobutyric acid (GABA) neural activity of the hippocampus in ovariectomized rats, as a menopause/climacterium model. Ovariectomy markedly aggravated the effect of repeated administration of cyclosporin A (40 mg/kg, once a day for 5 or 6 days), convulsions and reduction of the basal GABA levels and aminooxyacetic acid-evoked GABA accumulation. These aggravations were blocked by estradiol replacement. The present findings demonstrated that ovariectomy increased the susceptibility to cyclosporin A-induced convulsions by accelerating an inhibitory action of cyclosporin A on GABA neural activity in the hippocampus, this being blocked by estrogen replacement. Menopause/climacterium is, therefore, included in the risk factors for cyclosporin A-induced neurotoxicity and this risk is lowered by estrogen replacement therapy.     

热性惊厥儿童IMPA2基因多态性分析

目的:分析IMPA2基因多态性与儿童热性惊厥易感性的关系。方法:采用病例-对照研究方法和聚合酶链反应-限制片断长度多态分析技术(PCR-RFLP),检测热性惊厥病例组和健康对照组的IMPA2基因多态性。结果:IMPA2基因单核甘酸多态性位点159T>C病例组与对照组基因型分布无显著差异,而单核甘酸多态性位点558C>T病例组与对照组基因型分布有显著差异(P<0.01)。结论:IMPA2的基因位点558C>T可能是热性惊厥的多基因遗传位点之一。     

Convulsant activity of sitafloxacin and its interactions with anti-inflammatory drugs in mice

We studied the convulsant activity of sitafloxacin, a newly developed quinolone, and its interaction with anti-inflammatory drugs in mice. Intraventricular injections of sitafloxacin and levofloxacin induced convulsions dose-dependently in the mice. The value of the effective dose for producing convulsions in 50% of the mice (ED₅₀) of sitafloxacin was 50.6 nmol/head, whereas that of levofloxacin was 76.7 nmol/head. The convulsant activity of these quinolones was not affected by concurrent administration with anti-inflammatory drugs. From these results obtained in a mouse model, it is suggested that sitafloxacin has weak convulsant activity and that the convulsant activity of sitafloxacin is not enhanced when it is administered with anti-inflammatory drugs.     

安定持续静滴控制中重度新生儿缺氧缺血性脑病惊厥的观察

目的观察持续静滴安定控制中重度新生儿缺氧缺血脑病(HIE)惊厥的疗效。方法选择中重度HIE出现频繁惊厥或惊厥持续状态患儿33例,其中治疗组18例给予安定持续静滴治疗,对照组15例间断给予镇静剂。比较惊厥控制时间。结果治疗组惊厥控制时间(30.39±10.68)min较对照组(60.87±9.49)min明显为短(t=8.65,P<0.01)。在0.05mg/(kg·min)剂量范围内未出现呼吸抑制等明显副作用。结论安定持续静滴控制中重度HIE惊厥发作临床效果良好、安全。     

88例热性惊厥患儿缺铁性贫血相关指标分析

目的了解热性惊厥与缺铁性贫血的关系。方法检测88例热性惊厥患儿的红细胞计数、血红蛋白、红细胞平均容积、红细胞平均血红蛋白、红细胞平均血红蛋白浓度、血清铁、血清铁蛋白,并以同期住院的76例呼吸道、肠道感染而无惊厥患儿为对照组,将两组数据进行统计分析。结果热性惊厥组缺铁性贫血的发生率为61.36%,对照组为43.42%,血红蛋白、血清铁含量与对照组有显著性差异(P<0.05);而且复杂型热性惊厥的缺铁性贫血的发生率占85%,与单纯型比较亦有显著性差异(P<0.05)。结论血清铁与小儿热性惊厥密切相关,缺铁性贫血可能是引起热性惊厥的原因之一。     

控制氯化锂-匹罗卡品诱发惊厥持续状态发作的实验研究

目的:探索有效控制氯化锂-匹罗卡品诱发的大鼠惊厥持续状态(SC)发作,提高实验大鼠存活率的最佳条件。方法:选用成年Wistar鼠25只,经腹腔注射氯化锂和匹罗卡品,诱发大鼠惊厥发作,惊厥发作30min后,分为4个不同止惊剂的处理组和1个对照组。比较不同组间的止惊效果、惊厥持续状况、实验动物死亡率、死亡发生时间,探索有效控制氯化锂鄄匹罗卡品所致惊厥持续状态的最佳止惊措施。结果:(1)使用氯化锂鄄匹罗卡品后诱发惊厥的发生率为100%,不采用止惊治疗惊厥发作将持续17~24h,仅有一只存活,其余4只2~4d死亡。(2)与对照组比较,联合使用地西泮和苯巴比妥能在用药后20min左右控制或减轻惊厥发作,但该组实验动物呼吸道分泌物明显增多,呼吸困难严重,所用动物均死于急性肺水肿。(3)腹腔注射水合氯醛后,5~30min能完全终止惊厥发作,但对改善呼吸困难无明显作用,实验动物于(180.0±34.2)min死亡。(4)注射水合氯醛联合应用阿托品后3~29min内完全控制惊厥发作,同时减少实验动物的呼吸道分泌物,改善呼吸困难,使该组5只动物全部存活。结论:水合氯醛是氯化锂鄄匹罗卡品所致SC模型的有效止惊剂;联用水合氯醛和阿托品才是有效控制该模型急性惊厥发作、提高实验动物生存率的措施。