Effect of oleamide on pentylenetetrazole-induced seizures in rats

Oleamide exhibits antiepileptic activity and significantly decreases the degree of pentylenetetrazole-induced seizures. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 185–187, February, 2008     

The protective effect of dl-tetrahydropalmatine against the development of amygdala kindling seizures in rats

The influence of dl-tetrahydropalmatine (THP), an active component isolated from a Chinese herbal medicine corydalis, was tested on the development of electrically kindled amygdala. The seizure activity was quantified by a ultrasonic system for vertical motion measurements. Intraperitoneal injection of THP (20 or 30 mg kg⁻¹) 30 min before applying the daily kindling stimulus prevented the development of the kindling process. The behavioral seizure score and the motion responses which normally develop during electrical kindling were reduced below their initial values. The results suggest that THP is a very effective antiepileptogenic and anticonvulsant agent when applied to electrically kindled rats.     

Spatiotemporal changes of the N-methyl-D-aspartate receptor subunit levels in rats with pentylenetetrazole-induced seizures

The aim of this study was to examine the expression profiles of N-methyl-D-aspartate (NMDA) receptor subunits in rats during seizure development and kindled process induced by pentylenetetrazole (PTZ). Using quantitative Western blotting, the levels of NR1, NR2A and NR2B subunits were measured in the cortex and hippocampus of rats at different times after PTZ injection. In the early seizure developmental process, both NR1 and NR2A were markedly increased in the cortex, and NR1 was significantly increased in the hippocampus. On the other hand, in the kindled process both NR1 and NR2A decreased in the cortex and hippocampus. However, the NR2B subunit had no appreciable change in both the seizure developmental and kindled process. Therefore, these results showed that expression of NMDA receptors undergoes subunit- and region-related changes in the developmental and kindled seizure of rats induced by PTZ.     

红藻氨酸致(癎)大鼠神经元凋亡的动态研究

目的：探讨红藻氨酸（kainic acid，KA）诱导的癫痫大鼠脑内神经元凋亡在不同部位和致痫后不同时间的变化情况。方法：将50只SD大鼠随机分为对照组和KA组，KA组再按癫痫发作后1天、1周、2周、3周和4周不同时点分为5个亚组。KA注射后，观察大鼠癫痫发作后的行为学变化，采用原位细胞凋亡检测法观察不同部位、不同时点神经元凋亡情况。结果：KA注射后，大鼠出现严重的惊厥，在癫痫发作后1天、1周和4周凋亡细胞明显增多，以齿状回、丘脑和CA3区明显（P〈0．05）。结论：细胞凋亡贯穿KA致痫大鼠癫痫发作后神经元迟发性死亡的全过程。     

青霉素致癎动物模型的电生理研究

目的:探讨青霉素致癫癎大鼠样发作的特点以及可能的电生理机制。方法:在立体定向指导下,将脑电图(EEG)记录电极植入24只Wistar大鼠海马、颞叶和额叶皮质中。手术后1周在大鼠清醒状态下,青霉素300万单位/kg(致组)或等容生理盐水(对照组)腹腔注射后连续描记EEG 120 min,观察大鼠行为表现及海马和大脑皮层EEG变化特点。结果:①青霉素致组大鼠样发作程度均达到Ⅳ-Ⅴ级;②同时在海马和皮层记录到各种形式的癎样放电波,如棘波、棘慢综合波、尖波、尖慢综合波、或阵发性节律等;③大多以同步放电起始,个别以海马或皮层先出现样放电,然后同步化。结论:①青霉素致惊厥大鼠的癎样发作基本上是全面性的,②其EEG主要是大脑皮质、海马同步放电开始。     

多因素所致温病湿热证模型大鼠红细胞免疫功能的变化

目的：探讨高温、高湿环境,同时给予高脂、高糖饲料,并感染不同的病原微生物等因素对大鼠红细胞免疫功能的影响。方法：采用红细胞酵母菌混合花环法测定大鼠红细胞Ｃ３ｂ受体花环数（ＥＣ３ｂＲＲ）和红细胞免疫粘附物（ＥＩＣＲ）花环数。结果：在多因素作用下,模型大鼠外周血中红细胞Ｃ３ｂ受体花环数（ＥＣ３ｂＲＲ）显著降低,而红细胞免疫粘附物（ＥＩＣＲ）升高。除去病原微生物作用,大鼠在高脂高糖、高温高湿环境,ＥＣ３ｂＲＲ显著降低和ＥＩＣＲ水平均显著降低;将动物给予普通饲料,置于高温高湿环境,ＥＣ３ｂＲＲ显著降低,而ＥＩＣＲ水平无显著变化。结论：多因素同时作用所致大鼠温病湿热证模型其红细胞免疫功能发生显著变化     

甜菜碱对戊四氮致痫大鼠海马GFAP、甘氨酸和甘氨酸受体表达的影响

 目的：研究甜菜碱对癫痫大鼠海马胶质细胞原纤维酸性蛋白（GFAP）、甘氨酸(Gly)及甘氨酸受体(GlyR)表达的影响。方法：将健康雄性Wistar大鼠随机分为：正常对照组（腹腔注射生理盐水,1.0 mL生理盐水灌胃);癫痫组（腹腔注射戊四氮,1.0 mL生理盐水灌胃）;甜菜碱高、中、低浓度组（腹腔注射戊四氮,甜菜碱灌胃）;丙戊酸钠组（腹腔注射戊四氮,丙戊酸钠灌胃）。实验结束后大鼠眼眶取血检测血清中同型半胱氨酸的含量;在低温条件下迅速取脑组织,分析Gly含量的变化,免疫荧光检测GFAP的水平,兔疫荧光和Western bloting检测海马区GlyR表达的变化。结果：各组大鼠大发作潜伏期无显著差异(P＞0.05),但是甜菜碱治疗组较癫痫组的首次大发作持续时间显著缩短(P<0.01)。癫痫组同型半胱氨酸的含量与正常组比较显著降低（P<0.01）,甜菜碱高、低浓度组同型半胱氨酸含量与癫痫组比较明显降低（P<0.05）。癫痫组甘氨酸的含量与正常对照组相比显著下降（P<0.01）。甜菜碱高、中、低浓度组甘氨酸的含量与癫痫组比较显著增高（P<0.01）。免疫荧光检测GFAP结果,癫痫组与正常组比较显著增高（P<0.01）,而甜菜碱高中低浓度与癫痫组相比显著降低（P<0.01）。免疫荧光与Western bloting检测GlyR结果,癫痫组GluR的表达与正常对照组相比显著降低（P<0.01）,甜菜碱高、中、浓度组较癫痫组显著升高（P<0.01）。结论：甜菜碱具有较好的抗癫痫作用。     

Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.     

Elevated expression of pleiotrophin in pilocarpine-induced seizures of immature rats and in pentylenetetrazole-induced hippocampal astrocytes in vitro

Pleiotrophin (PTN) is a secreted extracellular matrix (ECM)-associated cytokine that has emerged as an important neuromodulator with multiple neuronal functions. In the present study, we detected and compared the dynamic expression of PTN in the hippocampus and adjacent cortex of immature rats with pilocarpine-induced epilepsy. Moreover, we also confirmed the results by examining PTN expression in hippocampal astrocytes cultured in the presence of pentylenetetrazole (PTZ). Immunohistochemistry showed faint immunostaining of PTN in the control hippocampus and adjacent cortex. Notably, PTN immunoreactivity began to increase in relatively small cells in the hippocampus and adjacent cortex at 2 h and 3 weeks after seizures, and the labeling intensity reached the maximum level in the hippocampus and adjacent cortex at 8 weeks after seizures. Furthermore, we also found that PTZ treatment significantly reduced astrocytic viability in a dose-dependent manner and time-dependently increased expression levels of PTN in hippocampal astrocytes. In conclusion, our data suggest that increased expression of PTN in the brain tissues may be involved in epileptogenesis.     

Wi-Fi decreases melatonin protective effect and increases hippocampal neuronal damage in pentylenetetrazole induced model seizures in rats

AimEpilepsy is a common brain disorder in which the seizures could cause a neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of epilepsy. Some studies indicate that Wi-Fi increases oxidative stress and suppresses antioxidant systems. The aim of this study is to investigate the effect of Wi-Fi on melatonin anticonvulsive effect and oxidative damage in pentylenetetrazole-induced epileptic seizures in rats.MethodsIn our study, we used 30 male Wistar Albino rats, 230?250 grams of the body weight. The animals were divided into five groups as control, saline (1 ml/kg/day olive oil for 30 days), Wi-Fi (12 h/day for 30 days), melatonin (10 mg/kg/day for 30 days) and melatonin + Wi-Fi (10 mg/kg/day +12 h/day for 30 days). In the thirtieth day, thirty minutes after the last drugs administration at the indicated doses, PTZ in 45 mg/kg was administered to induce epileptic seizure. The animals were observed for 30 min during the seizure stages (according to the Racine Scale) and first myoclonic jerk times (FMJ). Twenty-four hours after PTZ injection, brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis (CA) 1, CA3 and DG (dentate gyrus) regions were histopathologically evaluated in terms of a neuronal damage in addition that oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues.ResultsWi-Fi was not found to affect behavioral changes associated with epilepsy (p > 0.05). However, Wi-Fi reduced anticonvulsive and antioxidant effect of melatonin (p < 0.05). Moreover, Wi-Fi increased neuronal damage in hippocampus (p < 0.05).ConclusionWi-Fi did not directly affect epileptic seizures. Nevertheless, it inhibits the positive effects of melatonin on epilepsy and it also has negative effects on hippocampal neuronal damage. These effects of Wi-Fi may occur via oxidative pathways.     

Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR) and in normal Wistar rats (N = 6/group). The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively). The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40) and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40) for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.     

HMME-PDT对大鼠致龋模型中变形链球菌抑制作用的研究

目的 探讨不同参数光动力疗法(PDT)在大鼠口腔龋齿预防中的作用.方法 用变形链球菌感染Wistar大鼠口腔,建立龋齿模型.以0.9%生理盐水、0.2%氟化钠为对照组,单纯激光、单纯光敏剂、不同参数PDT为实验组.采用血卟啉单甲醚(HMME)为光敏剂,532 nm半导体激光为光源,每周处理牙齿1次,5周后处死大鼠,Ke...     

Low- and high-frequency electric cortical stimulation suppress the ferric chloride-induced seizures in rats

The clinic treatment of epilepsy with epileptic foci overlapped with eloquent cortex is not satisfactory. In this study we investigated the direct effects of low- and high-frequency electric cortical stimulation (ECS) on ferric chloride-induced seizures in the experimental rats. Results showed that spontaneous seizures were observed in all rats during the EEG recording after the intracortical injection of ferric chloride solution into left sensorimotor cortex. One-hertz or 100-Hz ECS with 0.3 ms duration and 0.1 mA amplitude square pulses in 1 h on the cortical lesioned area significantly decreased the number of seizures compared with that of the non-stimulation control group. The mean duration time of seizures in 1-Hz or 100-Hz groups was apparently shorter than that in the control group. In brief, this study showed that both low- and high-frequency ECS suppressed the seizures induced by ferric chloride in rats, indicating their potential treatment effects on epilepsy in clinic.     

Sex differences in fear-induced feeding cessation: prolonged effect in female rats

Fear inhibits food intake. Cessation of eating in anticipation of danger is an adaptive response that prepares an organism for an imminent threat, but it could become maladaptive when persistent. To begin to examine the underlying mechanisms, we developed an animal model for fear-cue induced inhibition of feeding. In that preparation, food-deprived rats stop eating when presented with a tone that signals a foot-shock based on prior associations. Here, we examined whether there are sex differences in adult male and female rats. We found that female rats showed sustained fear-cue induced feeding inhibition compared to males during the extinction. During the first of four extinction tests with tone presentations, both male and female rats showed similar, robust cessation of eating. Rats of both sexes that previously received tone-shock pairings ate significantly less than the control rats that received tones without shocks during training. Male rats extinguished this behavior during the second test, while females continued to show the effect during the second and third tests, and extinguished during the fourth test. The findings provide a novel framework for investigation of sex differences in the control of feeding and the underlying brain substrates. The animal model may also be informative for understanding human eating and associated disorders. In particular, the potential contribution of fear in the maintenance of low food intake in anorexia nervosa is hypothesized.     

Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia

Intramuscular injection of selective NMDA receptor antagonists memantine and arcaine 4-fold decreased the incidence of pentylenetetrazole-induced generalized tonic-clonic seizures in rats, while the incidence of clonic seizures decreased by 1.2–1.3 times. Memantine and arcaine are characterized by low therapeutic index, i.e. induced ataxia in rats in doses exceeding the effective anticonvulsant dose by only 3.5–10 times. Intramuscular injection of IEM-1913 (combined blockade of NMDA and AMPA receptors in the brain) decreased the incidence of pentylenetetrazole-induced clonic and tonic-clonic seizures in rats by 4–8 times. The therapeutic index of IEM-1913 surpassed that of memantine and arcaine by 200–600 times. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 675–677, June, 2008     

柳氮磺胺吡啶对溃疡性结肠炎患者血清IFN-γ、IL-4及黏膜炎症的影响

目的： 探讨柳氮磺胺吡啶（SASP）对溃疡性结肠炎（UC）患者血清干扰素（IFN）-γ、白细胞介素（IL-4)和黏膜炎症的影响。方法： 活动期中度UC患者50例，口服SASP 1 g，每日3次，共6周，应用ELISA法检测血清IFN-γ、IL-4，组织学检测黏膜炎症。结果： 患者治疗前血清IFN-γ为（31.6±4.3) ng/L，显著高于治疗后的(22.3±5.6) ng/L（P<0.05），治疗前IFN-γ明显高于对照组的(17.5±5.9) ng/L（P<0.01）；治疗前IL-4为(4.6±1.8) ng/L，显著低于治疗后的(8.9±2.0) ng/L（P<0.05），治疗前IL-4明显低于对照组的(10.9±2.7) ng/L（P<0.01）。治疗前后嗜酸性粒细胞浸润率分别为100.0%和90.0%（P<0.05），隐窝脓肿分别为48.0%和13.3%（P<0.01），黏膜组织学分级分别为（2.49±0.84）级和（1.31±0.75）级（P<0.01）。结论： SASP能明显逆转中度活动期UC患者的Th1和Th2细胞的失衡状态和UC炎症黏膜的隐窝脓肿，减少中性白细胞和嗜酸性粒细胞的浸润，从而促进炎症黏膜的愈合。     

Mediodorsal thalamic stimulation is not protective against seizures induced by amygdaloid kindling in rats

Deep brain stimulation (DBS) is now emerging as a new option for treating intractable epilepsy. Cumulative studies suggest that the mediodorsal thalamic nucleus (MD) is involved in limbic seizure activity. This study aims to investigate whether DBS of the MD can protect against seizures induced by amygdaloid kindling. We studied the effect of low-frequency stimulation (LFS, 1 Hz) or high-frequency stimulation (HFS, 100 Hz) in the MD on amygdaloid kindling seizures. During the kindling acquisition, DBS in the MD was daily administered immediately after the kindling stimulus or before the kindling stimulus (preemptive DBS). The effects of both post-treatment of DBS and preemptive DBS in the MD on the expression of amygdaloid kindling seizures were evaluated. We found the DBS or preemptive DBS in the MD, either LFS or HFS, did not significantly change the rate of amygdaloid kindling. Similarly, DBS or preemptive DBS in the MD did not significantly change any parameters representing the expression of amygdaloid kindling. Our study suggests that DBS in the MD may have no significant effect on limbic seizures.     

额叶癫痫发作的临床与脑电图特征

目的 :分析额叶癫发作的临床及EEG特征。方法 :经同步录像脑电图 (Video—EEG)监测 ,对 40例癫病人 181次额叶发作的临床表现及EEG进行同步分析。结果 :额叶发作频繁而短暂 ,以睡眠中发作为主。常见的临床表现依次为过度运动、扭转性强直、姿势性强直、发声、假性失神等。发作间期额区棘、尖波稀少且波形不典型 ,发作期额叶限局性或弥漫性的改变与背景活动的差别不明显。结论 :临床和EEG不典型是导致额叶发作临床诊断困难或误诊的主要原因。认识额叶发作的临床特点 ,延长EEG记录时间及发作期临床—EEG同步分析有助于对额叶发作的诊断。     

Carnosine, a precursor of histidine, ameliorates pentylenetetrazole-induced kindled seizures in rat

Carnosine (beta-alanyl-l-histidine) has been characterized as a putative neurotransmitter. However, so far, understanding of the role of carnosine in the brain is very limited. The objective of this study was to examine the effects of carnosine on the development of pentylenetetrazol (PTZ) kindling seizures and protection against the PTZ kindled seizures in rats. Chemical kindling was elicited by repeated intraperitoneal injection of PTZ (35 mg/kg) once every 48 h until the occurrence of Stage 4-5 seizures, and the seizure activity of kindling was recorded for 30 min. In an acute PTZ challenge study, 60 mg/kg PTZ was used to induce kindled seizure. Injection of carnosine (200, 500 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latencies for myoclonic jerks, in a dose- and time-dependent manner. In the seizure development process, 500 mg/kg carnosine also significantly delayed the onset of PTZ kindled seizures. In addition, carnosine significantly reversed decreased histamine levels induced by PTZ kindled seizure in the hippocampus. These results indicate that carnosine can protect against PTZ-induced seizures in both the development of kindling and the challenge process in rats. The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future.     

肾病综合征大鼠模型的建立及酶酚酸酯对其作用的实验研究

目的：研究酶酚酸酯（ＭＭＦ）对大鼠肾病综合征的治疗作用。为临床应用提供依据。方法：经尾静脉一次性注射阿霉素,构建大鼠肾病综合征动物模型。观察ＭＭＦ对大鼠肾病综合征血、尿生化指标、淋巴细胞电压依赖性钾通道及肾脏组织学改变的影响。并与强的松进行对照研究。结果：注射阿霉素１４ｄ。大鼠肾病综合征模型建立。模型鼠表现外周Ｔ淋巴细胞电压依赖性钾通道电流增强。ＭＭＦ治疗可使大鼠尿蛋白和血尿素氮明显下降。血白蛋白上升。肾脏病理显示足突无明显融合。疗效明显优于强的松治疗组。结论：在阿霉素诱导的大鼠肾病综合征模型的形成中,细胞免疫参与了其发病,ＭＭＦ能明显改善模型鼠的肾功能并减轻肾脏组织形态学损害。且疗效优于强的松。