1-triacontanol cerotate isolated from Marsilea quadrifolia Linn. safeguards hippocampal CA3 neurons and augments special memory deficit in chronic epileptic rats / Cerotato de 1-triacontanol aislado de Marsilea quadrifolia Linn. protege las neuronas CA3 del hipocampo y mejora el déficit de memoria especial en ratas epilépticas crónicas

SUMMARY: Currently many people with epilepsy do not have seizure control even with the best available medications. Moreover various antiepileptics have adverse cognitive impact with other side effect. Thus, need for new antiepileptic drugs still remains challenge. However, many of the natural components have antiepileptic action and this fact remains scientifically unexplored. This study was designed to check the behavioral and neuro-pathological outcome of 1-Triacontanol cerotate (1TAC), isolated from Marsilea quadrifolia Linn. (MQ) on chronic Pentylenetetrazol (PTZ) kindling model of epilepsy in rats. Two-month-old adult male Wistar rats (n=60) were randomly divided into six groups; Group I (Cage Control), II (Vehicle Control), III (Positive Control), IV (Standard drug treated), V (1TAC: 40 mg/kg) & VI (1TAC: 80 mg/kg). To induce kindling a 35 mg/kg dose of PTZ was injected i.p. in every 48 hrs for 30 days in Group III to VI. Spatial memory performance was tested using Morris water maze, following which brains were further processed for histopathological investigations. Interestingly, 1TAC was able to minimize the loss of pyramidal cells in hippocampal CA3 region. These cellular changes were behaviorally responded as improved special learning and memory, a better spatial navigation and object place configuration. The current study strongly implicates that 1TAC from MQ has potent neuroprotective role and augments special memory deficit in chronic epileptic rats. The isolated component which attenuates spatial memory performance could be beneficial outcome to retain cognitive blunting in chronic epilepsy.

RESUMEN: Actualmente, muchas personas con epilepsia no cuentan con un control adecuado de las convulsiones, incluso con los mejores medicamentos disponibles. Además, varios antiepilépticos tienen un impacto cognitivo adverso además de efectos secundarios. Por lo tanto, la necesidad de nuevos fármacos antiepilépticos sigue siendo un desafío. Sin embargo, muchos de los componentes naturales tienen acción antiepiléptica y este hecho permanece científicamente inexplorado. Este estudio se diseñó para verificar el resultado conductual y neuro-patológico del cerotato de 1-triacontanol (1TAC), aislado de Marsilea quadrifolia Linn. (MQ) en el modelo de epilepsia en ratas del pentilenetetrazol (PTZ) crónico (PTZ). Ratas Wistar adultas de dos meses de edad (n = 60) se dividieron aleatoriamente en seis grupos; Grupo I (Control de jaula), II (Control de vehículo), III (Control positivo), IV (Medicamento estándar de tratamiento), V (1TAC: 40 mg / kg) y VI (1TAC: 80 mg / kg). Para inducir la inflamación se inyectó una dosis de 35 mg / kg de PTZ i.p. en cada 48 horas durante 30 días en los grupos III a VI. El rendimiento de la memoria espacial se probó utilizando el laberinto de agua de Morris, después de lo cual se procesaron los cerebros para investigaciones histopatológicas. Curiosamente, 1TAC pudo minimizar la pérdida de células piramidales en la región CA3 del hipocampo. Estos cambios celulares respondieron de manera conductual como una mejora del aprendizaje especial y la memoria, una mejor navegación espacial y la configuración del lugar del objeto. El estudio actual implica fuertemente que 1TAC de MQ tiene un potente papel neuroprotector y mejora el déficit de memoria especial en ratas epilépticas crónicas. El componente aislado que atenúa el rendimiento de la memoria espacial podría ser un resultado beneficioso para retener la reducción cognitiva en la epilepsia crónica.

Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.

Anchusa italica extract: phytochemical and neuroprotective evaluation on global cerebral ischemia and reperfusion

Abstract Stroke is the third leading cause of mortality and disability in industrial countries. Treatment with herbs with antioxidant properties has been reported to be an alternative to the conventional treatments. This study was conducted to investigate the effect of Anchusa italica extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in the rat. To do so, 50 rats were randomly assigned to five groups; control, sham, ischemia, and 50 or 100 mg/kg of Anchusa italica treated animals. Ischemia was induced by occlusion of carotid artery for 30 minutes. Afterward, behavioral tests and biochemical analyses were conducted. Induction of ischemia/reperfusion caused a decline in learning and passive avoidance memory in rats. Moreover, Anchusa italica caused an increase in learning and improved the passive avoidance memory. Induction of ischemia/reperfusion caused a decrease in the antioxidant capacity of the brain and serum as well as an increase in the malondialdehyde of the brain and serum. Anchusa italica led to an increase in the antioxidant capacity of the brain and serum and decrease in the malondialdehyde of the brain and serum. Overall, because of its protective effects on spatial memory, passive avoidance learning, antioxidant capacity, and lipid peroxidation during ischemia/reperfusion, Anchusa italica might be beneficial in ischemic patients.

[Combination thrapy of hydroalcoholic extract of Pistacia atlantica kurdica and fluvoxamine on spatial memory of immobilization rat]

Background and Objective: Oxidative stress causes disorder in the brain processes including memory. Pistacia atlantica kurdica [pistachio] contains antioxidant compounds, oleic and linoleic acid. Fluvoxamine is an antidepressant medicine which inhibits serotonin reuptake. This study was done to determine the effect of hydroalcoholic extract of pistachio and fluvoxamine on spatial memory of male rats under immobilization stress

Methods: This experimental study was done on 30 adult male Wistar rats in 5 groups [n=6]. The control group was not under immobilization stress. Animals in the stress group were just under immobilization stress. Animals in the pistachio group were under immobilization stress and were received 400 mg/kg/bw hydroalcoholic extract of pistachio. Animals in the fluvoxamine group under immobilization stress were received 120 mg/kg/bw fluvoxamine. Animals under immobilization stress, in the pistachio plus fluvoxamine group were received 400 mg/kg/bw hydroalcoholic extract of pistachio and fluvoxamine 120 mg/kg/bw. The radial arm maze test was used for evaluation of spatial memory. After the animals' decapitation, the malondialdehyde and catalase level in hippocampus and the serum level of corticosterone and blood glucose were measured

Results: The stress significantly increased the time of reaching to target, malondialdehyde, corticoestron and blood glucose level, and reduced the catalase in stress group in comprasion with controls [P<0.05]. In the pistachio and the pistachio+fluvoxamine treated groups, the time of reaching to target, malondialdehyde, corticoestron and blood glucose level significantly reduced and the catalase level significantly increased in comprasion with stress group [P<0.05] but fluvoxamine significantly increased the time of reaching to target, malondialdehyde and blood glucose, and reduced the corticoestron and catalase in compared to controls [P<0.05]

Conclusion: The immobilization stress led to attenuation of spatial memory and the fluvoxamine administration as an antidepressant drug caused to deterioration of memory,while the treatment with pistachio extract lead to improve the memory

Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

[Protective effects of Desmopressin acetate on retention of spatial memory deficits induced by post-traumatic stress disorder in Rats]

Post-traumatic stress disorder [PTSD] impairs spatial learning and memory. Desmopressin acetate ameliorates the cognitive deficits induced by electroconvulsive shock. This study was designed to evaluate the protective effects of Desmopressin acetate on retention of spatial memory deficits induced by post-traumatic stress disorder in rats. In this experimental study twenty one male Wistar rats were used. Animals were trained for 5 consecutive days in Morris water maze and then were randomly assigned in three groups [Vehicle + Sham, Saline + PTSD and Desmopressin acetate + PTSD] and tested in a probe 60 sec in 24h after the last acquisition trial. The groups of PTSD+Desmopressin acetate rats and vehicle+sham, saline+PTSD were injected Desmopressin acetate [10 micro gr/kg body weight] and saline [IP], respectively. Injections performed ten minute prior to PTSD and spatial memory was tested ten minutes later. Data were analyzed using SPSS-16, One-Way ANOVA and Tukey tests. The platform location latency of the Desmopressin acetate+PTSD group was significantly shorter [4.24 sec] than the control group [P<0.05] and also, had significantly smaller average proximity values [33.87 cm] compared to the saline+PTSD group [P<0.05]. Desmopressin acetate + PTSD spent significantly more time [21.65%] in the target zone [P<0.05]. This study indicated that Desmopressin acetate blocks the ability of PTSD to impair spatial memory retention