Impairment In Rat Model Research Articles

Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer's disease.

There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventricular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 mL/kg saline. Behavioral test (the shuttle box test) was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alzheimer's disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer's disease.

帕金森病模型大鼠学习记忆能力变化的观察

[目的]利用Morris水迷宫、避暗箱、穿梭箱检测6-羟多巴胺(6-OHDA)致帕金森病(PD)模型大鼠学习记忆的能力，了解PD除行为障碍外的认知变化，并运用大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量检测的方法来对PD大鼠模型进行检验和评价。[方法]实验分为PD模型组和正常对照组。首先以立体定位单侧纹状体注射6-OHDA法制备PD大鼠模型，2周后腹腔注射阿扑吗啡(APO)诱导转圈，旋转圈数 > 7 r/min的大鼠判定为成功PD模型，并运用大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量检测的方法来对PD大鼠模型进行检验和评价。应用Morris水迷宫测定大鼠的目标象限游泳路程及目标象限游泳时间；采用大鼠避暗箱进行多次测试法，获取并分析明箱观察时间百分比(%)数据；应用大鼠穿梭箱进行穿梭箱被动回避反应，获取并分析主动逃避次数(次)和主动逃避平均时间(秒)。[结果] PD模型组大鼠和正常对照组相比，Morris水迷宫实验中，象限游泳路程显著减少(p < 0.05)，目标象限游泳时间极显著减少(p < 0.01)；避暗箱进行多次测试法中，明箱观察时间百分比(%)明显缩短(p < 0.05)；穿梭箱被动回避反应实验中，主动逃避次数(次)和主动逃避平均时间(秒)均明显减少(p < 0.05)。[结论] 6-OHDA纹状体注射构建的PD大鼠的学习记忆能力明显降低，可以作为研究人类帕金森病性痴呆的模型。 [Aim] To evaluate the learning and memory impairment in rat model of Parkinson disease (PD) which established by injection of 6-hydroxydopamine (6-OH) at different stages with Morris maze, passive avoidance test and active avoidance test. [Methods] Rats were grouped into two: PD model rats and Normal rats. The unilateral stereotaxic intra-striatal single point injection of 6-hydroxy- dopamine (6-OH) was adopted to establish PD model rats. The rats were induced to rotate by in-jecting apomorphine (APO) while 2 weeks after operation, in order to screen the successful PD rat model. The number of rotations for the successful PD model rats is greater than 7 r/min. Measuring the distance and the time that the rats stayed the quadrant of the platform with Morris maze. Application of rats box for the shuttle box passive avoidance response, acquisition and analysis of the number of active escapes and takes the initiative to escape the average time(s). [Results] In Morris maze, PD model rats compared with the normal control rats, quadrant swimming distance decreased significantly (P < 0.05) and the swimming time in target quadrant was reduced (P < 0.01) significantly; passive avoidance test for multiple testing method, camera lucida observation time percentage (%) was significantly shortened (P < 0.05). [Conclusion] The learning and memory ability of PD rats which were constructed by striatal injection of 6-OHDA was significantly reduced, and it can be used as a model for the study of Parkinson’s disease dementia.

Establishment of drug delivery system nanocapsulated with an antioxidant (+)-catechin hydrate and sodium meta borate chelator against sodium fluoride induced oxidative stress in rats

Oxidative stress a major cause of fluoride induced toxicity and mitochondrial impairment in common in experimental rats during chronic exposure of fluoride. Attempts have been made in the present experiment to diminish oxidative damage, combined therapy with (+)-catechin hydrate (an antioxidant) and sodium meta borate (chelator) were used. Fluoride intoxication in rats was performed by using 13mg/kg NaF and both antioxidant CH and chelator SMB were used at a concentration of 8.98μM/kg body weight. Mixture of CH and SMB in free or in PLGA nanocapsule encapsulated form were prepared. The efficacies of those formulations were tested in combating free radical mediated oxidative insult produced by sodium fluoride (NaF). The amalgamated therapy used in this experiment was shown to reduce fluoride levels in liver, brain and kidney from 9.5, 5.5, 6.3μg/g to 4.6, 2, 2.6μg/g, respectively. Our result indicated that the combined chelator and antioxidant therapy in nanocapsulated drug delivery system could provide a projection in combating fluoride induced mitochondrial impairment in rat model.

Pinocembrin alleviates memory impairment in transient global cerebral ischemic rats.

The aim of the present study was to investigate the effect of pinocembrin on cognitive ability impairment in a rat model of transient global cerebral ischemia (TGCI). The TGCI model was established by inducing global cerebral ischemia for 20 min, followed by reperfusion for two weeks. The rats were divided into five experimental groups, including the sham group that were not subjected to ischemia, and four ischemic groups where the rats were exposed to TGCI. The sham and control TGCI groups were administered a vehicle intravenously immediately after reperfusion, while the other three groups were intravenously treated with 1, 5 and 10 mg/kg pinocembrin, respectively. In the present study, neurological scores were analyzed at 0 and 24 h after reperfusion, and the effect of pinocembrin on cognitive ability impairment in the TGCI rat model was investigated using a Morris water maze test. Neuronal loss was observed under an optical microscope with the assistance of Nissl staining. In addition, glial fibrillary acidic protein (GFAP)-positive cells were observed under an optical microscope by an immunohistochemistry assay. Pinocembrin treatment was found to alleviate the cognitive impairments, decrease the neurological scores, diminish neuronal loss in the hippocampus and reduce the number of GFAP-positive cells in the hippocampal CA1 region of the TGCI rats. Therefore, pinocembrin alleviated memory impairment in the TGCI rats.

Protective Effect of FTY720 Against Sevoflurane-Induced Developmental Neurotoxicity in Rats

Sevoflurane, a common used inhaled anaesthetic, induces neuronal apoptosis in preclinical studies and correlates with functional neurological impairment. We investigated whether FTY720, a known sphingosine-1 phosphate (S1P) receptor agonist, could exert neuroprotective effect against sevoflurane-induced neurotoxicity. Neuroprotective effect of FTY720 was evaluated in vitro in hippocampal neuronal cells from neonatal rats and in vivo in rat pups. In vitro cell apoptosis was determined by flow cytometry after exposure to 3% sevoflurane for different period of time, or after 6-h exposure to sevoflurane with the presence of FTY720, SEW2871 (selective S1P1 receptor agonist) or combination of FTY720 and VPC23019 (S1P antagonist). Western blot analysis was performed with hippocampal tissue from rat pups exposed to 3% sevoflurane for 6 h with or without pre-treatment with FTY720 injection. Neurological function tests were also performed with rat pups exposed to 3% sevoflurane for 6 h with or without pre-treatment with FTY720 injection. FTY720, at nanomolar concentration, significantly prevents sevoflurane-induced neuronal apoptosis. SEW2871 showed similar neuroprotective effect to FTY720, whereas VPC23019 abrogated the neuroprotective effect of FTY720 when given together. Western blots results demonstrated that FTY710 significantly preserved the level of phosphorylated ERK1/2, Bcl-2 and Bax. Although anaesthetic treatment did not affect general health and emotional status, sevoflurane-induced cognitive impairment in rat models. Administration of FTY720 at 1 mg/kg significantly attenuated sevoflurane-induced neurocognitive impairment. Although further studies are needed to evaluate the feasibility of clinical usage of FTY720 as neuroprotective agent, the study provides preclinical experimental evidence for the efficacy of FTY720 against sevoflurane-induced developmental neurotoxicity.

Protective Role of S-Nitrosoglutathione (GSNO) Against Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion

Chronic cerebral hypoperfusion (CCH), featuring in most of the Alzheimer's disease spectrum, plays a detrimental role in brain amyloid-β (Aβ) homeostasis, cerebrovascular morbidity, and cognitive decline; therefore, early management of cerebrovascular pathology is considered to be important for intervention in the impending cognitive decline. S-nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier modulating endothelial function, inflammation, and neurotransmission. Therefore, the effect of GSNO treatment on CCH-associated neurocognitive pathologies was determined in vivo by using rats with permanent bilateral common carotid artery occlusion (BCCAO), a rat model of chronic cerebral hypoperfusion. We observed that rats subjected to permanent BCCAO showed a significant decrease in learning/memory performance and increases in brain levels of Aβ and vascular inflammatory markers. GSNO treatment (50 μg/kg/day for 2 months) significantly improved learning and memory performance of BCCAO rats and reduced the Aβ levels and ICAM-1/VCAM-1 expression in the brain. Further, in in vitro cell culture studies, GSNO treatment also decreased the cytokine-induced proinflammatory responses, such as activations of NFκB and STAT3 and expression of ICAM-1 and VCAM-1 in endothelial cells. In addition, GSNO treatment increased the endothelial and microglial Aβ uptake. Additionally, GSNO treatment inhibited the β-secretase activity in primary rat neuron cell culture, thus reducing secretion of Aβ, suggesting GSNO mediated mechanisms in anti-inflammatory and anti-amyloidogenic activities. Taken together, these data document that systemic GSNO treatment is beneficial for improvement of cognitive decline under the conditions of chronic cerebral hypoperfusion and suggests a potential therapeutic use of GSNO for cerebral hypoperfusion associated mild cognitive impairment in Alzheimer's disease.

Inhibition of cPLA2 and sPLA2 Activities in Primary Cultures of Rat Cortical Neurons by Centella asiatica Water Extract

Leaf extract of Centella asiatica has been used as an alternative medicine for memory improvement in the Indian Ayurvedic system of medicine for a long time. Although several studies have revealed its effect in ameliorating the cognitive impairment in rat models of Alzheimer's disease, the molecular mechanism of C. asiatica on neuroprotection still remains unexplained. In this study, we investigated the effects of C. asiatica water extract on activity of subtypes of phospholipase A2 (PLA2) in primary cultures of rat cortical neurons and quantified by HPLC a possible molecule responsible for the activity. The cPLA2 and sPLA2 activities were inhibited in vitro by asiaticoside present in the water extract of C. asiatica. This extract may be a candidate for the treatment of neurodegenerative processes because of its pharmacological activity in the brain and its low toxicity, as attested by its long popular use as a natural product.

Gotu Kola (Centella Asiatica) Extract Enhances Phosphorylation of Cyclic AMP Response Element Binding Protein in Neuroblastoma Cells Expressing Amyloid Beta Peptide

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that shows cognitive deficits and memory impairment. Extract from the leaves of Gotu Kola (Centella Asiatica) have been used as an alternative medicine for memory improvement in Indian Ayurvedic system of medicine for a long time. Although several studies have revealed its effect in ameliorating the cognitive impairment in rat models of AD and stimulating property on neuronal dendrites of hippocampal region, the molecular mechanism of Gotu Kola on neuroprotection still remains to be elucidated. In this study, we report that phosphorylation of cyclic AMP response element binding protein (CREB) is enhanced in both a neuroblastoma cell line expressing amyloid beta 1-42 (Abeta) and in rat embryonic cortical primary cell culture. In addition, the contribution of two major single components to the enhanced CREB phosphorylatioin was examined. Furthermore, inhibitors were applied in this study revealing that ERK/RSK signaling pathway might mediate this effect of Gotu Kola extract. Taken together, we provide a possible molecular mechanism for memory enhancing property of Gotu Kola extract for the first time.

(637): Prefrontal-based decision making impairment in rat models of chronic pain

(637): Prefrontal-based decision making impairment in rat models of chronic pain