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为了对文冠果油相关产品的开发提供数据支撑，将健康雄性小鼠分为4个组，即对照组（玉米油）、文冠果油低剂量组〔2.1 g/（kg·d）〕、文冠果油中剂量组〔4.2 g/（kg·d）〕和文冠果油高剂量组〔12.5 g/(kg·d)〕，分别经口给予小鼠灌胃1个月后，测定小鼠体质量，并进行跳台试验、避暗试验、水迷宫试验以评价文冠果油对雄性小鼠记忆能力的影响,试验结束后测定小鼠海马和大脑皮质组织匀浆中多巴胺（DA）、5-羟色胺（5-HT）、去甲肾上腺素（NE）、乙酰胆碱（ACh）含量及乙酰胆碱酯酶（AChE）活性,探讨文冠果油对小鼠记忆能力的影响机制。结果表明：经过1个月的灌胃试验，各组小鼠体质量及其增长率均无显著差异；文冠果油组小鼠跳台试验、避暗试验、水迷宫试验均为阳性；文冠果油高剂量组小鼠海马和大脑皮质组织匀桨中5-HT、ACh、NE、DA含量明显升高，AChE活性明显降低。综上，文冠果油具有改善小鼠记忆的功能，且是通过改善单胺类神经递质和胆碱能神经递质的代谢发挥作用的。In order to provide data support for the development of Xanthoceras sorbifolium Bunge. oil related products, healthy male mice were divided into 4 groups, namely control group (corn oil), low-dose group 〔2.1 g/(kg·d)〕, medium-dose group 〔4.2 g/(kg·d)〕 and high-dose group 〔12.5 g/(kg·d)〕 of the Xanthoceras sorbifolium Bunge. oil. After one month of intragastric administration, the body weight of mice was measured, and the step-down test, dark avoidance test and water maze test were carried out to evaluate the effects of Xanthoceras sorbifolium Bunge. oil on memory ability of male mice. In addition, the contents of dopamine (DA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), acetylcholine (ACh) and the activity of acetylcholinesterase (AChE) in the homogenates of hippocampus and cerebral cortex of mice were measured to explore the mechanism of the effect of Xanthoceras sorbifolium Bunge. oil on memory ability of mice. The results showed that there was no significant difference in body weight and growth rate among all groups after one month of intragastric administration test. The step-down test, dark avoidance test and water maze test were all positive. In high-dose group, the contents of 5-HT, ACh, NE and DA in homogenates of hippocampus and cerebral cortex of mice were significantly increased and the activity of AChE was significantly decreased. In summary, Xanthoceras sorbifolium Bunge. oil has the function of improving memory of mice, and it plays the role by improving the metabolism of monoamine neurotransmitters and cholinergic neurotransmitters.

Goal of the current work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide-induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures. Relevance of this study is related to poor understanding of the effects of acute and chronic stress on manifestation of cognitive brain functions, as well as ambiguity of the literature data on the effects of both stresses on hypothalamic pituitary axis and expression of the proinflammatory cytokine genes. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze. For the period of learning, the rats under acute stress swam on average less distance to reach a hidden platform, spent less time in the peripheral zone of the pool (thigmotaxis), and had low speed compared to the control animals and to the group of rats under chronic LPS-induced stress. In the test without a platform in the pool there were no significant differences between the groups on the time spent in the platform quadrant and distance swum. Acute stress caused substantial increase of the TNF-α and IL-1β mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Although chronic stress increased the levels of the TNF-α and IL-1β mRNA in the amygdala and hippocampus compared to the control groups, significance between the groups was only marginal and BDNF concentration did not differ from the control animals in any of the brain structures mentioned. Expression of the IL-6 mRNA only marginally increased in the amygdala of the animals under the acute LPS-induced stress and marginally decreased in the animals under chronic LPS stress in the hippocampus relative to the control groups. In total, the most pronounced molecular-biochemical changes occurred in the amygdala and hippocampus, where increase of the expression of the TNF-α and IL-1β interleukins mRNAs were observed in the animals under acute and chronic LPS-induced stress and no changes in the BDNF mRNA concentration were observed in the frontal lobe. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury. Data Sources: Key terms were “stroke”, “brain diseases”, “brain injuries”, “brain hemorrhage, traumatic”, “acute brain injury”, “dizocilpine maleate”, “dizocilpine”, “MK-801”, “MK801”, “rat”, “rats”, “rattus” and “murine”. PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018. Data Selection: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments. Outcome Measures: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury. Results: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = −58.31, 95% CI: −66.55 to −50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = −1.21, 95% CI: −1.50 to −0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = −10.88, 95% CI: −20.75 to −1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = −1.04, 95% CI: −1.47 to −0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = −58.31, 95% CI: −66.55 to −50.07; P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model. Conclusion: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

BACKGROUND: Human umbilical cord mesenchymal stem cells exert significant neuroprotective effects in animals, including reducing neuronal apoptosis and promoting neuronal regeneration. Current approaches to transfer these cells include transvenous, arterial, lumbar puncture, brain stereotactic transplantation and lateral ventricle transplantation, but all of them are insufficient. OBJECTIVE: To investigate the feasibility and effectiveness of nasal transplantation of human umbilical cord mesenchymal stem cells in the treatment of hypoxic-ischemic brain damage in neonatal rats. METHODS: Ninety 7-day-old Sprague-Dawley rats (provided by the Experimental Animal Center of Shantou University Medical College) were randomly divided into three groups (n=30 per group): in sham operation group the left common carotid artery was only separated and then sutured; in model group, an animal model of hypoxic-ischemic brain damage was prepared through ligation and occlusion of the left common carotid artery combined with hypoxic chamber; in experimental group, the animal model was prepared as described in the model group, and then green fluorescent protein-labeled human umbilical cord mesenchymal stem cells were instilled into the nasal cavity of model rats. Brain tissue was taken 3 days after modeling, and Nissl staining, TUNEL detection, and immunofluorescence staining were performed. The memory and learning abilities of the rats were detected by water maze at 14 and 29 days after modeling. After 14-day water maze test, TUNEL staining of the brain tissue was performed. The animal experiment was approved by the Experimental Animal Ethics Committee of Shenzhen University Health Science Center with the approval No. 2016-121. RESULTS AND CONCLUSION: (1) Nissl staining: Neurons in the cerebral cortex and hippocampal CA1 area of the model group were irregularly arranged, and there were few Nissl bodies. Compared with the model group, the neurons in the cerebral cortex and hippocampal CA1 area were arranged more regularly in the experimental group, and there were more Nissl bodies. (2) TUNEL staining: On 3 and 14 days after modeling, the number of apoptotic cells in the model group was significantly higher than that in the sham operation group (P < 0.05) and in the experimental group (P < 0.05). (3) Immunofluorescence staining: Green-labeled human umbilical cord mesenchymal stem cells were found in the brain tissue of the experimental group, mainly distributed in the hippocampus and cerebral cortex of the injured side. Green fluorescent protein-labeled cells were mainly visible in the injured hippocampus and cortex, but rarely detected in the non-injured brain tissues. Non-GFAP or NSE double staining cells were detected. (4) The average escape latency of the experimental group was lower than that of the model group (P < 0.05). Overall, these findings indicate that nasal transplantation of human umbilical cord mesenchymal stem cells can reduce neuronal apoptosis and improve memory and learning abilities of neonatal rats with hypoxic-ischemic brain damage. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to behavioral and neuroprotective efficacy of Celastrus paniculatus Willd. and Sida cordifolia Linn on hippocampus of the brain in kainic acid induced neurodegenerative diseases. Materials and Methods: A total of 30 albino Wistar rats were randomly divided into five groups: Vehicle control, kainic acid, kainic acid + seed oil of Celastrus paniculatus (SOCP), kainic acid + aqueous root extract of Sida cordifolia (ARESC), kainic acid + SOCP + ARESC. The following was analyzed in all groups: (a) Behavioral tests- Hole board test, Shuttle box test, Morris Water Maze test. (b)Blood parameters- RBC, WBC, Haemoglobin, Platelet count. (c)Serum parametersserum uric acid, serum cortisol, serum cholinesterase. Results: The kainic acid induced Alzheimer rats has shown significant changes towards normal behaviors. Total time spent in the dark chamber, no of head dips, time spent in head dips, latency to head dips, Number of rearing, latency of entrance (Sec) to the platform. The RBC count, platelet count, Hb content has shown a significant increase and WBC count has shown a significant decrease. A significant decrease in the serum cortisol and cholinesterase also shown by the rats treated with SOCP and ARESC as a mark of neuroprotection. Conclusion: SOCP and ARESC could be possibly used as anti-neurodegenerative agents for protecting hippocampus damage caused by kainic acid. However, further studies confirming its potential are certainly warranted. [ABSTRACT FROM AUTHOR]

Cognitive behavior is associated with physiological processes that affect the working performance of an individual. Cognitive control is used to override self-serving impulses and behave in socially desirable manner. The objective of the study is to compare the effects of Choline with Fluoxetine and Clozapine for the modulation of cognitive behavior including learning, memory, locomotor, exploratory behavior and anxiety. The study was based on twenty four albino rats divided into four equal groups: (1) Control kept on normal saline (2) Fluoxetine (3) Clozapine (4) Choline. Morris Water Maze (WM) test was used for the psychological assessment based on neural mechanism involved in spatial learning and memory. Open field activity test evaluated locomotor and exploratory behavior. The behavior modulation in WM test and open field activity test was determined at 1st, 3rd, 5th and 7th week. Fluoxetine, Clozapine and Choline were used as drugs and administered to the rat groups mentioned earlier. The modulation of behavior in WM test and Open field activity test was recorded at 1st, 3rd, 5th and 7th week after administering the drugs. Impairment in learning behavior in Fluoxetine treated group was observed at 1st, 3rd, 5th and 7th week and in Clozapine group at 1st and 2nd week when compared to Control (Saline) group. Rise in latency time was observed in Fluoxetine treated group but was not significant. Clozapine and Choline had exhibited beneficial effects in memory retention and prevention of learning impairment. The findings have led to the conclusion that Choline and Clozapine improve the memory retention after continuous administration of 5 and 7 weeks. Moreover, Clozapine has different receptor specificity as compared to Choline. However, both improve the learning capability and enhance the memory in rats. Meanwhile, Fluoxetine did not show any considerable enhancement of memory. [ABSTRACT FROM AUTHOR]

To observe the effects on spatial long-term memory in the rats with vascular dementia (VD) treated with moxibustion for resolving stasis and promoting meridian circulation. The modified 2-vascular occlusion (2-VO) method was used to prepare VD animal model. The rats were randomized into a sham-operation group, a model group, a moxibustion group and a western medication group, 15 rats in each one. In the moxibustion group, mild warm moxibustion was applied to "Băihuì (百会 GV 20)" "Dàzhuī (大椎 GV 14)" and "Shéntíng (神庭 GV 24)", 20 min at each point, once a day, for 3 weeks consecutively. In the western medicaion group, mouse nerve growth factor (NGF) was injected intraperitoneally, 0.18 mL/kg, once a day, for 3 weeks consecutively. Morris water maze test was used, the time of the first passing platform, the frequency of passing-platform and swimming speed in 120 s were determined of the rats in each group. Western blot were used to test the protein expressions of hippocampal Nestin and DCX. At the end of three courses of treatment, compared with sham-operation group, the difference was not significant statistically in swimming speed in the model group, the moxibustion group and the western medication group separately (all P > 0.05). Three days after modeling, the mean of escape latency was prolonged obviously in the modeled rats compared with the rats in the sham-operation group (88.84 ± 19.94 vs 18.15 ± 9.41, P < 0.01). At the end of three courses of treatment, compared with the sham-operation group(22.01 ± 10.07), the mean of escape latency was different statistically in the model group(89.18 ± 19.70), the moxibustion group(37.21 ± 13.31) and the western medication group separately(51.50 ± 16.15) , all P < 0.01. Compared with the model group, the mean of escape latency was shortened in the moxibustion group and western medication group respectively (37.21 ± 13.31 vs 89.18 ± 19.70, 51.50 ± 16.15 vs 89.18 ± 19.70, both P < 0.01). Compared with the western medication group, there was no statistical significant difference in the mean of escape latency in the moxibustion group (37.21 ± 13.31 vs 51.50 ± 16.15, P > 0.05). Compared with the sham-operation group, the frequency of passing-platform was decreased in the model group (0.73 ± 0.96 vs 2.60 ± 1.45, P < 0.01) ; compared with model group, the frequency of passing-platform was increased in the moxibustion group and the western medicine group and the statistically significant difference presented in the moxibustion group (2.06 ± 1.33 vs 0.73 ± 0.96, P < 0.01). Compared with the sham-operation group, the time of first passing-platform was prolonged in the model group (87.86 ± 33.25 vs 36.13 ± 29.76, P < 0.01). Compared with the model group, the time of first passing-platform was shortened in the moxibustion group and the western medicine group respectively (49.53 ± 29.48 vs 87.86 ± 33.25, P < 0.01; 58.98 ± 36.22 vs 87.86 ± 33.25, P < 0.05). After three courses of treatment, compared with the sham-operation group, Nestin expression was reduced in the model group, (0.33 ± 0.12 vs 0.51 ± 0.02, P < 0.05) and was increased in the moxibustion group and the western medication group respectively (1.33 ± 0.17 vs 0.51 ± 0.02, 1.39 ± 0.10 vs 0.51 ± 0.02, both P < 0.01). Compared with the model group, Nestin expression was increased in the moxibustion group and the western medication group, respectively (1.33 ± 0.17 vs 0.33 ± 0.12, 1.39 ± 0.10 vs 0.33 ± 0.12, both P < 0.01). Compared with the western medication group, the difference was not significant statistically in the moxibustion group (1.33 ± 0.17 vs 1.39 ± 0.10, P > 0.05). After three courses of treatment, compared with the sham-operation group, DCX expression was decreased in the model group, but without significant difference (0.44 ± 0.20 vs 0.51 ± 0.26, P > 0.05), the expression was increased in the moxibustion group and the western medication group respectively (0.98 ± 0.25 vs 0.51 ± 0.26, P < 0.05; 1.11 ± 0.43 vs 0.51 ± 0.26, P < 0.01). Compared with the model group, DCX expression was obviously increased in the moxibustion group and the western medication group (0.98 ± 0.25 vs 0.44 ± 0.20, 1.11 ± 0.43 vs 0.44 ± 0.20, both P < 0.01). The difference in DCX expression was not statistically significant between the western medication group and the moxibustion group (0.98 ± 0.25 vs 1.11 ± 0.43, P > 0.05). Moxibustion apparently improves the long-term memory in VD rats. [ABSTRACT FROM AUTHOR]

Objective To observe the dynamic changes of endothelial progenitor cells (EPCs) in peripheral blood and cognitive ability of rats with different degrees of traumatic brain injury (TBI). Methods A total of 28 male SD rats were randomly divided into 4 groups: sham group, mild traumatic brain injury group, moderate traumatic brain injury group and severe traumatic brain injury group, seven rats in each group. A hole was drilled on the right parietal skull (4.0 mm posterior from bregma and 3 mm lateral to the sagittal suture, hippocampal region) to expose the dura. Rats were subjected to different degrees of traumatic brain injury of 0.9, 2.1, 3.2 atm (1 atm=101.325 kPa). The dynamic changes of EPCs, white blood cell count (WBC) and platelets (PLT) in the circulating blood were measured before (0 h) and after TBI (3, 6, 24, 48, 72, 168, 240 and 336 h after trauma). Morris water maze (MWM) test was performed to record the escape latency and target quadrant change on day 21-25 after TBI in four groups. Results The number of circulating EPCs kept stable throughout the experiment in the sham group. The numbers of EPCs were significantly lower at 3 h after injury in mild, moderate and severe traumatic brain injury groups (17.4±3.1, 15.6±5.0 and 23.6±3.0) than those in the sham group (53.6±7.9, P＜0.05). The numbers of EPCs at 6 h after injury were increased rapidly, and which were significantly higher in the mild and moderate TBI group than those in sham group (P＜0.05). Then the number of EPCs dropped to the normal level on 48 h after injury. The changes of EPCs was inconsistent with the WBC and PLT during the whole experiment. The positioning cruise experiment showed that the escape latency shortened over time in each group. The escape latency was longer in TBI group than that in sham group during the same period. The spatial probe test showed that the percentages of the target quadrant were significantly lower in the moderate and severe TBI groups than those in the sham group and the mild TBI group. Conclusion With the severity of traumatic brain injury, the cognitive ability reduces in model rats. The level of endothelial progenitor cells in circulating blood is related to the severity of the traumatic brain injury, and can be used as a marker to judge the prognosis. [ABSTRACT FROM AUTHOR]

Dynamin 1 is a known synaptic protein, which has is key in the presynaptic regulation of endocytosis. The present study investigated the association between age and the observed changes in Morris water maze performance, and immunoreactivity and protein levels of dynamin 1 in the mouse hippocampal formation. In addition, the effects of dynasore, an inhibitor of dynamin 1, on the hippocampal dependent memory were determined to elucidate the correlation between dynamin 1 and memory. In the training phase of the Morris water maze task, the mean escape latency of the aged group (24 months old) was significantly longer, compared with that of the adult group (4 months old), although the average swimming speed and the total distance traveled during the probe trial were similar in the two groups. In the aged group, the time spent locating the target platform was significantly longer and the time spent in the correct quadrant was significantly shorter, compared with those in the adult group. In the adult group, a moderate level of dynamin 1 was detected in the hippocampal CA1 and CA3 regions, and in the dentate gyrus. In the aged group, the immunoreactivity of dynamin 1 was almost eliminated in the CA3 region and the dentate gyrus. In addition, the protein levels of dynamin 1 in the brain were significantly lower in the aged group, compared with those in the adult group. The direct infusion of dynasore, significantly reduced the contextual memory, compared with that of animals in the vehicle-treated group. These results suggested that dynamin 1 was susceptible to the aging process, and that a reduction in dynamin 1 may result in hippocampal-dependent memory deficits by disrupting endocytosis and the release of neurotransmitters. [ABSTRACT FROM AUTHOR]

This work was performed to test our hypothesis that angiotensin-(1-7) can ameliorate cognitive impairment and cerebrovascular reactivity in 5XFAD mice, a useful model of Alzheimer's disease. 5XFAD mice received intracerebroventricular infusion of (1) vehicle, (2) angiotensin-(1-7), or (3) angiotensin-(1-7)+A779, a specific Mas receptor antagonist, for 4 weeks. Angiotensin-(1-7), through Mas receptor, significantly ameliorated cognitive impairment in 5XFAD mice. As estimated by acetazolamide-induced increase in cerebral blood flow, angiotensin-(1-7), through Mas receptor, enhanced cerebrovascular reactivity in 5XFAD mice. In conclusion, angiotensin-(1-7)/Mas receptor axis improves cognitive function and cerebrovascular function in a mouse model of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Running exercise (RE) improves cognition, formation of anterograde memories, and mood, alongside enhancing hippocampal neurogenesis. Aprevious investigation in a mouse model showed that RE-induced increased neurogenesis erases retrograde memory (Akers et al., 2014). However, it is unknown whether RE-induced forgetting is common to all species. We ascertained whether voluntary REinduced enhanced neurogenesis interferes with the recall of spatial memory in rats. Young rats assigned to either sedentary (SED) or running exercise (RE) groups were first subjected to eight learning sessions in a water maze. A probe test (PT) conducted 24 h after the final training session confirmed that animals in either group had a similar ability for the recall of short-term memory. Following this, rats in the RE group were housed in larger cages fitted with running wheels, whereas rats in the SED group remained in standard cages. Animals in the RE group ran an average of 78kmin 4 weeks. A second PT performed 4 weeks after the first PT revealed comparable ability for memory recall between animals in the RE and SED groups, which was evidenced through multiple measures of memory retrieval function. The RE group displayed a 1.5- to 2.1-fold higher hippocampal neurogenesis than SED rats. Additionally, both moderate and brisk RE did not interfere with the recall of memory, although increasing amounts of RE proportionally enhanced neurogenesis. In conclusion, RE does not impair memory recall ability in a rat model despite substantially increasing neurogenesis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder with observable memory impairment. The present study was performed to evaluate the beneficial effects of lentiviral vector-mediated overexpression of a combination of three transcription regulators, ABN (Ascl1, Brn2 and Ngn2), on learning and memory loss in a mouse model of AD. The AD model was established by injecting Aβ1-42 bilaterally into the mouse hippocampus. Lentiviral ABN was delivered bilaterally into the hippocampus of mice. Animals injected with LV-ABN showed significantly improved spatial learning and memory in the water maze test. Additionally, antibody array analysis indicated that intrahippocampal LV-ABN delivery significantly altered the expression levels of some proteins that were identified as inflammatory factors or neuroprotective and growth factors. In conclusion, our data suggest that LV-ABN delivery can ameliorate spatial learning and memory impairment in an AD mouse model, and the beneficial effect of ABN gene treatment could be linked to inhibition of the neuroinflammatory response and enhancement of neuroprotection and neurogenesis. Thus, these findings indicate that lentiviral ABN gene delivery has potential therapeutic applications for AD. [ABSTRACT FROM AUTHOR]

We examined the efficacy of a Rho kinase inhibitor, Fasudil, on cognitive impairment induced by chronic cerebral hypoperfusion in rats. Thirty-two male adult Sprague-Dawley rats were randomly divided into three groups; treated (T), control (C), and sham-operated (Sh); severe stenosis of the carotid arteries was modeled in the former two groups. During two weeks, 8.35 mg/kg Fasudil and physiological saline were i.p. applied twice per day in the T and C groups, respectively. The Morris water maze test was performed in each group to detect changes in the cognitive function and to observe pathological shifts in hippocampal morphology in rats after eight weeks. The mean escape latency was distinctly shorter ( P < 0.01), and the percentage of swimming distance within the platform quadrant was significantly greater ( P < 0.01) in the T group, compared to those in the C group at the corresponding time points. The rate of carotid artery stenosis in rats demonstrated no statistical difference between the T and C groups ( P > 0.05). Fasudil injections effectively normalized hippocampal pathomorphology in the T group. Thus, the Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats. [ABSTRACT FROM AUTHOR]

Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic5HT-1Areceptors effectiveness. Repeated buspirone administration attenuates 5-HT1A soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone coadministration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD. [ABSTRACT FROM AUTHOR]

The present study investigated the relation of age-dependent spatial learning/memory impairment and Tau phosphorylation in 5XFAD mice, a model of Alzheimer's disease. In the water maze test, the acquisition and retention latencies for 5XFAD mice at 6 months, but not 2 months, of age was significantly longer than those for wild-type mice at the same months of age, without difference in the swim speed and visual acuity between two groups. The level of glycogen synthase kinase 3β (GSK-3β) phosphorylation at Ser9 in the hippocampus for the 5XFAD mice at >4 months of age was significantly lesser than that for wild-type mice at the same months of age, while a robust increase in the Tyr216 phosphorylation of GSK-3β was found both in wild-type and 5XFAD mice at 6 months of age, without no significant difference in the extent between two groups. There was no significant difference in the Tau phosphorylation at Ser202/Thr205 in the hippocampus between two groups, but Ser396 phosphorylation for 5XFAD mice was significantly higher than that for wild-type mice at ages ranging from 2 to 6 months. The results of the present study indicate that Tau hyperphosphorylation in the brain for 5XFAD mice precedes high activation of GSK-3β and occurs in the much earlier stage than appearance of learning and memory disorders. [ABSTRACT FROM AUTHOR]

Liposome-encapsulated hemoglobin with low O2-affinity ( l- LEH) was shown to be protective in focal brain ischemia and reperfusion ( I/ R) in rats and primates. We tested l- LEH in the transient whole brain ischemia in the Tokai high-avoider rat ( THA), which has been selected, mated, and bred over 77 generations for a high and consistent learning ability determined by the Sidman avoidance test ( SAT). Young/naïve (before SAT) and adult/parent (after SAT) THA rats underwent acute and complete four-vessel occlusion in the chest for 3 or 5 min, administration of 2 mL/kg of l- LEH, saline, or homologous washed red blood cells ( RBCs), reperfusion, and resuscitation. One week later, all rats underwent SAT, open-field behavioral observation, Morris water maze tests, and morphological study. Whereas young/naïve rats treated with l- LEH retained a rapid and consistent learning curve as in nonischemic controls, THA rats treated with RBCs or saline had retarded learning response on SAT as well as reduced cellularity in the amygdala. Adult/parent rats with established memory on SAT maintained perfect achievement even after I/ R. In contrast, l- LEH-treated rats showed no better performance on Morris water maze (function) or cellularity of the CA1 sector of the hippocampus (morphology) compared with the rats treated with RBCs. Although task performance on SAT and Morris water maze appeared antithetical, morphological observations corresponded to the respective functions, suggesting that l- LEH was protective only for the amygdala on SAT tasks but not for the CA1 sector of the hippocampus on spatial orientation as in our previous studies on focal brain I/ R, where the cortex was preserved better than basal ganglia. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the systematically rat model of neonatal hypoxic-ischemic brain damage. The right carotid arteries of 7-day-old healthy Wistar rats were ligated, and then, the rats were subjected to an environment with 8 % of oxygen. Four weeks after the birth, neurobehavioral test, water maze test, and motor-evoked potential and neuropathologic examinations were performed. The footprint analysis showed significantly larger and instable paces in the hypoxic-ischemic group ( P < 0.05); the time that rats crossed the balance beam in the hypoxic-ischemic group was longer than the control group ( P < 0.05). The water maze test showed that the escape latency of hypoxic-ischemic group was significantly longer than that of control group ( P < 0.05). The hindlimb quadriceps compound muscle-evoked potential CMEP of rats in hypoxic-ischemic group showed that the wave amplitude was lower than that of control group ( P < 0.05). HE staining showed visible periventricular leukomalacia in hypoxic-ischemic groups; disrupted nuclear membrane was detected in the IH group with transelectronmicroscopy; Immunohistochemistry: compared with control group, MBP-positive neurocytes decreased, glial fibrillary acidic protein positive neurocytes increased in the periventricular zone ( P < 0.05). Carotid artery ligation combining the hypoxic chamber created a reliable and stable rat model of neonatal hypoxic-ischemic brain damage and can be used for experimental research related to management of cerebral palsy. [ABSTRACT FROM AUTHOR]

Abstract: Whether ouabain, a Na+- and K+-activated adenosine triphosphatase inhibitor, mimics cognitive impairments that can be dissociated from motor effects in the bipolar disorder-like animal model remains unclear. Ouabain and the vehicle aCSF were microinjected into the left lateral ventricle immediately, after 4h, and after 24h. The results showed that (a) locomotion responses of the Immediate group were significantly decreased compared to those of the aCSF group, particularly the first five minutes. (b) The ouabain-treated rats have longer latency and total distance traveled in the water maze task; however, the velocity was not affected for the ouabain group. (c) The analysis of covariance showed that the latency time (but not the total distance traveled and velocity) of the ouabain group was more impaired than that of the aCSF group, regardless of omitting total distance traveled and cross movement in the open field test. The latency might be more sensitive than the distance traveled and the velocity for assessing spatial learning. Dissociating the spatial learning from the movement may allow testing drug treatments of cognitive deficits independent of locomotor effects associated with bipolar disorder. [Copyright &y& Elsevier]

The article discusses a study that focuses on designing a relevant new animal model for brain lesions and systematically evaluating the behavioral, cognitive, neuroelectrophysiiological and neuropathological effects in pups subjected to a combined exposure to prenatal inflammation and hypoxia. It suggests that prenatal exposure to lipopolysaccharide following by hypoxic insult led to cerebral white matter changes.

Abstract: Expression of Schaffer collateral-CA1 long-term potentiation (LTP) and long-term depression (LTD) was not affected in hippocampal slices from wild-type mice pretreated with lipopolysaccharide (0.25mg/kg, i.p.), to increase interleukin-18 (IL-18) concentrations in the brain. For IL-18 knock-out (IL-18 KO) mice, the LTP was still expressed, the extent being similar to that for wild-type mice. In the open-field test to assess motor activity, rearing activity for IL-18 KO mice was significantly suppressed as compared with that for wild-type mice, without significant difference in the locomotion activity between two groups. In the passive avoidance test to assess fear memory, the retention latency for IL-18 KO mice was much shorter than for wild-type mice, without significant difference in the acquisition latency between two groups. In the water maze test, the acquisition latency for IL-18 KO mice significantly prolonged as compared with that for wild-type mice, without significant difference in the retention latency between two groups. For IL-18 KO mice, intraventricular injection with IL-18 for 4 days (total, 240fg) prior to water maze task shortened the prolonged acquisition latency, reaching a level similar to that for wild-type mice. The results of the present study, thus, suggest that IL-18 is a critical regulator for exploratory activity, fear memory, and spatial learning. [Copyright &y& Elsevier]

Abstract: 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (1μM) enhanced long-term depression (LTD), a synaptic plasticity relevant to learning and memory, in the CA1 region of rat hippocampal slices, where expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 on the plasma membrane was decreased. In the water maze test, oral administration with POPhtCho (5mg/kg) significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine (1mg/kg), while the acquisition latency was not affected. For humans with mild cognitive impairment and dementia (average of Mini Mental State Examination score, 18), oral intake with POPhtCho (300mg/day, once after breakfast) everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 6 months after intake. The results of the present study, thus, indicate that POPhtCho could ameliorate cognitive disorders, possibly by enhancing LTD. [Copyright &y& Elsevier]

Memory is the ability to store, retrieve and use information that requires a progressive time-dependent stabilization process known as consolidation to be established. The hippocampus is essential for processing all the information that forms memory, especially spatial memory. Neuropeptide Y (NPY) affects memory, so in this study we investigated the participation and recruitment of NPY receptors during spatial memory consolidation in rats. Using the water maze test, we show that NPY (1 pmol) injected into the dorsal hippocampus impaired memory consolidation and that previous restraint stress (30 min) potentiates NPY effects, i.e. further impaired memory consolidation. Using selective antagonists for NPY Y 1 and Y 2 receptors we demonstrate that both receptors play a key role on spatial memory consolidation. Our data suggest that NPY modulates aversive and adaptive memory formation by NPY receptors activation. • NPY (1 pmol) impairs the consolidation of spatial memory in rats. • A previous restraint stress potentiates NPY effects. • NPY Y 1 and Y 2 receptors seem to be recruited during memory consolidation. [ABSTRACT FROM AUTHOR]

Abstract: The leaner mutation in mice affects the Cav2.1 voltage-gated calcium channel α1A-subunit gene (Cacna1a), causing a reduction in calcium currents predominantly in Purkinje cells. This reduction in calcium currents causes severe progressive cerebellar ataxia, beginning around postnatal day 10, in homozygous leaner mice (tg la /tg la ), while their heterozygous littermates (tg la /+) present no obvious behavioral deficits. In humans, heterozygous mutations in the Cacna1a orthologous gene produce a broad range of neurological manifestations. To evaluate the phenotypic status of the tg la /+ animals, we assessed motor performance and cognition, at different ages, in these mutant mice. We were able to observe age-dependent impairment in motor and cognitive tasks; balance and motor learning deficits were found in demanding tasks on the rotarod and on the hanging wire test, while spatial learning and memory impairment was observed in the Morris water maze. Progressive dysfunction in escape reflexes, indicative of neurological impairment, was also present in tg la /+ animals. Although not presenting major motor alterations, tg la /+ mice show age-dependent motor and cognitive deficits. [Copyright &y& Elsevier]

Although Parkinson's disease is a movement disorder, in many patients cognitive dysfunction is an important clinical sign. It is not yet clear whether this is attributable solely to a decrease in dopamine levels, or whether other neurotransmitter systems might be involved as well. In the present study, the importance of the mesocorticolimbic dopamine pathway and a possible convergence with forebrain cholinergic projections to neocortex and hippocampus in the regulation of learning and memory abilities were investigated by using specific lesion paradigms in one or both systems. Lesioning of dopaminergic neurons in the ventral tegmental area resulted in an impaired performance in the reference memory task, whereas the execution of the working memory tasks appeared to be unaffected in the Morris water maze. Analysis of the swim paths revealed that the dopamine-depleted animals were capable of adapting a search strategy on a given testing day but failed to transfer this information to the next day, suggesting a deficit in information storage and/or recall. In contrast, cholinergic lesions alone were without effect in all test paradigms. However, when both dopamine and acetylcholine were depleted, animals were also impaired in the working memory task, indicating that a functional convergence of the inputs from these systems was critical for acquisition of spatial memory. Interestingly, such an additional acquisition deficit appeared only after hippocampal cholinergic depletion regardless of a concurrent disruption of basalocortical cholinergic afferents. Thus, further analyses of cholinergic alterations may prove useful in better understanding the cognitive symptoms in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract: Although stem cells are likely to improve neurological deficits seen after cerebral ischemia, the effects of neural progenitor cells (NPCs) on cerebral ischemia-induced learning dysfunction remain to be clarified. We tested whether the delayed injection of exogenous NPCs could prevent learning dysfunction after cerebral ischemia. Cerebral ischemia was produced by the injection of microspheres into the right hemisphere of each rat. Injection of NPCs obtained from green fluorescent protein transgenic rats into the hippocampus on Day 7 after the induction of cerebral ischemia improved the modified neurological severity score and reduced the prolongation of the escape latency seen in the water maze task. A few of the injected NPCs were positive for mature neuronal markers. In addition, the injected NPCs expressed BDNF on Day 28 after cerebral ischemia. Thus, the exogenous NPCs delivered by injection could act as a source of neurotrophic factors and prevent cerebral ischemia-induced learning dysfunction. [Copyright &y& Elsevier]

The effect of Daikenchuto (DKT), a traditional Japanese herbal medicine (Kampo medicine), and its constituents (ginger rhizome, ginseng root, rice gluten and Zanthoxylum fruit) on the memory formation process was examined in mice by means of a Morris water maze test. The administration of DKT [300–4000 mg/kg, administered orally (p.o.)] for 3 consecutive days dose-dependently shortened the time required by the mice to find the platform in the water maze test relative to the control. Among the four constituents of DKT, the extract of Zanthoxylum fruit (70 mg/kg, the dose equivalent to 4000 mg/kg DKT) administered p.o. for 3 consecutive days significantly promoted the memory and learning rate. The memory- and learning-enhancing effect was potently elicited by 5 mg/kg (p.o., 2 days) hydroxy-sanshool, the active component of the ethyl acetate fraction of Zanthoxylum fruit. In another series of experiments with the water maze test, the administration of scopolamine [1 mg/kg, intraperitoneally (i.p.)] for 3 consecutive days significantly prolonged the time needed by the mice to find the platform. The subsequent administration of DKT (4000 mg/kg, p.o.) for 3 consecutive days possessed an abatement effect on the scopolamine-induced dementia. The present results indicate that DKT and, more specifically, its constituent Zanthoxylum fruit and the active component of Zanthoxylum fruit, hydroxy-sanshool, all have a memory- and learning-enhancing effect and are probably associated with the release of acetylcholine from neuronal terminals in the brain. [ABSTRACT FROM AUTHOR]

Background: In our earlier study, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, facilitated hippocampal synaptic transmission by stimulating glutamate release from presynaptic terminals as mediated via α7 acetylcholine (Ach) receptors under the influence of protein kinase C. The present study assessed the possibility of using DCP-LA as a cognitive enhancer in animal models. Methods: Amyloid-β1−40 peptide (300 pM/day) or saline was continuously injected in the right lateral ventricle of rats for 2 weeks. Then, the water maze test was carried out, once per day for 7 days, 1 h after the intraperitoneal injection with DCP-LA or saline. In a different set of experiments, rats were intraperitoneally injected with scopolamine (1 mg/kg) and the water maze test was performed twice per day, with the first test taking place 1 h after the intraperitoneal injection with DCP-LA, galantamine or saline, and the second test starting 2 min after the end of the first. Results: Continuous intraventricular injection with amyloid-β1−40 peptide in the rat lateral ventricle prolonged the latency for acquisition in the water maze test. DCP-LA (1 mg/kg, intraperitoneal (i.p.)) significantly improved the impairment, which reached a level similar to the latency for sham. Furthermore, DCP-LA (1 mg/kg, i.p.) significantly ameliorated learning and memory deficits in rats treated with scopolamine and was, if not more, effective than galantamine, a modest inhibitor of acetylcholinesterase with nicotinic ACh receptor modulation. Conclusion: The results of the present study show that DCP-LA ameliorates learning and memory deficits induced by amyloid-β1−40 peptide or scopolamine. DCP-LA may thus offer new hope for dementia patients. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) acts as an organotropic factor for regeneration and protection in various organs and has the ability to attenuate cerebral ischemia-induced cell death. However, the effect of HGF on learning and memory function after a cerebral ischemic event is unknown. We demonstrate here that administration of human recombinant HGF (hrHGF) into the ventricle reduced the prolongation of the escape latency in the acquisition and retention tests in the water maze task on days 12–28 after microsphere embolism-induced cerebral ischemia. In addition, disruption of the blood–brain barrier at the early stage after microsphere embolism, which was determined by FITC–albumin leakage, was markedly reduced by treatment with hrHGF. We demonstrated that this effect of hrHGF on the blood–brain barrier was associated with protection against the apoptotic death of the cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF can prevent the learning and memory dysfunction soon after sustained cerebral ischemia by protecting against injury to the endothelial cells. The use of HGF may be a potent strategy for the treatment of cerebrovascular diseases, including cerebral infarct and vascular dementia. [Copyright &y& Elsevier]

We examined whether synaptic plasticity was preserved in aged rats administered an arachidonic acid (AA) containing diet. Young male Fischer-344 rats (2 mo of age), and two groups of aged rats of the same strain (2 y of age) who consumed either a control diet or an AA ethyl ester-containing diet for at least 3 mo were used. In the Morris water maze task, aged rats on the AA diet had tendency to show better performance than aged rats on the control diet. Long-term potentiation induced by tetanic stimulation was recorded from a 300 μm thick hippocampal slice with a 36 multi-electrode-array positioned at the dendrites of CA1 pyramidal neurons. The degree of potentiation after 1 h in aged rats on the AA diet was comparable as that of young controls. Phospholipid analysis revealed that AA and docosahexaenoic acid were the major fatty acids in the hippocampus in aged rats. There was a correlation between the behavioral measure and the changes in excitatory postsynaptic potential slope and between the physiologic measure and the total amount of AA in hippocampus. [Copyright &y& Elsevier]

To investigate the effects of ginsenosides on the memory impairment in Sprague-Dawley rats (SD rats) after anesthesia through the administration of propofol SPF, SD rats were randomly divided into four groups: control group (Group I), propofol-treated group (Group II), low dose of ginsenosides-treated group (Group III) and high dose of ginsenosides-treated group (Group IV). These rats were subjected to fear memory test in shuttle box, Y-maze test and Morris water maze test. Immediately after the test, the expression levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) were further detected by ELISA method. Ginsenosides could ameliorate the impairment on the functions of fear memory, working memory and spatial memory in rats caused by anesthesia via the injection of Propofol. Furthermore, the expression levels of NGF and BDNF on rat hippocampus were significant increased by the treatment of ginsenosides at both two doses compared with the control group (both P < 0.05). Ginsenosides hold potential to be developed as a novel therapeutic agent for those patients suffering from postoperative cognitive dysfunction caused by anesthesia via the treatment of propofol.

Objective: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury., Data Sources: Key terms were "stroke", "brain diseases", "brain injuries", "brain hemorrhage, traumatic", "acute brain injury", "dizocilpine maleate", "dizocilpine", "MK-801", "MK801", "rat", "rats", "rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018., Data Selection: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments., Outcome Measures: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury., Results: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = -1.21, 95% CI: -1.50 to -0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = -10.88, 95% CI: -20.75 to -1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = -1.04, 95% CI: -1.47 to -0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P = 0.004). Further network analysis showed that 0-1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model., Conclusion: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications., Competing Interests: None

Objective: To explore the effect of three kinds of drinking water on learning and memory and hippocampal neurotransmitter of mice., Methods: Water quality parameters, including total dissolved solid( TDS), total hardness, oxygen consumed( OC), sodium, potassium, calcium, magnesium and metasilicic acid, were measured for pure water, tap water and natural mineral water. A total of 60 ICR mice( half male and half female) were randomly divided into three groups and fed with pure water( control group), tap water and mineral water for 90 days. After learning-memory abilities were detected with Morris water maze and passive avoidance test, mice were killed and hippocampi were removed immediately to measure contents of acetylcholine( Ach), nitric oxide( NO), glutamic acid( Glu) and gamma-aminobutyric acid( GABA) and activities of acetylcholinesterase( ACh E), choline acetyltransferase( Ch AT) and total nitric oxide synthase( T-NOS)., Results: Water quality parameters were higher in tap water and natural mineral water than in pure water. On the first day of place navigation test, the escape latency of tap water group [( 69. 15 ± 50. 87) s]was obviously shorter than that of pure water group [( 86. 07 ± 44. 03) s]( P < 0. 05), and mice in tap water group chose effect strategies( 51. 25%) more frequently compared to control mice( 30%)( P <0. 05). In the probe trial, the swimming time of the targeted quadrant was significantly longer in tap water group [( 28. 44 ± 10. 17) s] or mineral water group [( 28. 81 ±12. 43) s] than in pure water group [( 19. 84 ± 9. 59) s ]( P < 0. 05). In passive avoidance test, the training latency and testing latency were significantly longer in tap water group [( 60. 27 ± 57. 84) and( 209. 54 ± 121. 41) s] or mineral water group[( 58. 12 ± 42. 52) and( 271. 40 ± 90. 44) s]than in pure water group [( 10. 99 ± 9. 40)and( 72. 77 ± 67. 51) s ]( P < 0. 05), as the frequency of electric shock and the percentage of animals showing errors in tap water group [( 0. 90 ± 0. 88) times and 50%]or mineral water group [( 0. 10 ± 0. 32) times and 20%]were obviously less than those in pure water group [( 5. 00 ± 4. 62) times and 90% ]( P < 0. 05). Compared with pure water group [( 8. 53 ± 2. 12) μg / mg prot and( 0. 94 ± 0. 49) U / mg prot], a significant increase of Ach concentration and a significant decrease of ACh E activity were observed in tap water group [( 11. 18 ± 3. 46) μg / mg prot and( 0. 41 ± 0. 21) U / mg prot]or mineral water group [( 12. 91 ± 3. 91) μg / mg prot and( 0. 54 ± 0. 28) U / mg prot]( P < 0. 05)., Conclusion: Compared with pure water, long-term drinking tap water or mineral water is more beneficial to learning and memory of mice, and it may be associated with a higher content of hippocampal Ach.

This work was performed to test our hypothesis that angiotensin-(1-7) can ameliorate cognitive impairment and cerebrovascular reactivity in 5XFAD mice, a useful model of Alzheimer's disease. 5XFAD mice received intracerebroventricular infusion of (1) vehicle, (2) angiotensin-(1-7), or (3) angiotensin-(1-7)+A779, a specific Mas receptor antagonist, for 4 weeks. Angiotensin-(1-7), through Mas receptor, significantly ameliorated cognitive impairment in 5XFAD mice. As estimated by acetazolamide-induced increase in cerebral blood flow, angiotensin-(1-7), through Mas receptor, enhanced cerebrovascular reactivity in 5XFAD mice. In conclusion, angiotensin-(1-7)/Mas receptor axis improves cognitive function and cerebrovascular function in a mouse model of Alzheimer's disease.

Animal models of cerebral palsy established by simple infection or the hypoxia/ischemia method cannot effectively simulate the brain injury of a premature infant. Healthy 17-day-pregnant Wistar rats were intraperitoneally injected with lipopolysaccharide then subjected to hypoxia. The pups were used for this study at 4 weeks of age. Simultaneously, a hypoxia/ischemia group and a control group were used for comparison. The results of the footprint test, the balance beam test, the water maze test, neuroelectrophysiological examination and neuropathological examination demonstrated that, at 4 weeks after birth, footprint repeat space became larger between the forelimbs and hindlimbs of the rats, the latency period on the balance beam and in the Morris water maze was longer, place navigation and ability were poorer, and the stimulus intensity that induced the maximal wave amplitude of the compound muscle action potential was greater in the lipopolysaccharide/hypoxia and hypoxia/ischemia groups than in the control group. We observed irregular cells around the periventricular area, periventricular leukomalacia and breakage of the nuclear membrane in the lipopolysaccharide/hypoxia and hypoxia/ischemia groups. These results indicate that we successfully established a Wistar rat pup model of cerebral palsy by intraperitoneal injection of lipopolysaccharide and hypoxia.

Chronic cerebral ischemia is a pathological process in many cerebrovascular diseases and it is induced by long-term hyperlipidemia, hypertension and diabetes mellitus. After being fed a high-fat diet for 4 weeks, rats were subjected to permanent occlusion of bilateral common carotid arteries to establish rat models of chronic cerebral ischemia with hyperlipidemia. Intercellular adhesion molecule-1 expression in rat hippocampal CA1 region was determined to better understand the mechanism underlying the effects of hyperlipidemia on chronic cerebral ischemia. Water maze test results showed that the cognitive function of rats with hyperlipidemia or chronic cerebral ischemia, particularly in rats with hyperlipidemia combined with chronic cerebral ischemia, gradually decreased between 1 and 4 months after occlusion of the bilateral common carotid arteries. This correlated with pathological changes in the hippocampal CA1 region as detected by hematoxylin-eosin staining. Immunohistochemical staining showed that intercellular adhesion molecule-1 expression in the hippocampal CA1 region was noticeably increased in rats with hyperlipidemia or chronic cerebral ischemia, in particular in rats with hyperlipidemia combined with chronic cerebral ischemia. These findings suggest that hyperlipidemia aggravates chronic cerebral ischemia-induced neurological damage and cognitive impairment in the rat hippocampal CA1 region, which may be mediated, at least in part, by up-regulated expression of intercellular adhesion molecule-1.