红景天苷对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的:探讨红景天苷(Sal)对癫痫大鼠认知功能障碍的治疗作用及其可能机制。方法:将24只成年雄性SD大鼠随机分为健康对照组、模型组、Sal[按体重1g/(kg·d)]干预组。采用Morris水迷宫方法检测大鼠学习记忆功能变化,并检测大鼠脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)和谷胱甘肽(GSH)、丙二醛(MDA)相应的比酶活力及含量变化。结果:(1)模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),Sal组寻找平台的潜伏期相对于模型组显著缩短(P<0.05)。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长(P<0.05)。(2)模型组SOD、GSH、GSH-PX显著下降,MDA明显增高,Sal干预组SOD、GSH、GSH-PX明显增高,而MDA显著下降,有统计学差异(P<0.05)结论:Sal可减轻癫痫持续状态所致的认知功能障碍,其可能机制是通过减轻海马区氧化应激减轻海马区的损伤,进而改善认知功能。     

红景天苷对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨红景天苷（sal）对癫痫大鼠认知功能障碍的治疗作用及其可能机制。方法：将24只成年雄性SD大鼠随机分为健康对照组、模型组、Sal[按体重1g／（kg·d）]干预组。采用Morris水迷宫方法检测大鼠学习记忆功能变化,并检测大鼠脑组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）和谷胱甘肽（GSH）、丙二醛（MDA）相应的比酶活力及含量变化。结果：（1）模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,Sal组寻找平台的潜伏期相对于模型组显著缩短（P〈0．05）。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长（P〈0．05）。（2）模型组SOD、GSH、GSH—Px显著下降,MDA明显增高,Sal干预组SOD、GSH、GSH—PX明显增高．而MDA显著下降,有统计学差异（P〈0．05）。结论：Sal可减轻癫痫持续状态所致的认知功能障碍,其可能机制是通过减轻海马区氧化应激减轻海马区的损伤,进而改善认知功能。     

Piracetam Improves Cognitive Deficits Caused by Chronic Cerebral Hypoperfusion in Rats

Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.     

红景天苷对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制

目的:探讨红景天苷(Sal)对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制。方法:将30只成年雄性SD大鼠随机分为健康对照组、模型组(Model组)、Sal[按体重1g/(kg.d)]治疗组(sal组)。采用Morris水迷宫实验方法检测缺氧后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽(GSH)、丙二醛(MDA)的水平。结果:(1)模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),Sal组寻找平台的潜伏期相对于模型组显著缩短(P<0.05)。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长(P<0.05)。(2)模型组SOD、GSH-PX、GSH显著下降,MDA明显增高,Sal干预组SOD、GSH-PX、GSH显著增高,而MDA明显下降,具有统计学意义(P<0.05)。结论:Sal可改善高原缺氧大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。     

红景天苷对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨红景天苷（Sal）对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制。方法：将30只成年雄性SD大鼠随机分为健康对照组、模型组（Model组）、Sal[按体重1g／（kg·d）]治疗组（sal组）。采用Morris水迷宫实验方法捡测缺氧后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、谷胱甘）lk（GSH）、丙二醛（MDA）的水平。结果：（1）模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,Sal组寻找平台的潜伏期相对于模型组显著缩短（P〈0．05）。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长（P〈0．05）。（2）模型组SOD、GSH—PX、GSH显著下降,MDA明显增高,Sal干预组SOD、GSH．PX、GSH显著增高,而MDA明显下降,具有统计学意义（P〈O．05）。结论：Sal可改善高原缺氧大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。     

Tetramethylpyrazine Attenuates Cognitive Impairment Via Suppressing Oxidative Stress,Neuroinflammation, and Apoptosis in Type 2 Diabetic Rats

Cognitive dysfunction is an important complication observed in type 2 diabetes mellitus (T2DM) patients. Tetramethylpyrazine (TMP) is known to exhibit anti-diabetic and neuroprotective properties. Therefore, the present study aimed to investigate the possible therapeutic effects of TMP against type 2 diabetes-associated cognitive impairment in rats. High-fat diet (HFD) followed by a low dose of streptozotocin (35 mg/kg) was used to induce diabetes in Sprague–Dawley rats. TMP (20, 40, and 80 mg/kg) and Pioglitazone (10 mg/kg) were administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NOR) tests were used to assess memory function. Fasting blood glucose (FBG), lipid profile, HOMA-IR, glycosylated hemoglobin (HbA1c), and glucose tolerance were measured. Acetylcholinesterase (AChE) and choline acetytransferase (ChAT) activity, acetylcholine (ACh) levels, oxidative stress, apoptotic (Bcl-2, Bax, caspase-3), and inflammatory markers (TNF-α, IL-1β, and NF-kβ) were assessed. BDNF, p-AKT, and p-CREB levels were also measured. In the present work, we observed that treatment of diabetic rats with TMP alleviated learning and memory deficits, improved insulin sensitivity, and attenuated hyperglycemia and dyslipidemia. Furthermore, treatment with TMP increased BDNF, p-Akt, and p-CREB levels, normalized cholinergic dysfunction, and suppressed oxidative, inflammatory, and apoptotic markers in the hippocampus. Collectively, our results suggest that the TMP may be an effective neuroprotective agent in alleviating type 2 diabetes-associated cognitive deficits.

     

Compromised Wound Healing in Ischemic Type 2 Diabetic Rats

Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.     

Intracardiac Injection of Dental Pulp Stem Cells After Neonatal Hypoxia-Ischemia Prevents Cognitive Deficits in Rats

Neonatal hypoxia-ischemia (HI) is associated to cognitive and motor impairments and until the moment there is no proven treatment. The underlying neuroprotective mechanisms of stem cells are partially understood and include decrease in excitotoxicity, apoptosis and inflammation suppression. This study was conducted in order to test the effects of intracardiac transplantation of human dental pulp stem cells (hDPSCs) for treating HI damage. Seven-day-old Wistar rats were divided into four groups: sham-saline, sham-hDPSCs, HI-saline, and HI-hDPSCs. Motor and cognitive tasks were performed from postnatal day 30. HI-induced cognitive deficits in the novel-object recognition test and in spatial reference memory impairment which were prevented by hDPSCs. No motor impairments were observed in HI animals. Immunofluorescence analysis showed human-positive nuclei in hDPSC-treated animals closely associated with anti-GFAP staining in the lesion scar tissue, suggesting that these cells were able to migrate to the injury site and could be providing support to CNS cells. Our study evidence novel evidence that hDPSC can contribute to the recovery following hypoxia-ischemia and highlight the need of further investigation in order to better understand the exact mechanisms underlying its neuroprotective effects.     

Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.     

2型糖尿病大鼠主动脉硬化模型的构建

目的:建立自发2型糖尿病大鼠主动脉硬化动物模型.方法:用2型糖尿病大鼠主动脉硬化动物模型,44只GK大鼠随机分为正常GK对照组、建模组,每组22只,正常Wistar大鼠组22只.期间观察大鼠血糖、尿糖及一般情况变化,8周后,测定各组动物空腹血糖、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、低密度脂蛋白胆固醇(low density lipoprotein choleste rol,LDL-C),同时光学显微镜观察主动脉结构.结果:模型组大鼠的总胆固醇、甘油三酯、低密度脂蛋白胆固醇明显升高,出现主动脉肥大,病理显示明显的主动脉及动脉内膜病变.结论:通过高脂、一氧化氮合成酶抑制剂,可成功构建自发2型糖尿痛大鼠主动脉病变,用作2型糖尿病大鼠大血管病变研究的动物模型.     

姜黄素对高原缺氧大鼠认知功能障碍的预防作用

目的：探讨姜黄素（curcumin）对高原缺氧大鼠认知功能障碍的预防作用。方法：将30只成年雄性SD大鼠随机分为健康对照组、模型组（Model组）、姜黄素【按体重60mg／（kg·d）】治疗组（curcumin组）。采用Morris水迷宫实验方法检测缺氧后大鼠学习记忆功能变化,同时检测脑片水平的LTP变化。结果：（1）模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,姜黄素组寻找平台的潜伏期相对于模型组显著缩短（P〈0．05）。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,姜黄素干预后大鼠在平台所在象限的停留时间较模型组显著延长（P〈0．05）。（2）给予HFS刺激后各组兴奋性突出后电位（fEPSP）斜率较前明显增加,均可持续1h以上,与模型组比较缺氧组HFS刺激后fEPSP斜率明显减小（P〈0．05）,姜黄素可减轻缺氧所致的fEPSP斜率减小（P〈0．05）。结论：姜黄素可改善慢性缺氧大鼠认知功能障碍,但其具体机制尚有待于进一步研究。     

An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats

Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD) on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment.     

姜黄素对高原缺氧大鼠认知功能障碍的预防作用

目的:探讨姜黄素(curcumin)对高原缺氧大鼠认知功能障碍的预防作用。方法:将30只成年雄性SD大鼠随机分为健康对照组、模型组(Model组)、姜黄素[按体重60mg/(kg.d)]治疗组(curcumin组)。采用Morris水迷宫实验方法检测缺氧后大鼠学习记忆功能变化,同时检测脑片水平的LTP变化。结果:(1)模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),姜黄素组寻找平台的潜伏期相对于模型组显著缩短(P<0.05)。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),姜黄素干预后大鼠在平台所在象限的停留时间较模型组显著延长(P<0.05)。(2)给予HFS刺激后各组兴奋性突出后电位(fEPSP)斜率较前明显增加,均可持续1h以上,与模型组比较缺氧组HFS刺激后fEPSP斜率明显减小(P<0.05),姜黄素可减轻缺氧所致的fEPSP斜率减小(P<0.05)。结论:姜黄素可改善慢性缺氧大鼠认知功能障碍,但其具体机制尚有待于进一步研究。     

2型糖尿病模型GK大鼠骨形态学和生物力学特点观察

目的观察2型糖尿病模型GK大鼠的骨代谢特点以及骨密度和骨生物力学特性的变化。方法采用雄性6月龄GK大鼠10只,以月龄、性别匹配的健康Wistar大鼠作为正常对照。颈静脉取血检测与骨代谢有关的生化指标。DXA法测定股骨和腰椎骨密度,并行股骨三点弯曲实验和腰椎压缩实验。甲基丙烯酸甲酯包埋胫骨干骺端以制备不脱钙骨切片。应用多媒体病理图像分析软件进行骨组织形态计量学分析。结果GK大鼠体重明显低于健康对照Wistar大鼠（P〈0.01）。与对照组相比,GK大鼠血清骨钙素水平明显降低[（4.97±0.49,6.75±0.71）μg/mL,P〈0.01],而抗酒石酸酸性磷酸酶活性明显升高[（17.92±5.23,8.31±2.69）U/L,P〈0.01],但血钙和血磷无明显变化（P〉0.05）;股骨和腰椎骨密度显著降低[（0.16±0.01,0.22±0.02;0.12±0.01,0.16±0.02）g/cm2,P〈0.01];骨强度和腰椎的弹性模量明显降低（P〈0.01）。骨形态学分析显示GK大鼠股骨长度和第五腰椎高度分别降低10.3%和9.5%（P〈0.01）,股骨和腰椎横截面积无明显变化（P〉0.05）。骨组织形态计量学分析显示,GK大鼠骨小梁体积、骨小梁厚度、类骨质表面和厚度明显降低[（15.72±1.18,19.13±1.13）%,（61.91±4.54,74.43±3.63）μm,（18.18±1.25,19.63±1.07）%,（3.68±0.48,4.34±0.35）μm,P〈0.01或0.05],动态参数如矿化表面、矿化沉积率和骨形成率也明显降低[（17.77±1.54,19.56±2.07）%,（1.07±0.22,1.35±0.16;0.20±0.03,0.26±0.04）μm/day,P〈0.05或0.01],而矿化延迟时间显著延长（2.66±0.56,2.12±0.35,P〈0.05）。结论非肥胖的GK大鼠表现有骨量减少和骨折危险性增加;2型糖尿病本身可干扰成骨细胞功能和活性而导致骨重建失衡。     

Anti-hyperglycemic Activity of Chromium(III) Malate Complex in Alloxan-Induced Diabetic Rats

The synthesis, characterization, anti-hyperglycemic activity, oxidative DNA damage capacity, and acute toxicity of chromium(III) malate complex [Cr₂(LMA)₃] were described. [Cr₂(LMA)₃] was synthesized in a single-step reaction by chelating chromium(III) with L-malic acid in aqueous solution. Based on elemental analysis, thermodynamic analysis, and spectroscopy studies, the molecular formula of [Cr₂(LMA)₃] was inferred as Cr₂(C₄H₄O₅)₃·5H₂O. Daily treatment with 2.85–17.10 mg/kg body mass of [Cr₂(LMA)₃] in alloxan-induced diabetic rats for 2 weeks indicated that low-molecular-weight organic chromium complex [Cr₂(LMA)₃] had better bioavailability and more beneficial influences on the improvement of controlling blood glucose, serum lipid, and liver glycogen levels compared with CrCl₃·6H₂O. [Cr₂(LMA)₃] did not cause oxidative DNA damage under physiologically relevant conditions. Acute toxicity studies revealed no-measurable toxicity of the [Cr₂(LMA)₃]. Collectively, these results suggest that [Cr₂(LMA)₃] may represent a novel, proper chromium supplement with potential therapeutic value to control blood glucose and serum lipid in diabetes.     

Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury

Aims

To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery.

Materials and Methods

In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury.

Results

Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion.

Conclusion

Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.     

Excessive Activation of NMDA Receptors Induced Neurodevelopmental Brain Damage and Cognitive Deficits in Rats Exposed to Intrauterine Hypoxia

Intrauterine hypoxia is one of the most common stressors in fetuses, which can lead to abnormal brain development and permanent neurological deficits in adulthood. Neurological disorder excitotoxicity induced by hypoxia or ischemia may involve N-methyl-d-aspartate receptors (NMDARs), which are known to participate in the maturation and plasticity of developmental neurons. Inhibition of NMDARs has been reported to improve neurological outcomes in traumatic brain injuries and Alzheimer’s disease. Here, we investigated if antenatal blockade of NMDARs induced by memantine could alleviate neurodevelopmental brain damage and long-term cognitive deficits in intrauterine hypoxia rats. Pregnant rats were assigned to four groups: air control, air?+?memantine, hypoxia, and hypoxia?+?memantine. The rats were exposed to hypoxic conditions (FiO₂?=?0.095–0.115) for 8 h/day (hypoxia group) or given a daily memantine injection (5 mg/kg, i.p.) before hypoxia exposure from pregnant day 19 (G19) to G20 (hypoxia?+?memantine group).The influence of NMDARs antenatal blockade by memantine on intrauterine hypoxia-induced brain developmental damage and cognitive function was then studied. Intrauterine hypoxia resulted in decreased fetal body weight, brain weight, cognitive function, hippocampal neuron numbers, and Ki-67 proliferation index in the hippocampus. Memantine preventive treatment in pregnant rats before hypoxia exposure alleviated the aforementioned damage in vivo. Excessive activation of NMDARs contributes to fetal brain developmental damage and cognitive ability impairment induced by intrauterine hypoxia, which could be alleviated by antenatal memantine preventative treatment.