Sevoflurane reduces ischemic brain injury in rats with diet and streptozotocin-induced diabetes

Abstract

To investigate the role of S100B, oxidative stress and the apoptosis signaling pathways in the sevoflurane induced neuroprotective effect on stroke. The brain injury, molecular and cellular damage, and functional recovery were investigated upon ischemic brain injury followed by sevoflurane treatment. Longa rodent stroke scales was used to quantify neurological deficits. TTC staining was used to measure infarct volume of brain tissue. Absolute brain water content was measured by wet/dry weight method. The neuronal morphological change was assessed by H and E staining. The spatial learning and memory ability were measured by water maze test. Serum proteins including S100B, GSH-PX, SOD, Bcl-2, Bax, Caspase-3 were measured by ELISA. The level of NOS and NO in serum was determined by colorimetric method. Compared with control, the serum proteins including S100B, Bax, NO, Caspase-3, and NOS activity in cerebral infarction rats increased significantly while SOD, GSH-PX, and Bcl-2 decreased significantly. Diabetic mellitus complicated with cerebral infarction rats showed more dramatic increase for S100B, Bax, NO, Caspase-3, and NOS activity and dramatic decrease for SOD, GSH-PX, and Bcl-2. Interestingly, sevoflurane reduced the changes significantly. The S100B level positively correlated with brain damage, NO, Bax, caspase-3, and NOS activity but negatively correlated with SOD, Bax, and GSH-PX. Brain damage in sevoflurane groups decreased while behavior outcomes including Longa neurologic score, learning, and memory increased significantly. The neuroprotective effect of sevoflurane is associated with defense mechanisms against free radical-induced oxidative stress and inhibition of apoptosis. S100B protein correlated with oxidative stress and the apoptosis signaling pathways.     

β-Caryophyllene Attenuates Focal Cerebral Ischemia-Reperfusion Injury by Nrf2/HO-1 Pathway in Rats

This study aimed to identify the effect of β-caryophyllene (BCP) pretreatment and elucidate the Nrf2/HO-1 signaling mechanism after focal cerebral ischemia-reperfusion (I-R) injury in rats. Adult male Sprague–Dawley rats were randomly assigned to the sham-operated group, I-R group and BCP pretreated I-R group. At 24 h after reperfusion, neurological deficits and infarct volume were evaluated. Pathological changes of neuron in hippocampuses were observed by Nissil staining and transmission electron microscopy (TEM). Oxidative stress was assessed by malondialdehyde (MDA) level, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD) and Catalase (CAT) activity. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were analysed by Western blotting and real-time quantitative polymerase chain reaction (Q-PCR). The protein expression of Bcl-2 and Bax was determined by immunohistochemistry. Apoptotic cells were detected using TUNEL staining. In I-R group, neurological deficit scores, cerebral infarct volume, MDA levels, LPO content, NO level, expression of Bax and TUNEL-positive cells were found to be increased at 24 h after I-R injury, while SOD activity, CAT activity and expression of Bcl-2 were decreased. However, results in the BCP pretreatment groups were reversed. And the protein and mRNA expressions of Nrf2 and HO-1 were significantly up-regulated in the BCP pretreated I-R group. Results of Nissil staining and TEM scan manifested that BCP remarkablely improved neuronal injury after I-R in rats. All the above suggested that BCP pretreatment played a neuroprotective role in cerebral I-R injury, which might be exerted by upregulating the expression of Nrf2 and HO-1 to ameliorate oxidative damage and neuronal apoptosis.     

Oxysophoridine Protects Against Focal Cerebral Ischemic Injury by Inhibiting Oxidative Stress and Apoptosis in Mice

Our previous studies have demonstrated that oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation. In this study, we further investigated whether OSR could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. After reperfusion, neurological scores and infarct volume were estimated. Morphological examination of tissues was performed. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Oxidative stress levels were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and Western-blot analysis. OSR pretreatment groups significantly reduced infract volume and neurological deficit scores. OSR decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression. These findings indicate that OSR has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.     

利格列汀对小鼠脑缺血/再灌注损伤的神经保护作用*

目的: 评估二肽基肽酶4(DPP-4)抑制剂利格列汀对小鼠脑缺血/再灌注(I/R)损伤的神经保护作用。方法: BALB/c小鼠随机分为Sham组、I/R组和利格列汀(2.5、5和10 mg/kg) +I/R组,每组均为8只小鼠。不同剂量利格列汀组小鼠均在I/R前3周连续灌胃给药。采用小鼠脑中动脉闭塞(MCAO)1 h诱导I/R损伤模型,再灌注24 h评估神经功能缺损(n=8)和及梗死体积(n=4);再灌注48 h处死小鼠,检测脑组织中谷胱甘肽(GSH)、丙二醛(MDA)、磷酸化肌醇3激酶(PI3K)、磷酸化蛋白激酶 B(p-Akt)和雷帕霉素靶蛋白(mTOR)含量(n=4)。结果: 与I/R组相比,利他列汀预处理组小鼠再灌注24 h后,神经功能缺损评分和梗死体积明显降低(P＜0.05);小鼠再灌注48 h后,脑内MDA含量明显降低(P＜0.05),而GSH、PI3K、p-Akt和mTOR水平明显升高(P＜0.05)。结论: 利格列汀对I/R小鼠具有神经保护作用,可能是通过激活PI3K/AKT/mTOR通路发挥的作用。     

Neuroprotective effect and underlying mechanism of sodium danshensu [3-(3,4-dihydroxyphenyl) lactic acid from Radix and Rhizoma Salviae miltiorrhizae = Danshen] against cerebral ischemia and reperfusion injury in rats

Sodium danshensu (SDSS), the sodium salt of danshensu (DSS), has the same pharmacological effects as DSS. In the present study, we aimed to investigate the neuroprotective effect and possible mechanism of SDSS against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were randomly divided into four groups: sham, control, 30 mg/kg and 60 mg/kg SDSS. Cerebral ischemia was induced by 2 h of middle cerebral artery occlusion (MCAO). Neurological functional deficits were evaluated according to the modified neurological severity score (mNSS); cerebral infarct volume and histological damage were measured by TTC or H–E staining. In addition, the number of apoptotic cells and caspase 3/7 activity were assessed by TUNEL or Caspase-Glo assay. And the expression of apoptosis-regulatory proteins and the PI3K/Akt pathway were investigated by western blotting. Our results showed that treatment with SDSS for 5 days after MCAO remarkably improved neurologic deficits and survival rate, reduced infarct volume and the number of dead neurons. SDSS also decreased the number of apoptotic cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl-2/Bax. Further study revealed that treatment with SDSS also increased the level of p-Akt and p-GSK-3β. Taken together, our results suggest that SDSS has the neuroprotective effect against cerebral I/R injury, and the potential mechanism might to inhibition of apoptosis through activating the PI3K/Akt signal pathway.     

The Neuroprotective Effects of Coccomyxa Gloeobotrydiformis on the Ischemic Stroke in a Rat Model

Stroke is a major cause of mortality and the leading cause of permanent disability. In this study, we adopted the classic middle cerebral artery occlusion(MCAO) stroke model to observe the therapeutic effects of coccomyxa gloeobotrydiformis(CGD) on ischemic stroke, and discuss the underlying mechanisms. Low dose (50 mg/kg.day) and high dose (100 mg/kg.day) concentrations of the drug CGD were intragastrically administrated separately for 8 weeks. Infarct volumes, neurologic deficits and degree of stroke-induced brain edema were measured 24 hours after reperfusion. Furthermore, oxidative stress related factors (SOD and MDA), mitochondrial membrane potential, and apoptosis regulatory factors (mitochondrial Cyt-C, Bcl-2, Bax, and caspase-3) were all investigated in this research. We found that CGD attenuated cerebral infarction, brain edema and neurologic deficits; CGD maintained the mitochondrial membrane potential and decreased mitochondrial swelling. It also prevented oxidative damage by reducing MDA and increasing SOD. In addition, CGD could effectively attenuate apoptosis by restoring the level of mitochondrial Cyt C and regulating the expression of Bcl-2, Bax and caspase 3. These results revealed that CGD has a therapeutic effect on ischemic stroke, possibly by inducing mitochondrial protection and anti-apoptotic mechanisms.     

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。     

The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats

Apoptosis is one of the major mechanisms of cell death during cerebral ischemia and reperfusion injury. Flurbiprofen has been shown to reduce cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanism remains unclear. This study aimed to investigate the potential association between the neuroprotective effect of flurbiprofen and the apoptosis inhibiting signaling pathways, in particularly the Akt/GSK-3β pathway. A focal cerebral ischemia rat model was subjected to middle cerebral artery occlusion (MCAO) for 120 min and then treated with flurbiprofen at the onset of reperfusion. The infarct volume and the neurological deficit scores were evaluated at 24 h after reperfusion. Cell apoptosis, apoptosis-related proteins and the levels of p-Akt and p-GSK-3β in ischemic penumbra were measured using TUNEL and western blot. The results showed that administration of flurbiprofen at the doses of 5 and 10 mg/kg significantly attenuated brain ischemia/reperfusion injury, as shown by a reduction in the infarct volume, neurological deficit scores and cell apoptosis. Moreover, flurbiprofen not only inhibited the expression of Bax protein and p-GSK-3β, but also increased the expression of Bcl-2 protein, the ratio of Bcl-2/Bax as well as the P-Akt level. Taken together, these results suggest that flurbiprofen protects the brain from ischemia/reperfusion injury by reducing apoptosis and this neuroprotective effect may be partly due to the activation of Akt/GSK-3β signaling pathway.     

Echinacoside Alleviates Hypoxic-Ischemic Brain Injury in Neonatal Rat by Enhancing Antioxidant Capacity and Inhibiting Apoptosis

Hypoxic-ischemic brain damage (HIBD) is a leading cause of death and disability in neonatal or perinatal all over the world, seriously affecting children, families and society. Unfortunately, only few satisfactory therapeutic strategies have been developed. It has been demonstrated that Echinacoside (ECH), the major active component of Cistanches Herba, exerts many beneficial effects, including antioxidative, anti-apoptosis, and neuroprotective in the traditional medical practice in China. Previous research has demonstrated that ECH plays a protective effect on ischemic brain injury. This study aimed to investigate whether ECH provides neuroprotection against HIBD in neonatal rats. We subjected 120 seven-day-old Sprague–Dawley rats to cerebral hypoxia–ischemia (HI) and randomly divided into the following groups: sham group, HI group and ECH (40, 80 and 160 mg/kg, intraperitoneal) post-administration group. After 48 h of HI, 2,3,5-Triphenyltetrazolium chloride, Hematoxylin-Eosin and Nissl staining were conducted to evaluate the extent of brain damage. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) production were assessed to determine the antioxidant capacity of ECH. TUNEL staining and Western blot analysis was performed to respectively estimate the extent of brain cell apoptosis and the expression level of the apoptosis-related proteins caspase-3, Bax, and Bcl-2. Results showed that ECH remarkably reduced the brain infarct volume and ameliorated the histopathological damage to neurons. ECH post-administration helped recovering the antioxidant enzyme activities and decreasing the MDA production. Furthermore, ECH treatment suppressed neuronal apoptosis in the rats with HIBD was by reduced TUNEL-positive neurons, the caspase-3 levels and increased the Bcl-2/Bax ratio. These results suggested that ECH treatment was beneficial to reducing neuronal damage by attenuating oxidative stress and apoptosis in the brain under HIBD.

     

姜黄素对癫痫大鼠认知功能障碍的预防作用及其可能机制

目的：探讨姜黄素（curcumin）对癫痫大鼠认知功能障碍的预防作用及其可能机制。方法：将30只成年雄性SD大鼠分为正常对照组、单纯致痫组（SE组）、姜黄素[60mg／（kg·d）]干预组（curcumin组）。采用MorriS水迷宫方法检测大鼠学习记忆功能变化,并检测脑片水平的长时程增强（LTP）变化,处死大鼠后取脑组织并匀浆,测超氧化物歧化酶（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）SE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SE组显著缩短（P〈0．05）。撤离平台后,SE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）,姜黄素治疗后大鼠在平台所在象限的停留时间较SE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,与对照组比较SE组HFS刺激后fEPSP斜率明显减小（P〈0．05）,姜黄素可减轻SE所致的fEPSP斜率减小（P〈0．05）。（3）SE组SOD、GSH—PX、GSH显著下降,MDA明显增高,姜黄素可逆转上述现象,有统计学意义（P〈0．05）。结论：姜黄素可显著减轻癫痫持续状态所致的大鼠认知功能障碍,减轻海马区的氧化应激反应从而保护海马海马是其可能机制之一。     

复方中药提取物对大鼠不同状态下脑组织自由基代谢影响的研究

目的:探讨复方中药提取物对大鼠脑组织自由基代谢和抗氧化系统能力的影响机制。方法:选取70只健康Wistar大鼠,随机分为2组(n=35):对照组(N)和服药组(M)。适应性喂养1周,服药组大鼠连续服用8周的复方中药提取物,9周后将2组大鼠分别于安静状态、定量负荷、力竭运动即刻、力竭恢复12 h、力竭恢复24 h状态下处死。分别测定上述2组大鼠在不同功能状态下脑组织中丙二醛(MDA)含量,谷胱甘肽过氧化物酶(GSH-PX)、还原性谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)活性。结果:五种状态下,服药组MDA含量均显著低于对照组,GSH-PX、GSH、SOD、T-AOC活性均不同程度的高于对照组。结论:复方中药提取物可降低不同功能状态下大鼠脑组织中的MDA含量,提高其脑组织GSH-PX、GSH、SOD、T-AOC活性。     

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。     

Therapeutic effect of Ginkgo biloba polysaccharide in rats with focal cerebral ischemia/reperfusion (I/R) injury

An araban type polysaccharide (GBPw) was purified from the leaves of Ginkgo biloba. The present study aimed to investigate the protective effects of GBPw on focal ischemia/reperfusion (I/R) injury in rat brain. The results of this study demonstrated that GBPw had a positive effect on the rat brain when administered 7 days before focal cerebral I/R injury. This effect was evident with the improvements in neurological deficits, reduction in infarct volume, MDA content and the levels of pro-inflammatory cytokines (TNF-α and IL-1β), and elevation in the SOD and MPO activities and the levels of anti-inflammatory cytokine (IL-10). Thus, the beneficial effects of GBPw on cerebral I/R injury may result from the reduction of oxidative stress and the inhibition of NO production and inflammation induced by I/R. The neuroprotective effects of GBPw supplement may have potential implication in the future for prevention/protection against cerebral ischemic stroke.     

Diel variation in cortisol,glucose, lactic acid and antioxidant system of black sea bass Centropristis striata under natural photoperiod

ABSTRACT

Diel rhythm in activity of antioxidant enzymes, as well as contents of glutathione and lipid peroxides, has been intensively investigated in Mammalia and Aves, however, the relevant studies about fish are few. In the present study, we examined variation in contents of cortisol, glucose and lactic acid in plasma of black sea bass Centropristis striata under natural photoperiod during a 24-h period. In addition, variation in activity of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and glutathione reductase (GR) as well as contents of total glutathione (T-GSH), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in liver and plasma of the fish were also determined. The plasma and liver samples were collected from the test fish at 3 h intervals during a 24-h cycle, with the first sampling time set at 03:00 h. No significant differences were found in glucose content and activities of GSH-PX and GR in plasma, as well as activities of SOD and GR in liver among different sampling times. In contrast, apparent variation was observed in contents of cortisol, lactic acid and MDA in plasma, activities of SOD and CAT in plasma, contents of MDA, T-GSH, GSH and GSSG in liver and activities of GSH-PX and CAT in liver between different sampling times. Moreover, contents of cortisol and MDA in plasma, SOD activity in plasma, and contents of MDA, GSH and GSSG in liver exhibited circadian rhythm, and their acrophases occurred at 06:08 h, 18:38 h, 15:09 h, 09:57 h, 23:36 h and 07:30 h, respectively. The present study indicates that some physiological parameters relating to stress response, such as cortisol and MDA contents in plasma, MDA, GSH and GSSG contents in liver and SOD activity in plasma changed at different time throughout a day in black sea bass. Therefore, caution should be taken when evaluating stress response in fish with these physiological parameters measured at different times.     

丹酚酸A对大鼠脑缺血/再灌注损伤及抗氧化酶活性的影响

目的:探讨丹酚酸A对大鼠脑缺血/再灌注(cerebral ischemia/reperfusion,CI/R)损伤及抗氧化酶活性的影响。方法:采用大鼠脑中动脉闭塞(middle cerebral arteryocclusion,MCAO)2 h再灌注24 h模型。实验终末,检测脑梗死面积,脑水肿以及评价神经功能损伤,并进一步分析脑组织中三种抗氧化酶的活性水平。结果:与模型组相比,丹酚酸A组大鼠脑梗死面积显著减少(P0.05),水肿程度显著减轻(P0.05),神经功能学评分显著下降(P0.05)。模型组再灌注24 h后,SOD,GSH-PX及CAT活性显著下降(P0.05);丹酚酸A组SOD,GSH-PX及CAT活性则显著升高(P0.05)。结论:丹酚酸A对大鼠CI/R损伤具有保护作用,可能与CI/R损伤时的脑组织SOD,GSH-PX及CAT活性显著升高相关。     

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。     

7,8-dihydroxyflavone,a small-molecule tropomyosin-related kinase B (TrkB) agonist,attenuates cerebral ischemia and reperfusion injury in rats

7,8-dihydroxyflavone (7,8-DHF) is a recently identified potent agonist of tropomyosin-related kinase B that can cross the blood–brain barrier after oral or intraperitoneal administration. The aim of the present study was to determine whether 7,8-DHF has neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury and, if so, to investigate the possible underlying mechanisms. Cerebral I/R injury rats were induced by middle cerebral artery occlusion for 90 min followed by reperfusion for 24 h. 7,8-DHF was administered intraperitoneally at a dose of 5 mg/kg immediately after ischemia. Our results showed that 7,8-DHF significantly reduced neurological deficit scores, infarct volumes, and neuronal apoptosis in brains of I/R rats. Meanwhile, 7,8-DHF also increased Bcl-2 expression, decreased expression of cleaved caspase-3, Bax and inducible nitric oxide synthase, and inhibited nuclear factor-κB activation in ischemic cortex. Finally, malondialdehyde and nitric oxide contents were reduced, but activities of glutathione, glutathione peroxidase and superoxide dismutase were restored in ischemic cortex treated with 7,8-DHF. Taken together, our findings demonstrated that 7,8-DHF is able to protect against cerebral I/R injury, which may be, at least in part, attributable to its anti-apoptotic, anti-oxidative and anti-inflammatory actions.     

Neuroprotective effect of Danshensu derivatives as anti-ischaemia agents on SH-SY5Y cells and rat brain

Novel Danshensu derivatives (3–8) were designed and synthesized to improve bioactivity based on the strategy of ‘medicinal chemical hybridization’. Our previous studies indicated that these compounds exhibited noticeable cardioprotective activities. Here, we investigate whether these novel Danshensu derivatives exert neuroprotective activities. An in vitro study revealed that these compounds could increase cell viability and reduce LDH (lactate dehydrogenase) leakage. Moreover, Danshensu-cysteine derivative compounds 6 and 8 could significantly inhibit lipid peroxidation of cell membrane and regulate the expression of apoptosis-related protein (Bcl-2, Bax and caspase 3). An in vivo study demonstrated that treatment with compound 6 at 30 mg/kg markedly decreased the infarct volume of MCAO (middle cerebral artery occlusion) insulted rat brain. Furthermore, treatment with compound 6 showed the antioxidant capacity by increasing the activity of SOD (superoxide dismutase) and GPx (glutathione peroxidase) and decreasing the level of MDA (malondialdehyde) and the ROS (reactive oxygen species) production significantly. These results suggested that these novel conjugates exert significant neuroprotective effects as anti-ischaemia agents and those with high potential merit further investigation.     

维生素E对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨维生素E（VitE）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30只成年雄性SD大鼠随机分为健康对照组、单纯致痫组（SE组）、VitE[按体重100mg／（kg·d）]干预组（VitE组）。采用Morris水迷宫实验方法检测致癫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）SE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）,VitE组寻找平台的潜伏期相对于SE组显著缩短（P〈0．05）。撤离平台后,SE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）,VitE治疗后大鼠在平台所在象限的停留时间较SE组显著延长（P〈0．05）。（2）SE组SOD、GSH—PX、GSH显著下降,MDA明显增高,VitE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：VitE可改善癫痫持续状态后大鼠认知功能,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。