Escin attenuates cerebral edema induced by acute omethoate poisoning

Organophosphorus exposure affects different organs such as skeletal muscles, the gastrointestinal tract, liver, lung, and brain. The present experiment aimed to evaluate the effect of escin on cerebral edema induced by acute omethoate poisoning. Sprague-Dawley rats were administered subcutaneously with omethoate at a single dose of 60?mg/kg followed by escin treatment. The results showed that escin reduced the brain water content and the amount of Evans blue in omethoate-poisoned animals. Treatment with escin decreased the levels of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂) in the brain. Escin also alleviated the histopathological change induced by acute omethoate poisoning. The findings demonstrated that escin can attenuate cerebral edema induced by acute omethoate poisoning, and the underlying mechanism was associated with ameliorating the permeability of the blood–brain barrier.     

Protective effect of reduced glutathione on the liver injury induced by acute omethoate poisoning

Omethoate is an organophosphate insecticide with high toxicity. The aim of this study was to investigate the protective effect of exogenous reduced glutathione (GSH) on omethoate-induced liver injury. Sprague-Dawley rats were randomly divided into three groups: control, OM (omethoate poisoning), and OM+GSH (omethoate poisoning treated with GSH). The activities of acetylcholinesterase (AChE), aspartate aminotransferase (AST), alanine aminotransferase (ALT) in plasma, free organophosphate (FOP) in the liver were determined, and the histopathological changes in the liver were observed. Furthermore, TNF-α and NO in liver homogenate were assayed. The results showed that AChE activity was significantly inhibited by omethoate, but was not altered by GSH treatment. GSH was able to prevent hepatocellular edema and fatty degeneration, decrease liver FOP, attenuate the increased AST and ALT activity, and decline the increase of TNF-α and NO induced by omethoate. These results indicate GSH can attenuate liver injury, and suggest that GSH may be administered to protect the organ from injury in patients with acute organophosphate poisoning.     

脑水肿分子机制的研究进展

脑水肿是指脑内水分增加导致脑容积增大的一种病理现象,是脑组织对各种致病因素的反应。颅内损伤、缺血、缺氧、炎症、脑代谢障碍、肿瘤以及中毒都会引起脑水肿。脑水肿可导致颅内压的升高,当颅内压升高到一定程度时,脑组织就会发生功能和结构的损害,严重者导致脑死亡。先前对脑水肿发病机制的研究包括血脑屏障学说、钙离子学说、脑微循环障碍学说、脑细胞代谢障碍等。但是近年的研究表明脑水肿的发生与水通道蛋白4、基质金属蛋白酶、紧密连接蛋白、炎性细胞因子等密切相关。本文就脑水肿发生的分子机制进行综述。     

Protective effects of Danshensu on liver injury induced by omethoate in rats

This study was to evaluate the protective effects of Danshensu on liver injury induced by omethoate in Sprague Dawley rats. The acute omethoate poisoning model was established by administrating subcutaneously with omethoate at a single dose of 60?mg/kg. Danshensu treatment markedly inhibited the increases of aspartate aminotransferase, alanine aminotransferase, cyclooxygenase-2, tumor necrosis factor-alpha, thromboxane B₂, and thromboxane B₂/6-keto-PGF1alpha ratio induced by omethoate. The histopathological examination further confirmed that administration with Denshensu ameliorated liver injury. The results demonstrated that Danshensu possesses protective action on hepatic injury induced by omethoate and the pharmacological mechanism was related to the anti-inflammatory effect and circulation improvement of Danshensu, at least in part.     

Effects of escin on acute inflammation and the immune system in mice

Escin has been used extensively to treat chronic venous insufficiency, hemorrhoids, and edema resulting from cerebral ischemic damage, trauma or operation. However, no studies have looked at the anti-inflammatory properties of escin administered by intravenous injection, and it is still not clear whether escin has an effect on the immune system. This study seeks to investigate the time dependent anti-inflammatory properties of escin and its effect on the immune system. The anti-inflammatory effect of escin was observed in carrageenan-induced paw edema and acetic acid-induced capillary permeability in mice. The immunopharmacological effects of escin were evaluated by spleen index (SI), thymus index (TI), proliferative capacity of splenocytes (PS), lymphocyte count (LC), serum TNF-α levels, and phagocytic rate (PR) in mice. Escin treatment showed a significant anti-inflammatory effect, similar to that seen with dexamethasone treatment. However, the duration of the anti-inflammatory response was longer with escin treatment than with dexamethasone treatment. The results also demonstrated that escin had no significant effects on SI, TI, LC, PS, TNF-α levels, and PR. The findings suggest that escin is a potent anti-inflammatory drug with long-lasting anti-inflammatory effects and without any immunosuppressive effects.     

七叶皂苷钠对肺部急性炎性渗出的影响

目的：研究七叶皂苷钠对肺部急性炎性渗出的作用。方法：以乙酸所致的腹腔毛细血管通透性增高模型小鼠观察七叶皂苷钠对急性渗出作用的时效关系;以肾上腺素致大鼠急性肺水肿和内毒素致小鼠急性肺损伤模型,观察七叶皂苷钠对急性肺部炎症渗出的影响。结果：七叶皂苷钠抑制急性炎症渗出作用的起效较慢,给药5h后作用开始较为明显,作用可持续24h;预防给药,可明显降低急性肺水肿大鼠的死亡率;对肾上腺素及内毒素所致肺部炎症也有明显抑制作用。结论：七叶皂苷钠可用于急性肺炎中肺部急性炎症渗出的防治。     

依达拉奉联合七叶皂苷钠治疗急性脑出血的临床观察

目的：探讨依达拉奉联合七叶皂苷钠治疗急性脑出血的临床研究。方法将60例急性脑出血患者按数字表法随机分为对照组和观察组,每组各30例。对照组采用常规的内科治疗,观察组在对照组基础上分别给予依达拉奉和七叶皂苷钠静脉滴注。于治疗后14 d、28 d进行神经功能恢复情况,病灶体积,临床疗效评定。结果与对照组相比治疗后14 d、28 d,观察组NIHSS评分明显低于对照组义（ t＝2．136, t＝4.117,P＜0．05,P＜0．01）。治疗后14 d,血肿、水肿差异均无统计学意义（t＝1．395,t＝0．737,均P＞0．05）;治疗后28 d,血肿、水肿差异均有统计学意义（t＝3．140,t＝2．367,P＜0．01,P＜0．05）。两组总有效率差异有统计学意义（χ2＝6．650,P＜0．01）。结论依达拉奉联合七叶皂苷钠治疗脑出血可显著改善患者的神经功能缺损、血肿吸收、临床疗效,安全可靠。     

A novel Na+ and Ca2+ channel blocker, T-477, prevents brain edema following microsphere-induced permanent occlusion of cerebral arterioles in rats

One of the most common acute complications of stroke is brain edema. Treatment of edema is recommended when the condition of the patients is deteriorating. The present study was undertaken to evaluate the effect of T-477 [(R)-(+)-2-(4-chlorophenyl)-2,3-dihydro-4-diethyl aminoacetyl-4H-1,4-benzorthiazine hydrochloride], a novel neuronal Na+ and Ca2+ channel blocker, on brain edema in rats. Cerebral ischemia was induced by intra-arterial infusion of 1000 microspheres into the forebrain of freely moving rats, resulting in brain edema. T-477 was intravenously infused continuously for 24 h or twice for 3 h with a 3-h interval between infusions immediately after microsphere injection. T-477 dose-dependently inhibited the increase in brain water content by both infusion procedures; the inhibition was statistically significant at doses of 25 mg/kg per 24 h and 14 mg/kg per 9 h. Additionally, infusion of T-477 at a dose of 14 mg/kg per 9 h significantly inhibited the decrease in K content and the increase in Ca content of the forebrain. In conclusion, T-477 prevents brain edema following microsphere-induced cerebral embolism in rats.     

蜕皮甾酮对缺血性脑损伤的影响

研究了蜕皮甾酮对抗急性脑缺血作用及对脑缺血再灌注引起的记忆障碍的影响．结果发现：蜕皮甾酮１４４ｍｇ／ｋｇ能对抗小鼠急性脑缺血造成的损伤和由于脑缺血引起的体温下降并改善由于脑缺血再灌注引起的学习记忆障碍．蜕皮甾酮１０ｍｇ／ｋｇ还能改善大鼠脑缺血引起的脑水肿并显著降低脑缺血大鼠脑组织钙含量．表明蜕皮甾酮对缺血性脑损伤具有保护作用     

西宁地区急性重症脑出血昏迷患者应用奥德金治疗的疗效观察

目的：观察奥德金注射液对西宁地区急性重症脑出血昏迷患者的神经功能恢复的疗效。方法：观察80例急性重症脑出血昏迷患者（格拉一斯哥昏迷评分在7～10分之间），随机分为治疗组和对照组各40例，对照组给予甘露醇等常规治疗2周，治疗组在常规治疗的基础上给予奥德金注射液30mL·d^-1，观察两组治疗2周后格拉-斯哥昏迷评分变化、头颅CT血肿量和脑水肿情况及治疗后清醒时间，并对其进行统计分析。结果：两组患者格拉-斯哥昏迷评分及头颅CT血肿量和脑水肿情况治疗前后比较有显著性差异（P〈0．05），治疗后对两组患者格拉-斯哥昏迷评分、头颅CT血肿量和脑水肿情况及清醒时间进行比较，两组间有显著性差异（P〈0．05）。结论：急性重症脑出血昏迷患者尽早应用奥德金可促进血液吸收，减轻脑水肿，缩短昏迷时间，促进神经功能恢复。     

Escin attenuates acute lung injury induced by endotoxin in mice

Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and antiedematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity.     

花椒毒酚抑制大鼠局灶性脑缺血/再灌注损伤后中性粒细胞浸润和脑水肿

目的研究花椒毒酚对大鼠局灶性脑缺血/再灌注损伤后中性粒细胞浸润、细胞粘附分子表达及脑水肿的影响。方法线栓法短暂阻塞大鼠大脑中动脉制备局灶性脑缺血(2 h)再/灌注(24 h)损伤模型,缺血后1 h和12 h两次腹腔注射花椒毒酚2.5、5和10 mg.kg-1,再灌注24 h,检测大鼠神经功能行为缺陷评分、脑水肿和脑梗死范围,分光光度法测定缺血区脑组织中Na+,K+-ATPase、Ca2+-ATPase和髓过氧化物酶(MPO)的活性,免疫组织化学染色测定大脑皮层细胞间粘附分子-1(ICAM-1)和E选-择素(E-selectin)的表达。结果花椒毒酚能改善大鼠脑缺血/再灌注后神经功能行为缺陷评分,减轻脑水肿和降低脑梗死范围,增强Na+,K+-ATPase和Ca2+-ATPase活性,降低脑组织中MPO的活性,抑制ICAM-1和E-selectin表达。结论花椒毒酚对脑缺血/再灌注损伤有保护作用,其机制可能与其抑制炎症反应和减轻脑水肿有关。     

尼莫地平对早期脑出血大鼠AQP4mRNA、MMP-9mRNA表达的影响

目的：探讨尼莫地平对早期脑出血周边组织AQP4mRNA、MMP-9mRNA表达及由脑出血引起的继发性脑水肿与AQP4、MMP-9的关系。方法：制做脑出血大鼠模型,分为假手术组,脑出血组及尼莫地平组,分别观察6h、1d、3d、5d、7d等5个时间点出血周边脑组织含水量、AQP4mRNA、MMP-9mRNA。结果：（1）脑出血组3d含水量达到高峰,第7天明显下降,但仍高于正常水平;尼莫地平组3d含水量达高峰,但低于脑出血组。（2）脑出血组AQP4mRNA、MMP-9mRNA的表达逐渐升高,3d达到高峰,7d明显下降,5个时间点明显高于假手术组。（3）尼莫地平组大鼠脑水肿程度、AQP4mRNA、MMP-9mRNA表达逐渐升高,3d达到高峰,明显低于脑出血组。（4）脑出血的水肿程度与AQP4mRNA、MMP-9mRNA呈正相关。结论：（1）AQP4、MMP-9参与了出血性脑水肿损伤的过程。（2）尼莫地平可以抑制AQP4、MMP-9的表达,进而减轻脑水肿的程度。     

Enzyme studies with human and hen autopsy tissue suggest omethoate does not cause delayed neuropathy in man

Levels of acetylcholinesterase and neurotoxic esterase were measured in brain autopsy material. In tissue from a fatal human poisoning and from hens given 4–8 × unprotected LD₅₀ AChE was highly inhibited and neurotoxic esterase uninhibited. The findings correlate with the inhibitory power of omethoate against these enzymes in vitro. It is concluded that omethoate has negligible potential to cause delayed neuropathy and a published report of human neuropathy due to omethoate is criticised.     

Acute carbon monoxide poisoning in an animal model: the effects of altered glucose on morbidity and mortality

An animal in model which the common carotid artery and the jugular vein serving one side of the brain are occluded by indwelling catheters has been used during the past few years to investigate acute carbon monoxide (CO) poisoning. This article reviews the recent research examining the pattern of changes in blood glucose concentration which results from CO exposure, and the manner in which altered glucose concentration alters neurologic outcome and mortality. At present it appears that either greatly depressed glucose or greatly elevated glucose during and/or after CO exposure increases morbidity and mortality. Cyanide (CN) poisoning, in contrast to CO, produces a different pattern of changes in blood glucose and lactate, and unlike CO, fails to slow cardiac AV conduction and ventricular repolarization. Through the use of magnetic resonance imaging and spectroscopic techniques, cerebral cortical edema and the changes in brain phosphagens have been assessed following CO poisoning in the rat. The published results as well as data from recent pilot studies are discussed in the light of our current understanding of CO toxicology.     

白三烯受体拮抗剂ONO—1078对大鼠局灶性脑缺血的神经保护作用

AIM: To determine whether ONO-1078 (pranlukast), a potent leukotriene receptor antagonist, has neuroprotective effect on focal cerebral ischemia in the rat. METHODS: Focal cerebral ischemia was induced by 30 min of middle cerebral artery (MCA) occlusion and followed by 24 h reperfusion. ONO-1078 (0.003-1.0 mg/kg) or vehicle (saline 1 mL/kg) was ip injected 30 min before MCA occlusion and 2 h after reperfusion. The neurological score, infarct volume, neuron density (in cortex, hippocampus, and striatum), brain edema, and albumin exudation around the vessels were determined 24 h after reperfusion. RESULTS: ONO-1078 slightly improved the neurological deficiency, and dramatically decreased infarct volume and neuron loss which showed a bell shaped dose response effect with highest effect at doses of 0.01-0.3 mg/kg. Enlargement of the ischemic hemisphere and albumin exudation were inhibited at doses of 0.01-1.0 mg/kg. CONCLUSION: ONO-1078 has the protective effect on focal cerebral ischemia in rats, which is partially attributed to the inhibition of brain edema. This may represent a novel approach to the treatment of acute cerebral ischemia with cysteinyl leukotriene receptor antagonists.     

Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

Purpose

In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor.

Methods

Three hours and 24 h after the intoxication with soman (172 μg/kg), the mice were anesthetized with an isoflurane/N₂O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain.

Results

A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication.

Conclusions

The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into the brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.     

油酰乙醇胺在小鼠急性局灶性脑缺血再灌注损伤中的作用及机制

目的研究油酰乙醇胺(OEA)在脑缺血再灌注损伤中的作用及机制。方法线栓法制备小鼠大脑中动脉栓塞模型,缺血90 min后再灌注。应用HPLC-MS/MS方法测定脑组织内OEA的含量。给予OEA(5,10,40 mg/kg,ig)或OEA水解酶抑制剂URB597(1 mg/kg,ig),观察其对小鼠急性脑缺血再灌注损伤的影响。测定脑组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)及过氧化氢酶(CAT)的活性。观察MK886对OEA抗脂质过氧化损伤的影响。结果脑缺血再灌注后6 h,损伤侧脑内OEA含量开始升高,再灌注后24 h升高最明显。脑缺血再灌注后给予OEA(40 mg/kg)或URB597(1 mg/kg)可减少神经功能缺失评分,减小脑梗死体积,减轻脑水肿程度。OEA可减少脑内MDA含量,增加抗氧化酶SOD的活性。OEA这一抗氧化作用可被MK886所取消。结论脑缺血再灌注可增加脑内OEA的含量,OEA通过激动PPARα,减轻脂质过氧化损伤发挥抗脑缺血再灌注损伤作用。     

Inhibition of central angiotensin-converting enzyme with enalapril protects the brain from ischemia/reperfusion injury in normotensive rat

Background and the Purpose of the study

Central Angiotensin Converting Enzyme (ACE) has an important role on cerebral microcirculation and metabolism. However, its role in terms of protecting the brain from ischemic/reperfusion (I/R) injury are debatable. This study evaluated the role of ACE, using enalapril as ACE inhibitor, in protection of the brain from I/R injury during transient focal cerebral ischemia (TFCI) in normotensive rat.

Method

Male Sprague Dawley rats (280–320g) randomly assigned to control ischemic and enalapril pre-treated ischemic groups. Enalapril was injected intraperitoneally 1 h before middle cerebral artery occlusion (MCAO) at the dose of 0.03 or 0.1 mg/kg. Cerebral ischemia was induced by 60 min MCAO followed by 24 hrs reperfusion. After evaluation of neurological deficit scores (NDS) the animal was sacrificed for assessment of cerebral infarction and edema.

Results

TFCI induced cerebral infarctions (283±18 mm³), brain edema (4.1±0.4%) and swelling (9.8±1.5%) with NDS of 3.11±0.36. Non-hypotensive dose of enalapril (0.03 mg/kg) improved NDS (1.37±0.26), reduced cerebral infarction (45%), brain edema (54%) and swelling of the lesioned hemispheres (34%) significantly. However, hypotensive dose of enalapril (0.1 mg/kg) could improve neurological activity (1.67±0.31) and failed to reduce cerebral infarction (276±39 mm³) and swelling (10.4±1.4%).

Conclusion

In the rat model of transient focal cerebral ischemia, inhibition of angiotensin converting enzyme with non-hypotensive doses of enalapril has the benefit of improving neurological activity, reducing cerebral infarction, brain swelling and edema of acute ischemic stroke. Therefore, it is reasonable to conclude that central renin-angiotensin system may participate in ischemic/reperfusion injury of the cerebral cortex.     

依达拉奉对脑出血患者血清白介素-6和基质金属蛋白酶-9水平的影响及疗效分析

目的：探讨依达拉奉对脑出血患者血清白介素-6（IL-6）和基质金属蛋白酶-9（MMP-9）水平的影响及其对脑出血的脑保护机制。方法：高血压性脑出血（ICH）患者100例,随机分为治疗组50例和对照组50例。对照组采用西医常规治疗,治疗组在此基础上加用依达拉奉治疗,连续给药2周。两组均记录NIHSS评分、BI指数,计算治疗前后水肿强度,检测血清NO、IL-6、MMP-9水平。结果：治疗后治疗组水肿程度低于对照组（P〈0.01）,治疗组NIHSS评分明显低于对照组（P〈0.01）,BI评分较对照组明显提高（P〈0.01）,治疗组血清NO、IL-6、MMP-9含量均明显低于对照组（P〈0.01）。结论：依达拉奉具有减轻脑出血后炎症反应、清除自由基、抗脑水肿、保护脑细胞作用。