Brain free fatty acids, edema, and mortality in gerbils subjected to transient, bilateral ischemia, and effect of barbiturate anesthesia

Brain free fatty acids (FFAs) and brain water content were measured in gerbils subjected to transient, bilateral cerebral ischemia under brief halothane anesthesia (nontreated group) and pentobarbital anesthesia (treated group). Mortality in the two groups was also evaluated. In nontreated animals, both saturated and mono- and polyunsaturated FFAs increased approximately 12-fold in total at the end of a 30-min period of ischemia; during recirculation, the level of free arachidonic acid dropped rapidly, while other FFAs gradually decreased to their preischemic levels in 90 min. In treated animals, the levels of total FFAs were lower than the nontreated group during ischemia, but higher at 90 min of reflow, and the decrease in the rate of free arachidonic acid was slower in the early period of reflow. Water content increased progressively during ischemia and recirculation with no extravasation of serum protein, but the values were consistently lower in the treated group. None of the nontreated animals survived for 2 weeks; in contrast, survival was 37.5% in the treated group. It is suggested that barbiturate protection from transient cerebral ischemia may be mediated by the attenuation of both membrane phospholipid hydrolysis during ischemia and postischemic peroxidation of accumulated free arachidonic acid.     

Transient Formation of Superoxide Radicals in Polyunsaturated Fatty Acid-Induced Brain Swelling

The involvement of superoxide free radicals and lipid peroxidation in brain swelling induced by free fatty acids has been studied in brain slices and homogenates. The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3), arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in superoxide and membrane lipid peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect. Furthermore, superoxide formation was stimulated by NADPH and scavenged by the addition of exogenous superoxide dismutase in cortical slice homogenates. These in vitro data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the mechanism of polyunsaturated fatty acid-induced brain edema.     

Characterization of fumonisin toxicity in orally and intravenously dosed swine

Fumonisin B₁ (FB₁), a recently identified mycotoxin produced by Fusarium moniliforme in corn, has been shown to cause death in swine due to pulmonary edema, an apparently species specific effect, and to interfere with sphingolipid metabolism in vitro. Here we characterize the toxicity of fumonisins, using female cross-bred swine weighing 6 to 13 kg, and present a hypothesis regarding the mechanism of fumonisin-induced pulmonary edema in swine. FB₁ was given daily intravenously (IV) to pig 1 for 9 days for a total of 72 mg (7.9 mg/kg) and to pig 2 for 4 days for a total of 67 mg (4.6 mg/kg). Pig 3 (control) was given saline IV for 9 days. Corn screenings naturally contaminated with FB₁ (166 ppm) and FB₂ (48 ppm) were fed to pigs 4, 5, and 6, and ground corn was fed to pigs 7 and 8 (controls). Pigs 4 and 7 were killed on day 5; pig 5 was found dead on day 6; and pigs 6 and 8 were killed on day 15. Pigs 4 and 5 had ingested 187 and 176 mg total fumonisins, respectively, while pig 6 had ingested 645 mg. Feed consumption had decreased in pigs fed corn screenings, with an additional sharp decrease prior to onset of clinical signs. Increases in serum liver enzymes, total bilirubin, and cholesterol were present, but electrocardiograms, heart rate, and body temperature were unaffected. Pigs dosed IV with FB₁, developed mild intermittent respiratory abnormalities, while those fed screenings developed respiratory distress within 5 days. Mild interstitial pulmonary edema was observed in pig 1. Severe interstitial pulmonary edema, pleural effusion, and increased lung wet/dry weight ratio were observed in pigs 4 and 5. All pigs given fumonisin (either IV or orally) had hepatic changes characterized by hepatocyte disorganization and necrosis; pancreatic acinar cell degeneration was also observed. Ultrastructural changes in orally dosed swine included loss of sinusoidal hepatocyte microvilli; membranous material in hepatic sinusoids; and multilamellar bodies in hepatocytes, Kupffer cells, pancreatic acinar cells and pulmonary macrophages. Pulmonary intravascular macrophages (PIMs) contained large amounts of membranous material. Thus, the target organs of fumonisin in the pig are the lung, liver, and pancreas. At lower doses, slowly progressive hepatic disease is the most prominent feature, while at higher doses, acute pulmonary edema is superimposed on hepatic injury and may cause death. We hypothesize that altered sphingolipid metabolism causes hepatocellular damage resulting in release of membranous material into the circulation. This material is phagocytosed by the PIMs thus triggering the release of mediators which ultimately results in pulmonary edema.Presented in part at the 1991 Annual Meeting of the Society of Toxicology. The Toxicologist 11: 143 (A499).     

胆红素脑病SD乳鼠模型中脑水通道蛋白-4表达发生变化

神经细胞水肿是胆红素脑病（bilirubin encephalopathy,BE）发生发展过程中的重要病理变化。水通道蛋白-4（aquaporin-4,AQP4）的表达及分布异常与多种疾病所致细胞毒性脑水肿的发生发展具有密切联系。但胆红素脑病中AQP4的表达变化规律及其在病理进展中的作用尚不清楚。采用7日龄SD大鼠小脑延髓池注射胆红素溶液的方法,建立新生大鼠胆红素脑病模型。胆红素脑病模型根据胆红素作用时间的不同,分为12 h、24 h、48 h、72 h和7 d组。采用HE及尼氏染色,检测各新生大鼠脑组织的病理改变;应用透射电镜(TEM),检测胆红素作用24 h后,鼠脑组织超微结构的变化;应用免疫荧光及Western 印迹,检测 AQP4在脑组织中的表达变化。通过上述实验,以探讨AQP4的表达变化与胆红素所致脑损伤的关系。HE及尼氏染色结果显示,随着胆红素沉积时间的延长,神经细胞逐渐肿胀,细胞间隙增大,尼氏小体数量逐渐减少;电镜结果显示,胆红素脑病24 h后神经细胞线粒体出现肿胀;免疫荧光染色显示,24 h组AQP4的表达范围明显增加,其后表达范围逐渐减少,表达强度也随之减弱;Western 印迹结果显示,AQP4表达在不同时间点呈现先增高后降低的趋势,在24 h达到峰值（24 h组1.38 ± 0.11 vs 对照组0.87 ± 0.21, P＜0.05）,在之后的各时间点上,AQP4的表达呈现下降趋势,而72 h组与7 d组AQP4表达均低于48 h组（P＜0.05）,基本恢复到对照组的表达水平（P＞0.05）。上述结果提示,胆红素脑病中胆红素的毒性作用将引起AQP4表达量的改变,AQP4的表达变化与胆红素脑病中细胞毒性脑水肿的发生相关,并且可能在胆红素脑病脑损伤的进展中发挥作用。     

Brain Amino Acids During Hyponatremia In Vivo: Clinical Observations and Experimental Studies

Hyponatremia is a highly morbid condition, present in a wide range of human pathologies, that exposes patients to encephalopathic complication and the risk of permanent brain damage and death. Treating hyponatremia has proved to be difficult and still awaits safe management, avoiding the morbid sequelae of demyelinizing and necrotic lesions associated with the use of hypertonic solutions. During acute and chronic hyponatremia in vivo, the brain extrudes the excessive water by decreasing its content of electrolytes and organic osmolytes. At the cellular level, a similar response occurs upon cell swelling. Among the organic osmolytes involved in both responses, free amino acids play a prominent role because of the large intracellular pools often found in nerve cells. An overview of the changes in brain amino acid content during hyponatremia in vivo is presented and the contribution of these changes to the adaptive cell responses involved in volume regulation discussed. Additionally, new data are provided concerning changes in amino acid levels in different regions of the central nervous system after chronic hyponatremia. Results favor the role of taurine, glutamine, glutamate, and aspartate as the main amino acid osmolytes involved in the brain adaptive response to hyponatremia in vivo. Deeper knowledge of the adaptive overall and cellular brain mechanisms activated during hyponatremia would lead to the design of safer therapies for the hyponatremic patient.     

高频喷射通气治疗海水淹溺肺水肿兔肺AKP活性变化的图像定量分析

用海水灌注的方法诱发海水淹溺肺水肿（ＰＥＳＷＤ）,采取高频喷射通气（ＨＦＪＶ）治疗之。以细胞化学反应和图像定量分析为手段从碱性磷酸酶（ＡＫＰ）角度研究其病理生理变化机理。结果表明,海水灌注后ＡＫＰ产物数量和密度显著增加,ＨＦＪＶ治疗后均回落至接近正常水平。推测ＰＥＳＷＤ引起ＡＫＰ活性代偿性升高,ＨＦＪＶ后,肺部氧供应改善可能是导致ＡＫＰ活性下降的原因     

磷脂酶A2在内毒素致大鼠肺损伤中的作用

大鼠静脉注射大肠杆茵内毒素（３０ｍｇ／ｋｇ）后３ｈ肺血管外水量和支气管肺泡灌洗液中蛋白浓度明显增加,表明发生了通透性肺水肿;同时血清和支气管肺泡灌洗液中磷脂酶Ａ２（ＰＬＡ２）活性升高,且ＰＬＡ,活性的升高与肺血管外水量的增加呈显著正相关。预先给予ＰＬＡ２抑制剂对溴苯酰基溴可抑制内毒素引起的ＰＬＡ２活性升高和通透性肺水肿。提示ＰＬＡ２介导了内毒素引起的肺损伤。     

Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning

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Aminergic Neurotransmitter and Water Content Changes in Rats After Transient Forebrain Ischemia

We have studied changes of cerebral monoamine metabolism and water content, during recirculation following global transient ischemia (20 min) using the four-vessel occlusion model in rats. Levels of monoamines and their metabolites were determined in cortex, striatum, hippocampus, and hypothalamus. Water content was evaluated by weight and by the analysis of T1 and T2 relaxation times in 1H-nuclear magnetic resonance. Norepinephine levels decreased; 3,4-dihydroxyphenylethylamine, 3,4-dihydroxyphenylacetic acid, and 5-hydroxytryptamine levels oscillated and levels of the end products homovanillic acid and 5-hydroxyindole-3-acetic acid increased. The regional changes were qualitatively similar but quantitatively different, and were greatest in the hippocampus, illustrating the concept of neuronal selective vulnerability. The changes suggest an initial monoamine depletion and catabolism due to massive release from stores followed by autoregulatory processes. The water content increased moderately, with a maximum at 1 h. The variations of T1 were similar, positively correlated with water content and more pronounced in the cortex than in the white matter. T2 was markedly altered over the entire 24-h period. Those latter parameters are positively correlated with 5-hydroxytryptamine concentration in the hypothalamus consistent with a relationship between 5-hydroxytryptamine and cerebral edema.