Effect of arachidonic acid on cultured cerebromicrovascular endothelium: permeability,lipid peroxidation and membrane “fluidity”

Summary The relationship of free arachidonic acid (AA) to cellular permeability, lipid peroxidation and physical state fluidity of the membrane was investigated in cultured endothelial cells (EC) dissociated from cerebral microvessels of rats. The results demonstrate that AA can induce a reversible alteration of endothelial permeability to trypan blue albumin (TBA). Exposure of EC to AA increases membrane fluidity as measured by fluorescence anisotropy using 1,6-diphenyl-1,3,5 hexatriene as a fluorescent probe. The AA modification of EC membrane fluidity is not associated with changes in EC permeability. Addition of AA and H₂O₂ to the incubation medium of EC leads to persistant alteration of EC permeability which can be prevented by catalase treatment. Both AA and H₂O₂ induce a greater formation of malondialdehyde, the product of lipid peroxidation, than AA alone. These findings strongly suggest that a release of AA either from the capillary or cellular membrane of the brain under a pathological condition may alone or through a peroxidative process alter the function of blood-brain barrier.     

Hyperthermic effect of prostacyclin injected into the third cerebral ventricle of the cat

CLARK, W. G. AND. J. M. LIPTON. Hyperthermic effect of prostacyclin injected into the third cerebral ventricle of thecat. BRAIN RES. BULL. 4(1) 15–16, 1979.—Prostaglandin E₂ may not be solely responsible for hyperthermia produced by central administration of sodium arachidonate. To determine its effect, if any, on body temperature prostacyclin sodium salt, another product of prostaglandin endoperoxides, was injected into the third cerebral ventricle of unrestrained, unanesthetized cats while deep body temperature was recorded automatically. Doses of 2–25 μg, in a volume of 0.05 ml saline solution, did not appreciably alter body temperature. A 100 μg dose produced hyperthermia in five of six animals. Administration of 1 mg prostacyclin caused prolonged hyperthermic responses in four cats with a maximum increase in temperature of at least 2.1°C. Prostaglandin E, (1 μg) produced hyperthermic responses which were intermediate between responses to 100 and 1000 μg prostacyclin. Indomethacin (2 mg/kg), given IV to two cats during recovery from prostacyclin-induced hyperthermia, did not hasten the rate of recovery. These results indicate that, if a sufficient concentration of prostacyclin is achieved at a central site of action after injection of arachidonate or during pathologic processes which release arachidonic acid, prostacyclin could contribute to the development of hyperthermia.     

Permeability and vasomotor response of cerebral vessels during exposure to arachidonic acid

Summary Release of arachidonic acid (AA) in brain tissue is found in various cerebral insults. Blood-brain barrier function and vasomotor response were studied during cerebral administration of the fatty acid to obtain further evidence on its role as mediator of secondary brain damage under pathological conditions. Na⁺-fluorescein or fluorescein isothiocyanate (FITC)-dextran were i.v. administered as low- and high-molecular weight blood-brain barrier indicators. Cortical superfusion of arachidonic acid led to moderate constriction of ca. 90% of normal of pial arteries of 60–220 m Ø, whereas the venous diameters remained unaffected. On the other hand, AA caused opening of the blood-brain barrier not only for Na⁺-fluorescein but also for FITC-dextran (mol.wt. 62,000). Extravasation of Na⁺-fluorescein started at AA concentrations of 3×10^–5 M. Concentrations of 3×10^–4 to 3×10^–3 M always sufficed to induce barrier opening for fluorescein, whereas 3×10^–3 M was required for FITC-dextran. Leakage of the blood-brain barrier indicators started around venules. Pretreatment with indomethacin, or with BW 755 C, a dual inhibitor of both the cyclo- and lipoxygenase pathway did not prevent barrier opening by arachidonate for Na⁺-fluorescein. However, in the presence of indomethacin higher concentrations of AA were required to open the barrier for Na⁺-fluorescein, whereas BW 755 C did not influence the dose-effect relationship of AA and barrier opening observed in untreated animals. The latter findings imply that the pathophysiological effects induced by AA are likely to be attributed to the acid itself, rather than to its metabolites, a conclusion which might be in conflict with earlier observations reported in the literature. Electron microscopy revealed marked alterations of the venous endothelium, such as an attachment and eventual penetration of polymorphonuclear granulocytes through the endothelial barrier, while the small arteries and arterioles were unaffected. The findings may indicate that opening of the barrier by AA is mediated by granulocytes and/or their products. Taken together, our findings support the concept that release of AA in primarily damaged brain tissue enhances secondary processes, such as a failure of the blood-brain barrier function. The limited potency or even ineffectiveness, respectively, of indomethacin or BW 755 C provides evidence for a direct involvement of the fatty acid rather than of its metabolic degradation products. Therefore, therapeutic prevention of AA formation under these circumstances might be superior to mere inhibition of its metabolism.Supported by the Deutsche Forschungsgemeinschaft Ba 452/6-5 and Wa 441/2-3     

Neuropathology of citrullinaemia

Summary A peculiar ultrastructural change of the cytoplasmic membrane is described. It concerns selective destruction of the outer leaflet of the luminal side of the capillary endothelium in the white matter of the rat brain. 30 min and 3h after intracerebral injection of arachidonic acid (AA). The cristae of the mitochondria disappeared in the endothelium of many capillaries. These changes were observed mainly in the central part of brain edema, where the extracellular space was markedly widened.The possible mechanism whereby these changes developed is discussed.     

Vascular lipoxygenase activity: synthesis of 15-hydroxyeicosatetraenoic acid from arachidonic acid by blood vessels and cultured vascular endothelial cells

Although indirect pharmacologic evidence has suggested the presence of a lipoxygenase pathway of arachidonic acid (AA) metabolism in blood vessels, direct biochemical evidence has been difficult to demonstrate. We have investigated lipoxygenase metabolism in both fresh vessel preparations and cultured vascular cells from various sources and species. Lipoxygenase-derived [³H]HETE (composed of 12-HETE, 15-HETE and 5-HETE), which was abolished by ETYA but not by aspirin, was formed when [³H]AA was incubated with fresh sections of rat aorta. Lipoxygenase activity was lost following deendothelialization. A single peak of [³H]15-HETE was produced by cultured bovine aortic and human umbilical vein endothelial cells (EC) in response to exogenous [³H]AA or from [³H]AA released by ionophore A23187 from endogenous EC membrane phospholipid pools. Cultured bovine, rabbit or rat aorta smooth muscle cells had no detectable 15-lipoxygenase activity. ¹⁴C]Linoleic acid was converted by EC to its 15-lipoxygenase metabolite, [¹⁴C]13-hydroxyoctadecadienoic acid. These results indicate that blood vessels from different sources and species have a 15-lipoxygenase system, and this activity resides predominantly in the endothelial cells.     

Uptake of leucine and alanine by cultured cerebral capillary endothelial cells

Pure cultures of rat cerebral capillary endothelium have been used to study the A- and L-systems of amino acid transport. Leucine is taken up by a non-concentrative mechanism that can be saturated, and competivively inhibited by phenylalanine. Uptake is rapid, with equilibiration apparent 3–min (al experiments performed at 37 °C). The K_M for transport was 83 μM ± 26(mean ±S.E.M.., n = 3 which is in good agreement with recent vi vivo report using unanesthtissed rats. Alanine was transported by a saturable, concentrative mechanism. Dependence on Na⁺ -ions was demonstrated by lack of specific uptake in Na⁺ -ffree buffer and reduced uptake after preincubation in ouabain — Na⁺, K⁺ -ATPase inhibitor. The K_M was 325 μM ±88 (mean ± S.E.M., n = 3). The finding ac an active A-system transporter in vitro suggests that the cells may have lost the polarity they demonstrate in vivo. The relevance of these findings to transport of nutrients nd drugs across the blood-brain barrier is discussed.     

Glycerophosphoinositol and dexamethasone improve transendothelial electrical resistance in an in vitro study of the blood-brain barrier

The blood-brain barrier (BBB) maintains the homeostasis of the brain microenvironment, which is crucial for neuronal activity and function. Under pathological conditions, the BBB may fail due to yet unknown mechanisms. BBB failure is accompanied by an increase in the transendothelial permeability to substances such as sucrose that are normally extruded. Furthermore, altered BBB function may also lead to development of abnormal drug extrusion mechanisms including expression of multiple drug resistance proteins. Therefore, it is not surprising that strategies have been developed to "repair" the BBB in order to restore normal brain homeostasis and penetration/extrusion of pharmacologically active (noxious) substances. To this end, steroidal hormones and synthetic analogues such as dexamethasone (DEX) have been used to counteract BBB failure. However, several side effects limit the usefulness of steroid treatment in humans leading to the quest for developing novel strategies for BBB repair. We here show that, in an in vitro model of the BBB based on a co-culture of endothelial cells (EC) and glia, the natural compound glycerophosphoinositol (GPI) may replicate the effects of DEX. Thus, GPI in concentrations ranging from 3 to 100 microM promoted both BBB formation and repair in a dose dependent fashion. Similar effects were obtained with an elevated dose of DEX (10 microM); at higher concentrations (100 microM), DEX was cytotoxic. We conclude that the endogenous anti-inflammatory agent GPI may ameliorate BBB function with efficacy comparable to that of steroids, but with significantly fewer side effects. Further experiments will confirm the efficacy of this treatment in vivo and elucidate the pathways that lead to BBB repair after exposure to GPI.     

The effect of dexamethasone on vascular permeability of experimental brain tumours

Summary The vessels of experimental gliomas show an abnormally high permeability to small polar molecules, such as mannitol. To establish whether this change in vessel permeability is modified by treatment with the corticosteroid dexamethasone, the kinetics of [¹⁴C]mannitol transfer into rat astrocytomas were estimated in both steroid- and saline-treated, tumourbearing animals. This was achieved by injecting [¹⁴C]mannitol i.v., using a specially devised technique, so as to maintain a constant concentration of tracer in the blood plasma. In separate experiments steady levels of the tracer were maintained in the circulation from 1 to 30 min. Mean plasma and tumour radioactivity were measured, and the apparent transfer constant of mannitol across the vascular endothelium and the size of the extravascular extracellular mannitol space in the tumours were calculated.Despite a significant clinical improvement in the treated animals and adequate circulating levels of dexamethasone at the time of the permeability studies, no difference in either the apparent transfer constant for the movement of mannitol into the tumours or the fractional extracellular mannitol space was detected between these animals and the controls. With steroid treatment both tumour-bearing and non-tumour bearing animals lost weight, and in the latter there was no consistent change in routine biochemical or haematological parameters. It was concluded that under these conditions it is unlikely that clinical improvement with dexamethasone therapy was due to a non-specific reduction in tumour vessel permeability to polar substances.A preliminary account of this work was presented at the Sixty-Eighth Meeting of the British Neuropathological Society, January 1985Supported by the Wellcome Trust and the Medical Research Council     

Functional deterioration of endothelial nitric oxide synthase after focal cerebral ischemia

Endothelial nitric oxide synthase (eNOS) dysfunction is related to secondary injury and lesion expansion after cerebral ischemia. To date, there are few reports about postischemic alterations in the eNOS regulatory system. The purpose of the present study was to clarify eNOS expression, Ser1177 phosphorylation, and monomer formation after cerebral ischemia. Male Wistar rats were subjected to transient focal cerebral ischemia. Endothelial nitric oxide synthase messenger RNA (mRNA) and protein expression increased ∼8-fold in the ischemic lesion. In the middle cerebral artery core, eNOS-Ser1177 phosphorylation increased 6 hours after ischemia; however, there was an approximately 90% decrease in eNOS-Ser1177 phosphorylation observed 24 hours after ischemia that continued until at least 7 days after ischemia. Endothelial nitric oxide synthase monomer formation also increased 24 and 48 hours after ischemia (P<0.05), and protein nitration progressed in parallel with monomerization. To assess the effect of a neuroprotective agent on eNOS dysfunction, we evaluated the effect of fasudil, a Rho-kinase inhibitor, on eNOS phosphorylation and dimerization. Postischemic treatment with fasudil suppressed lesion expansion and dephosphorylation and monomer formation of eNOS. In conclusion, functional deterioration of eNOS progressed after cerebral ischemia. Rho-kinase inhibitors can reduce ischemic lesion expansion as well as eNOS dysfunction in the ischemic brain.     

Cerebral endothelial regeneration following experimental brain injury

Summary It is still unknown when and in which area endothelial regeneration occurs after brain injury, and to what extent such changes depend on the severity of the injury. We have, therefore, studied bromodeoxyuridine (BrdU) uptake by regenerating endothelial cells in two different groups of rats given cold lesions using immunohistochemistry employing anti-BrdU monoclonal antibody, anti-factor VIII-related antigen antibody and anti-glial fibrillary acidic protein antibody. The earliest evidence for the presence of BrdU-positive endothelial cells (BrdU+end) was observed at 2 days after injury, the injured endothelial cells regenerating from the edge toward the center of the lesion in both groups. We considered that edema fluid could act as an important factor, since at 2 days post-injury BrdU+end were not in contact with macrophages and were always found in Evans blue-stained areas. Study of endothelial cell kinetics also confirmed that the repair of injured endothelial cells was intimately involved in the reconstruction of the blood-brain barrier, since the time of disappearance of BrdU+end coincided with the disappearance of Evans blue-stained areas. The difference in the process of endothelial regeneration was first apparent on the 3rd day, there being no difference at 2 days.     

Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide-mediated regulation of vascular endothelial growth factor and metalloproteinases

Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of β-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.     

Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus

We investigated the effect of arachidonic acid (AA) on the release of [3H]acetylcholine ([3H]ACh) from the rat hippocampus. AA (3-30 microM) increased the basal tritium outflow and the field-electrically evoked release of [3H]ACh from hippocampal slices in a concentration-dependent manner. AA (30 microM) produced a 69+/-7% facilitation of the evoked and a 36+/-3% facilitation of basal tritium outflow. The effect of AA (30 microM) on the evoked tritium release was prevented by bovine serum albumin (BSA, 1%), which quenches AA, and was unaffected by the cyclooxygenase inhibitor, indomethacin (100 microM), and the lipooxygenase inhibitor, nordihydroguaiaretic acid (50 microM). Phospholipase A2 (PLA2, 2 U/ml), an enzyme that releases AA from the sn-2 position of phospholipids, mimicked the facilitatory effect of AA on the evoked tritium release (86+/-14% facilitation), an effect prevented by BSA (1%). The PLA2 activator, melittin (1 microM), enhanced the evoked tritium release by 98+/-11%, an effect prevented by the PLA2 inhibitor, arachidonyl trifluromethylketone (AACOCF3, 20 microM), and by BSA (1%). AA (30 microM), but not arachidic acid (30 microM), also facilitated (72+/-9%) the veratridine (10 microM)-evoked [3H]ACh release from superfused hippocampal synaptosomes, whereas PLA2 (2 U/ml) and melittin (1 microM) caused a lower facilitation (46+/-1% and 38+/-5%, respectively). The present results show that both exogenously added and endogenously produced AA increase the evoked release of [3H]ACh from rat hippocampal nerve terminals. Since muscarinic activation triggers AA production and we now observed that AA enhances ACh release, it is proposed that AA may act as a facilitatory retrograde messenger in hippocampal cholinergic muscarinic transmission as it has been proposed to act in glutamatergic transmission.     

Arachidonsäure-metabolismus nach aneurysmaruptur

Zusammenfassung Der gestbrten Homöostase zwischen den Arachidonsauremetaboliten Prostacylin (PGI₂) and Thromboxan A₂ (TXA₂) kommt nach experimentellen Untersuchungen eine wesentliche Bedeutung fur die Entstehung cerebraler Vasospasmen nach Subarachnoidalblutung zu. Um die klinische Relevanz dieser Hypothese zu überprüfen wurden bei 12 Patienten nach Aneurysmaruptur die prä- und postoperativen Serum- and Liquorspiegel von PGI₂ and TXA₂ untersucht. Die Konzentrationen beider Substanzen wurden als Funktion ihrer stabilen Abbauprodukte 6-Keto-PGF₁(PGI₂) und Thromboxan B₂ (TXA₂) mittels eines hochspezifischen Radioimmunoassays bestimmt. Die Serumspiegel beider Metaboliten waren bei der Hälfte der Patienten prä- und postoperativ deutlich erhöht, zeigten aber insgesamt einen unspezifischen Verlauf ohne erkennbare Beziehung zum klinischen Krankheitsablauf. Demgegenuber fand sich eine eindeutige Korrelation zwischen der Höhe der initialen Liquorkonzentration von TXB₂ and dent Ausmaß der comutertomographisch nachweisbaren Subarachnoidalblutung. Einem sekundaren postoperativen Thromboxan B₂ Anstieg im Liquor kommt dariiberhinaus offensichtlich eine Bedeutung in der Entwicklung cerebraler Gefaf3spasmen mit nachfolgender klinischer Verschlechterung zu. Die 6-Keto-PGF₁-Spiegel waren prä- und postoperativ nur leicht bis mäßig erhöht und wurden von den gesteigerten TXB₂-Konzentrationen signifikant übertroffen. Es wird geschlossen, daß dem prä- und post-operativen Monitoring von Arachidonsäuremetaboliten eine mögliche Bedeutung in der Überwachung von Patienten nach Subarachnoidalblutung zukommt, insbesondere im Hinblick auf eine frühzeitige Erkennung insipienter cerebraler Vasospasmen.

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Arachidonic acid metabolism following aneurysm rupture

Summary Imbalance between the two arachidonic acid metabolites, prostacyclin (PGI₂) and thromboxane A₂ (TXA₂), is thought to be at least in part responsible for the development of cerebral vasospasm following aneurysm rupture. In 12 patients with subarachnoid hemorrhage the pre- and postoperative serum and CSF levels of PGI₂ and TXA₂ were measured as a function of their stable hydrolysis products, 6-Keto-PGF₁ (PGI₂) and thromboxane B₂ (TXA₂), with a highly specific radioimmunoassay. Serum levels of both metabolites were elevated in half of the patients, but no correlation to the clinical course could be found. However, TXB₂ concentration in the CSF was significantly increased preoperatively with close correlation to the amount of intracisternal blood, as detected by CT scan. Furthermore, it could be demonstrated that the post-operative course of the TXB₂ concentrations in the CSF reflects the clinical course in such a way that a characterstic secondary rise of TXB₂, concentration postoperatively is closely related to the occurrence of cerebral vasospasm and clinical deterioration. The conclusion is drawn that measurement of arachidonic acid metabolites in the CSF may provide important information concerning the pathophysiological events following subarachnoid hemorrhage, especially with regard to incipient cerebral vasospasm.

     

Ahmed青光眼阀植入后角膜内皮细胞的变化

背景：青光眼阀通常植入到眼球颞上方位置,由于角膜内皮细胞不能再生,颞上方内皮细胞的创伤修复主要靠其他区域健康内皮细胞的扩展和延伸来补偿,因此会出现内皮细胞密度的下降和形态改变。目的：观察Ahmed青光眼阀植入前后角膜内皮细胞密度及形态学的变化规律。方法：在34例(34眼)疑难青光眼患者眼球颞上象限行Ahmed青光眼阀植入,移植前及移植后3,6个月对角膜中央、颞上、颞下、鼻上及鼻下区内皮摄像后测定分析,得出角膜内皮细胞密度,并取全角膜平均值,同时观察角膜内皮细胞形态变化,统计六角形细胞所占比例。结果与结论：Ahmed青光眼阀植入后全角膜内皮细胞的平均密度有所下降,并在一段时间内呈渐进性趋势(P < 0.05),其中角膜颞上区较中央区下降明显,角膜中央区内皮细胞密度移植前后无明显变化。移植后角膜内皮细胞在形态学方面也发生了变化,六角形细胞比例下降,多边形细胞比例增加(P < 0.05)。结果显示,Ahmed青光眼阀植入后6个月内角膜内皮细胞密度呈渐近性下降趁势,形态学特征亦有所改变。提示植入过程中应注意眼内操作的轻柔性,从而降低对角膜内皮细胞的损害,并延长对移植后患者角膜内皮的监测时间。 关键词：青光眼阀;角膜内皮;角膜内皮计;细胞密度;细胞形态doi:10.3969/j.issn.1673-8225.2010.03.027     

Heparan sulfate as a venostatic endothelial stabilizing factor

A humoral transfer of a factor inducing a decrease of circulating endothelial cells (CEC) released during venostasis was demonstrated in rats. The possibility to block its activity by an in-vitro addition of protamine suggests its identity with an endogenous heparan sulfate possessing an inhibitory effect on endothelial turnover. This was supported by an analogous effect of intravenously administered heparan sulfate-related agent.     

Platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by human brain microvessel endothelial cells in primary culture

PECAM-1 expression was investigated in primary cultures of human brain microvessel endothelial cells (HBMEC). HBMEC constitutively express PECAM-1 along their apical cell surface, advancing processes and on the basal surface at points of contact with the extracellular matrix. Surface expression is not altered by cytokine or lipopolysaccharide treatment. This distribution may mediate cell-cell contact and migration during angiogenesis and HBMEC-leukocyte interactions in CNS inflammation.     

The culture of vascular endothelial cells to confluence on microporous membranes

We have designed a two compartment system in which upper and lower compartments are separated by a layer of vascular endothelial cells grown on a porous membrane. The culture of pig aortic endothelial cells and their growth to confluence on porous PTFE membranes is described and the principal characteristics of membrane-cultured endothelium are compared with those of similar cells cultured on solid surfaces. While growth of endothelium to visual confluence was slower on the PTFE membranes than on solid surfaces, gross morphology and ratio of 6 keto prostaglandin F₁ to prostaglandin E₂ production by the cells was similar. A decrease in fluid flow across the membrane-cultured cells was associated with their growth to visual confluence: from low levels, fluid flow could be increased markedly by altering the environmental temperature of the cells. The possible uses and limitations of such a system in the interpretation of the role of endothelial cells in selective transport and compartmentation of fluid and cellular components of the blood are discussed.     

Thromboxane A2 and the endoperoxides mediate canine platelet activation

With canine platelets, arachidonate consistently induces a shape change and potentiates the response to a submaximal ADP stimulus even though it does not generally induce aggregation. We have determined that TXA₂ and possibly the endoperoxides are responsible for these effects based on the following data: (i) indomethacin (14uM) blocks both actions of arachidonate, (ii) imidazole (5uM) partially blocks both, and (iii) the endoperoxide analog, U-46619, produces effects similar to arachidonate, whereas other stable metabolites of arachidonate (PGE₂, PGF₂, PGD₂, PGI₂, 6-keto-PGF₁ and TXB₂) do not. Specifically, PGI₂ and PGD₂ inhibit ADP-induced aggregation; low concentrations of PGE₂ and PGF₂ facilitate secondary aggregation; and the other metabolites are relatively inactive. With the exception of PGF₂ , these activities are qualitiatively identical to those observed with human platelets. A decreased sensitivity of canine platelets to TXA₂ and the endoperoxides is advanced as the explanation of their diminished responsiveness to arachidonate relative to other species.     

环氧二十碳三烯酸在脑出血中的作用研究进展

环氧二十碳三烯酸(EETs)主要由细胞内花生四烯酸在细胞色素P450环氧化酶催化下产生,并可由可溶性环氧化物水解酶降解为活性较低的二羟基二十碳四烯酸。近年来研究发现,EETs在神经组织中具有抗炎症反应、抗动脉粥样硬化、抗细胞凋亡和促进血管生成等作用,已成为多种神经系统疾病防治的新靶点。脑出血是一种严重的急性脑血管疾病,继发性脑损伤是其重要损伤机制之一。目前研究证实EETs对脑出血后的脑组织具有保护作用,因此成为了脑出血防治研究的新热点。笔者现围绕EETs在脑出血中的作用及其机制的研究进展展开综述,以期为脑出血治疗中新的研究方向及治疗靶点的探索提供一定参考。