过氧化物酶体增殖物激活受体γ在大鼠脊髓损伤后继发性损伤中的表达变化

目的 观察大鼠脊髓损伤后继发性损伤中过氧化物酶体增殖物激活受体γ(PPARγ)表达的变化.方法 将72只雄性SD大鼠按照随机数字表法分为损伤组(建立大鼠脊髓损伤模型)和对照组(仅显露脊髓,不做打击伤),每组各36只.实时免疫荧光定量多聚酶链反应(FQ-PCR)检测脊髓损伤后1 d、3 d、7 d、14 d、28 d、56 dPPARγmRNA的表达变化,每个时间点取6只大鼠.蛋白印记检测脊髓损伤后1 d、3 d、7 d、14 d、28 d、56 d PPARγ的表达变化.结果 与对照组比较,损伤组脊髓组织中PPARγmRNA和PPARγ表达均明显增加,差异均有统计学意义(P＜0.05),其表达高峰在脊髓损伤后14d.结论 脊髓损伤后在继发性损伤中PPARγ的表达明显增加,表达高峰在脊髓损伤后14d.     

过氧化物酶体增殖物激活受体γ在阿尔茨海默病中的研究进展

AD是-种以老年斑、神经纤维缠结、突触密度减少和神经元丢失为主要病理改变的神经退行性疾病.过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARy)是配体激活核转录因子,具有调节能量代谢和糖脂代谢,参与胰岛素的敏感性调节以及脂肪细胞和巨噬细胞分化,抑制炎性基因表达等生物学作用.     

过氧化物酶体增殖物激活受体γ在垂体腺瘤中的表达

目的 通过检测过氧化物酶体增殖物激活受体γ(PPARγ)在人垂体腺瘤组织中的表达,探讨其在垂体腺瘤中的相关机制.方法 通过免疫组化法确定经手术切除的83例垂体腺瘤组织细胞来源;采用RT-PCR、适时定量PCR检测研究83例垂体腺瘤组织及6例正常垂体组织PPARγ的mRNA表达量,采用Western blot法检测组织PPARγ蛋白质表达水平,分析不同类型垂体腺瘤组织之间核酸及蛋白水平表达量的差异.结果 GH腺瘤17例、PRL腺瘤15例、ACTH腺瘤18例、多激素腺瘤(MCPAs)17例、无功能腺瘤(NFAs)16例及正常对照组6例;mRNA水平检测显示所有垂体腺瘤组织的表达量均高于正常对照组,其中GH腺瘤的表达量最高,与其他组比较P＜0.05;蛋白水平检测显示GH腺瘤、PRL腺瘤、ACTH腺瘤及MCPAs的表达量均高于正常对照组(P＜0.05),GH腺瘤的表达量最高,NFAs的表达量与正常对照组差异无统计学意义(P＞0.05).结论 PPARγ转录及蛋白表达水平在人GH、PRL、ACTH及MCPAs垂体腺瘤组织中高表达,该基因与垂体腺瘤有一定的相关性,而无功能垂体腺瘤在核酸水平的表达量增高,蛋白水平的表达量不高,可能与激素的分泌水平有关;在GH腺瘤中的表达量最高,且与其他组相比,差异有统计学意义(P＜0.05),说明该类肿瘤与PPARγ的关系最为密切,可能与生长激素能刺激PPARγ的表达有关.     

原代培养人单核细胞中过氧化物酶体增殖物激活受体γ表达与阿托伐他汀的干预

背景：阿托伐他汀作为过氧化酶体增殖体激活受体γ的激动剂,不仅可以调节脂质代谢,而且能够抑制炎症递质生产,减轻缺血性炎症损伤,但其具体作用机制尚不明确。 目的：观察原代培养的人单核细胞中阿托伐他汀对过氧化物酶增殖体激活受体的影响和抗炎作用。 方法：将原代培养的人单核细胞随机分为对照组,10,1,0.1 µmol/L阿托伐他汀组和抗过氧化酶体增殖体激活受体γ抗体组;预先被肿瘤坏死因子α激活的人单核细胞随机分为对照组,0.1,1,10 µmol/L阿托伐他汀组,分别和不同浓度的阿托伐他汀共同孵育24 h,通过电泳迁移率变化分析抗过氧化酶体增殖体激活受体γ蛋白的表达情况,通过酶联免疫吸附实验测定肿瘤坏死因子α、单核细胞趋化蛋白1、明胶酶B的水平,并且通过氧电极法测定细胞氧耗量。 结果与结论：在未被肿瘤坏死因子α激活的单核细胞中,阿托伐他汀可以呈浓度依赖性激活抗过氧化酶体增殖体激活受体γ,降低单核细胞趋化蛋白1、降低明胶酶B的水平,但对肿瘤坏死因子α的水平没有明显影响。而在预先被肿瘤坏死因子α激活的单核细胞中,阿托伐他汀使抗过氧化酶体增殖体激活受体γ上调的作用并不明显,但仍可浓度依赖性降低肿瘤坏死因子α、单核细胞趋化蛋白1 和明胶酶B的水平,同时阿托伐他汀呈浓度依赖性降低细胞氧耗量达41%。说明阿托伐他汀具有确切的抗炎效果,但这种作用并不完全依赖于过氧化物酶体增殖体激活受体γ途径。     

羟基红花黄色素A对谷氨酸诱导损伤神经元过氧化物酶体增殖物激活受体γ表达的影响

目的探讨羟基红花黄色素A(HSYA)拮抗谷氨酸诱导神经元损伤的保护机制。方法采集经体外原代培养第7天的Sprague Dawley胎鼠皮质神经元,通过形态学观察、噻唑蓝法、Westernblotting法分别检测过氧化物酶体增殖物激活受体γ(PPARγ)和磷酸化PPARγ(pPPARγ,即PPARγ的失活形式)表达水平,以探讨HSYA抗谷氨酸诱导神经元损伤的保护机制。结果经谷氨酸处理后神经元发生肿胀、部分崩解、死亡。与正常对照组相比,谷氨酸不同剂量组(1.00、5.00和10.00mmol/L组)的神经元存活率(66.60%、33.40%和21.60%)和PPARγ蛋白表达水平显著降低,对照组灰度值:1.06±0.18,谷氨酸5.00和10.00mmol/L组灰度值分别为:0.32±0.09、0.28±0.07(均P=0.000),pPPARγ蛋白表达水平明显升高,灰度值分别为:0.37±0.05、1.83±0.17和1.75±0.21(均P=0.000)。HSYA与谷氨酸共同处理后神经元形态明显改善、细胞相对存活率提高,谷氨酸5.00mmol/L,HSYA0.01、0.10和1.00mmol/L组分别为33.40%、35.30%、51.00%和72.50%(P=0.742、0.033、0.002),PPARγ蛋白表达水平呈现逐渐升高趋势,对照组,谷氨酸5.00mmol/L,HSYA0.01、0.10和1.00mmol/L组灰度值分别为:1.20±0.16、0.25±0.06、0.39±0.10、0.41±0.12、0.37±0.08,但差异未达到统计学意义(均P>0.05),pPPARγ蛋白表达水平降低,对照组,谷氨酸5.00mmol/L,HSYA0.01、0.10和1.00mmol/L组灰度值分别为:0.51±0.14、1.91±0.25、1.70±0.26、1.25±0.23、0.85±0.19,(P=0.022、0.004、0.000)。结论 HSYA对由谷氨酸诱导的神经元损伤具有保护作用,其机制与抑制PPARγ蛋白磷酸化即抑制PPARγ活性有关。     

过氧化物酶体增殖物激活受体-γ在人侵袭性垂体腺瘤中的分布与表达

目的研究过氧化物酶体增殖物激活受体-γ(PPAR-γ)在人侵袭性垂体腺瘤组织中的分布情况和表达水平。方法30例垂体腺瘤组织依据影像学Knosp分级及术中所见分为侵袭组与非侵袭组。免疫组织化学染色分析PPAR-γ在垂体腺瘤组织中的分布情况,W estern B lot分析PPAR-γ在垂体腺瘤中的表达水平,比较PPAR-γ在侵袭性组与非侵袭组之间、各种内分泌类型腺瘤的侵袭组与非侵袭组之间分布与表达差异。结果侵袭组PPAR-γ表达水平明显高于非侵袭性组(P<0.05),侵袭性泌乳素腺瘤、侵袭性无功能腺瘤中PPAR-γ的表达水平显著高于相应的非侵袭组(P<0.05),而在生长激素腺瘤中,侵袭组与非侵袭组间PPAR-γ表达水平无明显差异(P>0.1)。结论PPAR-γ可能在人垂体腺瘤侵袭性方面发挥重要作用,并有可能成为侵袭性垂体腺瘤治疗的新靶点。     

偏头痛患者发作期血浆中过氧化物酶体增殖物激活受体β/δ水平的研究

目的观察偏头痛患者血浆中过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptorβ/δ,PPARβ/δ)水平,探究其与偏头痛的关系及临床意义。方法收集偏头痛发作期患者共59例作为病例组,再根据患者有无先兆症状分成有先兆组和无先兆组两个亚组,同时选取27例健康者作为对照组。采用酶联免疫法(ELISA)检测受试者血浆PPARβ/δ水平,采用SPSS系统软件进行统计分析。结果偏头痛患者血浆中PPARβ/δ水平明显高于健康对照者,差异有统计学意义(P<0.01);有先兆和无先兆偏头痛患者发作期血浆中PPARβ/δ水平比较无明显差异(P>0.05)。结论 PARβ/δ可能参与了偏头痛的发病过程;与有无先兆无关。     

紫外激光辐射区肝组织β连环蛋白及过氧化物酶体增殖物激活受体γ蛋白的表达*☆

背景：研究表明经典的wnt信号途径可通过抑制成脂分化关键因子过氧化物酶体增殖物激活受体γ而抑制细胞向脂肪细胞的分化。 目的：观察紫外光辐射肝组织致创后自然恢复期不同阶段β连环蛋白及过氧化物酶体增殖物激活受体γ的表达。方法：将雄性SD大鼠随机分4组：激光致创组大鼠是以355 nm紫外激光辐射肝叶形成损伤区,器械致创对照组则以手术剪肝叶致创,假手术组仅做腹部切开及缝合,正常组大鼠仅实施正常喂养。 结果与结论：紫外激光可在肝组织形成边缘整齐的消融区并在周围形成可自然修复的有限致损区域。免疫组织化学图像平面测量表明紫外激光辐射后自然恢复1周大鼠肝组织中β连环蛋白表达低于各对照组(P < 0.01),而自然恢复表达β连环蛋白 辐射区周围组织表达高于正常(P < 0.01)。蛋白印迹结果显示辐射致创组辐射后自然同时过氧化物酶体增殖物激活受体γ蛋白2周 恢复高于1周恢复(P < 0.01),且恢复期肝组织中可同时表达过氧化物酶体增殖物激活受体γ 1及2。结果证实,辐射区旁组织自然恢复各阶段存在不同的β连环蛋白及过氧化物酶体增殖物激活受体γ表达调控,2周自然恢复后辐射区旁组织成脂进程得到加强。     

过氧化物酶体增殖物激活受体γ在中枢神经系统疾病中作用的研究进展

过氧化物酶体增殖物激活受体Υ(PPARΥ)是一种配体激活的核转录医子.它参与调节脂质代谢、脂肪生成、胰岛素敏感、炎症反应、细胞生长和分化等重要生化反应及生物调节过程.本文先对PPARΥ及其配体做一简介,然后就其在脑缺血及缺血再灌注损伤、创伤性脑外伤及脊髓损伤、癫痫、运动障碍性疾病、神经变性性疾病和脱髓鞘疾病中的抗炎、抗氧化作用及其机制进行综述.     

过氧化物酶增殖体激活受体γ与进展性脑梗死相关性的探讨

目的探讨过氧化物酶增殖体激活受体γ(PPARγ)与急性进展性脑梗死的相关性。方法将45例进展性脑梗死患者为进展组,并选择与进展性脑梗死患者年龄、性别、既往疾病史相匹配的同期住院的非进展性脑梗死患者45例为非进展组,并设健康对照组45例。分离外周血有核细胞并采用RT-PCR检测PPARγ基因的表达水平。结果在入院后72 h进展组患者PPARγ水平均低于非进展组和健康对照组(P<0.01);进展组患者的PPARγ水平与低密度脂蛋白胆固醇以及高密度脂蛋白胆固醇相关(P<0.05),治疗4 w后两组患者的PPARγ在不同的神经功能恢复水平分组(mRS≤2分或mRS>2分)中表达相当。结论外周血细胞的PPARγ表达与进展性脑梗死具有相关性。     

局灶性脑缺血再灌注大鼠过氧化物酶体增殖物激活受体亚型表达的改变

目的 观察局灶性脑缺血再灌注大鼠过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)各亚型(PPARα、PPARδ/β和PPARγ)表达的改变,并初步探讨PPAR改变的意义.方法 健康雄性SD大鼠分为假手术组、模型组、治疗组.制作大鼠大脑中动脉阻塞2 h再灌注22 h模型(MCAO/R),治疗组于MCAO/R前1 h给予PPAR全激动剂苯扎贝特.分别采用3%氯化三苯四唑(2,3,5-triphenyhetrazolium,TTC)染色法观察脑梗死体积;Western blot法和免疫组织化学法观察PPAR各亚型蛋白表达和分布的变化.结果 与假手术组相比,脑缺血再灌注(1)引起梗死的平均体积为44.30%;(2)使脑组织PPAR各亚型表达均增加,分别增加了1.47、3.52和2.25倍,差别具有统计学意义(免疫组织化学检测t值分别为8.63、9.29和13.62,Western blot检测t值分别为8.16、9.24和6.43,均P=0.000);(3)PPAR各亚型免疫阳性细胞增加主要表现在缺血侧半暗带区域,而非缺血侧(对侧)表达没有明显改变.与模型组相比,苯扎贝特能够:(1)显著降低脑梗死体积,平均减少54.36%,差异具有统计学意义(t=7.69,P=0.000);(2)进一步增加PPAR各亚型表达,分别增加了95.45%、183.47%、224.61%,差异具有统计学意义(免疫组织化学检测t值分别为7.36、5.64和10.50,Western blot检测t值分别为13.02、17.52和13.64,均P=0.000);(3)不但使缺血侧PPAR免疫阳性细胞增加,而且使非缺血侧增加.结论 局灶性脑缺血再灌注损伤大鼠脑组织PPARα、PPARδ/β和PPARγ表达增加,可能是脑组织的一种代偿性神经保护反应.     

Broad-spectrum neuroprotection against traumatic brain injury by agonism of peroxisome proliferator-activated receptors

In a recent issue of Experimental Neurology, Sauerbeck and colleagues demonstrated that treatment with the peroxisome proliferator-activated receptor (PPAR) agonist Pioglitazone after experimental traumatic brain injury (TBI) in rats was protective against mitochondrial dysfunction, cognitive impairment, cortical tissue loss and microglial activation. In this commentary, we review the key findings of this work and their relevance to previous and future neurotrauma research. More broadly, we speculate about their significance in the context of developing therapeutic strategies for a wide range of neuroinflammatory conditions.     

Autoradiographic investigation of cell proliferation in the brain of spontaneously hypertensive rats

Summary Cell proliferation in the brain of spontaneously hypertensive rats (SHR) and control Wistar rats of various ages was autoradiographically investigated using [³H]thymidine. The brain of SHR showed an increase in labeled cells. The increase of labeled cells was seen in the early stage of the development of hypertension when there were still no definite morphological changes in the cerebral vessel walls or brain parenchyma. The labeled cells tended to increase in number with the age of the animals. The distribution of these cells corresponded with areas of increased vascular permeability and cerebrovascular lesions, that is, water-shed regions. The labeled cells consisted of endothelial and adventitial cells of the intracerebral arterioles and pial arteries as well as glial cells. Arachnoid cells, subarachnoid cells, medial smooth muscle cells of the pial arteries were also labeled, though less intensely. The significance of labeled endothelial cells in the development of cerebrovascular changes and sequential parenchymal changes is discussed.     

Increased expression of the mineralocorticoid receptor in the brain of spontaneously hypertensive rats

The mineralocorticoid receptor (MR) has been considered as both neuroprotective and damaging to the function of the central nervous system. MR may be also involved in central regulation of blood pressure. In the present study, we compared the expression of MR and the glucocorticoid receptor (GR) in the hippocampus and hypothalamus of 16-week-old spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats. In the hippocampus, MR expression was studied by in situ hybridization (ISH), quantitative polymerase chain reaction (PCR) and immunohistochemistry, whereas GR expression was analysed using the latter two procedures. Hypertensive animals showed an increased expression of MR mRNA in the whole hippocampus according to qPCR data and also in CA3 by ISH. Immunocytochemical staining for MR of the dorsal hippocampus, however, did not reveal differences between SHR and WKY rats. SHR showed elevated hypothalamic MR mRNA by qPCR, as well as an increased number of MR immunopositive cells in the magnocellular paraventricular region, compared to WKY rats. By contrast, expression levels of GR mRNA or protein in the hippocampus and hypothalamus of SHR were similar to those of WKY rats. Furthermore, we investigated the role of MR in the hypertensive rats by i.c.v. injection of the MR antagonist RU-2831. This compound produced a significant drop in blood pressure for SHR. In conclusion, MR expression is increased in the hippocampus and hypothalamus of SHR. We suggest that pathological MR overdrive may take responsibility for up-regulation of blood pressure and the encephalopathy of hypertension.     

Expression for peroxisome proliferator-activated receptor gamma in pituitary adenomas☆ 38 cases for semi-quantitative immunohistochemical analysis

BACKGROUND： It has been reported that peroxisome proliferator-activated receptor γ （PPAR γ ） is highly expressed in lung cancer, colon cancer, and gastric cancer, as well as other tumors.
OBJECTIVE： To study expression of PPAR γ in pituitary adenomas and analyze the role of PPAR γ in hormonal typing of pituitary adenomas.
DESIGN, TIME AND SETTING： Semi-quantitative immunohistochemistry of pathological specimens. The experiment was conducted at the Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University between January 2002 and May 2005.
MATERIALS： Surgical resection samples of pituitary adenomas from 38 cases （18 male and 20 female） were analyzed. Eight cases were determined to be invasive pituitary adenomas and 30 cases were non-invasive pituitary adenomas. Hormonal classification of the types of pituitary adenomas revealed somatotrophic adenomas in six cases, corticotrophic adenoma in five cases, prolactinomas in 13 cases, multi-hormone secreting adenomas in six cases, and eight cases of adenoma without altered endocrine function. Five autopsy specimens were collected during the same period from patients of matching age that died from unrelated diseases and were included as normal anterior pituitar3, controls.
METHODS： Cell counts for positive immunohistochemical signals were recorded from histopathological sections. The percentage of positive cells was reported as a semi-quantitative analysis.
MAIN OUTCOME MEASURES： The rate of PPAR γ positive cells in different types of adenoma was based on hormonal levels and invasiveness of pituitary tumor cells.
RESULTS： All tumor biopsies were determined to express PPAR γ. The rate of PPAR γ -positive cells ranged between 8%-65% in the pituitary adenomas. According to hormonal type, PPAR γ expression did not vary between the groups. In addition, there was no significant difference in PPAR γ expression between the non-invasive and invasive pituitary adenomas.
CONCLUSIONS： Human pituitary adenom     

High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: implications for the pathophysiology of phenylketonuria

If left untreated, the common inherited metabolic disorder phenylketonuria (PKU) presents with mental retardation and reduced brain weight. The underlying molecular reasons for these deficits are unknown so far. Using human neuroblastoma cells as a model for normal human neuroblasts, elevated phenylalanine concentrations suppressed proliferation of these cells in culture. Furthermore, microarray and functional assays of these cells revealed that both phenylalanine and the known PPARγ agonist rosiglitazone regulated the same set of genes causing subsequently similar changes in the functional assays. The lowered brain weight of PKU patients may thus be the result of reduced neuroblast proliferation caused by phenylalanine-induced stimulation of PPARγ receptors. The observation that high concentrations of small substrates can activate receptors may serve as a new paradigm for other metabolic diseases and provides a new approach for the treatment of these disorders by application of specific receptor antagonists.     

Cyst formation and glial response in the brain lesions of stroke-prone spontaneously hypertensive rats

Summary The brain lesions in spontaneously hypertensive stroke-prone rats (SHRSP) are characterised by multifocal microvascular damage, breakdown of the blood-brain barrier, massive extravasation of plasma constitutents and severe brain oedema, with consequent spongy and cystic tissue destruction in the cerebral cortex and basal ganglia as well as loosening of the white matter. In this paper we analyse in greater detail the pathogenetic mechanisms by which the spongy and cystic lesions are formed and the response of astrocytic cells. For this purpose, tracer (Evans blue)-stained brain lesions were examined in 8-month-old SHRSP immunohistochemically and electron microscopically. Sponginess of the neuropil in small lesions and at the periphery of larger lesions was due to swollen neuronal and astrocytic cell processes, i.e.at this stage the oedema was mainly intracellular. Cystic lesions were formed in the grey matter both by expansion of the extracellular space (ECS) containing protein-rich ocdema fluid, and by rupture and subsequent loss of massively swollen cellular elements. In the white matter small slit-formed cysts along the fibre tracts were also formed by the expansion of ECS. In apparently recent lesions astrocytes displayed cytoplasmic oedema but otherwise were still fairly normal. In more chronic lesions increased numbers of enlarged astrocytes with prominent staining for glial fibrillary acidic protein were present. Their distribution corresponded well to the spread ofoedema, i.e. they were prominent around the leaky vessels in the grey matter, in the subpial zone and in the white matter. In the reparative phase the grey matter cysts became lined by astrocytic processes, a new glia limitans. Profuse sheets of glial processes in the neuropil around the cysts reestablished the compactness of the brain parenchyma.Supported by the Swedish Medical Research Council (Projects 12P-6827, 14X-4968, 12X-07123, and 12X-03020), the Finnish Medical Research Council, the Swedish National Association against Heart and Chest Diseases, the Medical Faculty, University of Lund and the MS-Fund     

Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis

Accumulating evidence suggests that inflammation plays a major role in the pathogenesis of motoneuron death in amyotrophic lateral sclerosis (ALS) both in humans and transgenic mouse models. Peroxisome proliferator-activated receptors (PPARs) are involved in the inflammatory process. Agonists of PPAR-alpha, -gamma, and -delta show anti-inflammatory effects both in vitro and in vivo. We investigated the therapeutic effect of pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, in the G93A SOD1 transgenic mouse model of ALS. Orally administered pioglitazone improved motor performance, delayed weight loss, attenuated motor neuron loss, and extended survival of G93A mice as compared to the untreated control littermate group. Pioglitazone treatment extended survival by 13%, and it reduced gliosis as assessed by immunohistochemical staining for CD-40 and GFAP. Pioglitazone also reduced iNOS, NFkappa-B, and 3-nitrotyrosine immunoreactivity in the spinal cords of G93A transgenic mice. These results suggest that pioglitazone may have therapeutic potential for human ALS.     

Blood-brain barrier leakage and brain edema in stroke-prone spontaneously hypertensive rats

Summary Brain edema associated with severe chronic hypertension was studied in stroke-prone spontaneously neously hypertensive rats (SHRSP), 5 to 9 months of age. Blood-brain barrier (BBB) leakage sites and intracerebral spreading pathways for plasma proteins were delineated by an intravenously (i.v.) injected exogenous dye tracer (Evans blue), known to form a complex with albumin in blood, and by immunohistochemical visualization of extravasated endogenous plasma proteins. The tissue content of edema fluid was estimated by measuring the specific gravity of selected brain regions, stained or unstained by the tracer dye, on a bromobenzene-kerosene gradient column. Multifocal BBB leakage sites were macroscopically detected within the cerebral cortex and the deep gray matter after i. v. circulation of Evans blue-albumin for 30 min. After 24 h of i.v. circulation the dye tracer had spread not only locally in the gray matter but also into the adjacent white matter, where it was widely distributed. Immunohistochemically visualized plasma proteins showed similar distribution. Unilateral superior cervical ganglionectomy performed at 4 weeks of age neither increased the incidence of major BBB opening to Evans blue-albumin nor altered the specific gravity of the ipsilateral cerebral hemisphere in grown-up SHRSP, furthermore, the blood pressure remained unchanged. The lack of significant effect on BBB function may possibly be attributed to the extensive reinnervation of the cerebral arteries, verified in the grown-up SHRSP using the Falck-Hillarp fluorescence method for visualization catecholaminergic nerve fibers. In SHRSP raised on a low-protein and high-salt diet the mean arterial blood pressure was 212 mm Hg compared to 195 mm Hg in controls (P<0.05) and the incidence of BBB opening was 72% compared to 25% in controls (P<0.05). After 24 h of i.v. circulation of Evans blue-albumin, brain regions stained by the dye tracer showed significantly reduced specific gravity (P<0.001), while unstained regions had normal values. Thus the brain edema fluid spread, as revealed by specific gravity measurements, corresponded to the intracerebral distribution of extravasated plasma proteins.Supported by The Swedish Medical Research Council (Project 12P-6827, 12X-07123, 14X-4968, 14X-732), The Swedish National Association Against Heart and Chest Diseases, The Medical Faculty, University of Lund, The MS-fund, Elsa Schmitz' Fund for Neurological and Neurosurgical Research, Rut and Erik Hardebo's Foundation, Fredrik and Ingrid Thuring's Foundation