LCM Disease of the Adult Rat: Morphological Alterations of the Brain

Author(s):  
J. Löhler ◽  
G. Schwendemann ◽  
F. Lehmann-Grube
Author(s):  
Rossana Favorito ◽  
Antonio Monaco ◽  
Maria C. Grimaldi ◽  
Ida Ferrandino

The glial cells are positioned to be the first cells of the brain parenchyma to face molecules crossing the blood-brain barrier with a relevant neuroprotective role from cytotoxic action of heavy metals on the nervous system. Cadmium is a highly toxic metal and its levels in the environment are increasing due to industrial activities. This element can pass the blood-brain barrier and have neurotoxic activity. For this reason we have studied the effects of cadmium on the glial architecture in the lizard Podarcis siculus, a significant bioindicator of chemical exposure due to its persistence in a variety of habitats. The study was performed on two groups of lizards. The first group of P. siculus was exposed to an acute treatment by a single i.p. injection (2 mg/kg-BW) of CdCl2 and sacrificed after 2, 7 and 16 days. The second one was used as control. The histology of the brain was studied by Hematoxylin/Eosin and Cresyl/Violet stains while the glial structures were analyzed by immunodetection of the glial fibrillary acidic protein (GFAP), the most widely accepted marker for astroglial cells. Evident morphological alterations of the brain were observed at 7 and 16 days from the injection, when we revealed also a decrease of the GFAP-immunopositive structures in particular in the rhombencephalic ventricle, telencephalon and optic tectum. These results show that in the lizards an acute exposure to cadmium provokes morphological cellular alterations in the brain but also a decrement of the expression of GFAP marker with possible consequent damage of glial cells functions.


Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.


1995 ◽  
Vol 79 (1) ◽  
pp. 136-140 ◽  
Author(s):  
S. I. Harik ◽  
W. D. Lust ◽  
S. C. Jones ◽  
K. L. Lauro ◽  
S. Pundik ◽  
...  

Hypobaric hypoxia at one-half atmospheric pressure for 3 wk was reported to increase the brain capillary density and glucose transport at the blood-brain barrier in the adult rat. We examined the metabolic concomitants of these alterations in rats subjected to the same hypoxic insult. Hypoxic rats increased brain glucose and lactate concentrations and decreased brain glycogen. However, hypoxia had no significant effects on regional brain levels of ATP and phosphocreatine or on intracellular pH, indicating successful adaptation to the hypoxic insult. 2-Deoxyglucose studies showed that hypoxia increased the regional metabolic rate for glucose by 10–40%. These results indicate increased glycolysis in the hypoxic rat brain, which probably underlies the increased density of glucose transporters in brain microvessels and the increased blood-to-brain glucose influx in hypoxia.


Author(s):  
А. М. Романюк ◽  
Г. Ю Будко

ОСОБЛИВОСТІ МАСОМЕТРИЧНИХ ПОКАЗНИКІВ ТА МОРФОЛОГІЧНИХ ЗМІН ГОЛОВНОГО МОЗКУ СТАТЕВОЗРІЛИХ ЩУРІВ В УМОВАХ ВПЛИВУ НА ОРГАНІЗМ СУЛЬФАТІВ МІДІ, ЦИНКУ ТА ЗАЛІЗА - З метою вивчення масометричних показників щурів та їх головного мозку за умов довготривалої дії (упродовж 90 діб) на організм сульфатів міді, цинку та заліза було проведено експеримент на 48 білих статевозрілих щурах-самцях масою 200-250 г віком 5-7 місяців. Застосовували анатомічні, статистичні та загальноприйняті методики мікроанатомічного методу дослідження. Встановлено, що комбінований вплив на організм сульфатів міді цинку та заліза чинить на головний мозок досить виражений токсичний ефект, що негативно позначається на масометричних показниках загальної маси щурів та маси головного мозку. Це свідчить про розвиток у головному мозку явищ гострого набряку з ознаками геморагічної інфільтрації. Ступінь вираження набряку зростає та досягає максимальних показників наприкінці експерименту.<br />ОСОБЕННОСТИ МАСОМЕТРИЧЕСКИХ ПОКАЗАТЕЛЕЙ И МОРФОЛОГИЧЕСКИХ ИЗМЕНЕНИЙ ГОЛОВНОГО МОЗГА ПОЛОВОЗРЕЛЫХ КРЫС В УСЛОВИЯХ ВОЗДЕЙСТВИЯ НА ОРГАНИЗМ СУЛЬФАТОВ МЕДИ, ЦИНКА И ЖЕЛЕЗА - С целью изучения масометрических показателей крыс и их головного мозга в условиях длительного действия (в течение 90 суток) на организм сульфатов меди, цинка и железа был проведен эксперимент на 48 белых половозрелых крысах-самцах массой 200250 г в возрасте 5-7 месяцев. Применялись анатомические, статистические и общепринятые методики микроанатомического метода исследования. Установлено, что комбинированное воздействие на организм сульфатов меди и цинка и железа оказывает на мозг достаточно выразительный токсический эффект, что отрицательно сказывается на массометрических показателях общего веса крыс и веса головного мозга. Это свидетельствует о развитии в головном мозге явлений острого отека с признаками геморрагической инфильтрации, степень выраженности которого максимальна в конце эксперимента.<br />FEATURES OF MASS INDICES AND MORPHOLOGICAL CHANGES IN ADULT RAT BRAIN UNDER THE INFLUENCE ON THE BODY OF COPPER SULFATE, ZINC AND IRON - To study the performance of rats and their mass brain in long acting (for 90 days) on the body of copper sulfate, zinc and iron, an experiment was conducted on 48 white adult male rats weighing 200-250 gram, aged 5-7 months. There was applied anatomy, statistics and conventional techniques microanatomical research method. It was established that the combined effect on the body of copper and zinc sulphates and iron in the brain has enough expressive toxicity, which affects performance on the total weight of the rats and brain weight. This testifies to the development of brain edema, acute phenomena with signs of hemorrhagic infiltration. The severity of edema increases and reaches maximum performance at the end of the experiment.<br />Ключові слова: головний мозок, солі важких металів, відносна маса, коефіцієнт цефалізації.<br />Ключевые слова: головной мозг, соли тяжелых металлов, относительная масса, коэффициент цефа- лизации.<br />Key words: brain, salts of heavy metals, relative mass, ratio cephalization.


2018 ◽  
Vol 69 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Nasim Vousooghi ◽  
Mitra‐Sadat Sadat‐Shirazi ◽  
Payam Safavi ◽  
Ramin Zeraati ◽  
Ardeshir Akbarabadi ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 240 ◽  
Author(s):  
Keiko Kobayashi ◽  
Yanchen Liu ◽  
Hiroshi Ichikawa ◽  
Shigekazu Takemura ◽  
Yukiko Minamiyama

We investigated the effect of bisphenol A (BPA) on oxidative stress and tau-related proteins in adult rat brains. BPA (10 mg/L) was administered to rats for eight weeks through their drinking water. The reactive oxygen species (ROS) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks. In the hippocampus, four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 (PARK7). The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment. The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK increased after eight weeks of BPA; the elevation could be related to tau phosphorylation. Protein phosphatase 2A (PP2A) in the hippocampus decreased after eight weeks of BPA treatment. At that time, SOD1 was significantly induced, but no changes in SOD2 expression were apparent in the hippocampus. Furthermore, the ratio of phosphorylated-tau (PHF-1, Ser396/ Ser404) to total tau level did not change. However, PHF-1 or other sites of tau could be phosphorylated after eight weeks in the hippocampi of rats. BPA induced systemic oxidative stress and could change ROS-induced signaling pathways in the brain. These results suggest that mitochondrial dysfunction possibly is not responsible for oxidative stress and neurodegeneration due to low doses of BPA.


2000 ◽  
Vol 78 (3) ◽  
pp. 237-243 ◽  
Author(s):  
Hao Shen ◽  
Krishna G Peri ◽  
Xing-Fei Deng ◽  
Sylvain Chemtob ◽  
Daya R Varma

Distribution of α1-adrenoceptor (α1AR) subtype (α1A, α1B, α1D) proteins in brain, heart, kidney, and liver of 1-week-old rats and in brain, heart, aorta, kidney, liver, vas deferens, prostate, and adrenal glands of adult rats was investigated by Western analysis, using receptor subtype specific polyclonal antibodies. High levels of immunoreactive α1AAR and α1DAR in brain and heart and of α1BAR in liver and heart of neonatal rats were detected. In adult rat tissues, the abundance of α1AAR protein was most marked in the brain, intermediate in heart, aorta, liver, vas deferens, and adrenals, and minimal in the kidney and prostate; relative to other tissues, the expression of α1BAR was higher in brain and heart and that of α1DAR in brain. All the three receptor subtypes increased with age in the brain cortex, whereas the abundance of α1BAR increased in the heart but decreased in the liver; α1AAR and α1DAR in liver, kidney, and heart were not affected by age. It is concluded that α1AR subtypes are widely expressed in different neonatal and adult rat tissues.Key words: α1A-adrenoceptors, α1B-adrenoceptors, α1D-adrenoceptors, α1-adrenoceptor proteins.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Susanne Nikolaus ◽  
Hans-Jörg Wittsack ◽  
Frithjof Wickrath ◽  
Anja Müller-Lutz ◽  
Hubertus Hautzel ◽  
...  

Abstract D-cycloserine (DCS) and amantadine (AMA) act as partial NMDA receptor (R) agonist and antagonist, respectively. In the present study, we compared the effects of DCS and AMA on dopamine D2/3R binding in the brain of adult rats in relation to motor behavior. D2/3R binding was determined with small animal SPECT in baseline and after challenge with DCS (20 mg/kg) or AMA (40 mg/kg) with [123I]IBZM as radioligand. Immediately post-challenge, motor/exploratory behavior was assessed for 30 min in an open field. The regional binding potentials (ratios of the specifically bound compartments to the cerebellar reference region) were computed in baseline and post-challenge. DCS increased D2/3R binding in nucleus accumbens, substantia nigra/ventral tegmental area, thalamus, frontal, motor and parietal cortex as well as anterodorsal and posterior hippocampus, whereas AMA decreased D2/3R binding in nucleus accumbens, caudateputamen and thalamus. After DCS, ambulation and head-shoulder motility were decreased, while sitting was increased compared to vehicle and AMA. Moreover, DCS increased rearing relative to AMA. The regional elevations of D2/3R binding after DCS reflect a reduction of available dopamine throughout the mesolimbocortical system. In contrast, the reductions of D2/3R binding after AMA indicate increased dopamine in nucleus accumbens, caudateputamen and thalamus. Findings imply that, after DCS, nigrostriatal and mesolimbic dopamine levels are directly related to motor/exploratory activity, whereas an inverse relationship may be inferred for AMA.


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