Expression of GFRα-1, receptor for GDNF, in rat brain capillary during postnatal development of the BBB

2000 ◽  
Vol 279 (2) ◽  
pp. C361-C368 ◽  
Author(s):  
Hiroyuki Utsumi ◽  
Hideki Chiba ◽  
Yasuhiro Kamimura ◽  
Makoto Osanai ◽  
Yo Igarashi ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Evans Blue ◽  
Brain Cortex ◽  
Reciprocal Relation ◽  
Adult Rats ◽  
Brain Capillary ◽  
Old Rats ◽  
Porcine Endothelial Cells ◽  
The Brain ◽  
Junction Proteins

It is well known that the blood-brain barrier (BBB) matures at ∼2 wk after birth in the rat. Recently, we showed that glial cell line-derived neurotrophic factor (GDNF) enhances the barrier function of porcine endothelial cells forming the BBB in culture. In the present study, we examined the relation between permeability of the BBB, using Evans blue as a tracer, and expression of the GDNF family receptor (GFRα-1) during postnatal development of the BBB. Morphometric analysis showed that exudation of Evans blue from capillaries of the cerebral cortex progressively decreased until postnatal day 21. Inversely, immunohistochemical examinations showed expression of GFRα-1 in the capillaries at postnatal day 3 and expression that reached the same levels as observed in adult rats by postnatal day 10. However, c- ret, which is thought to mediate a signal evoked by binding of GDNF to GFRα-1, was not expressed in the capillaries of the brain cortex in 3-mo-old rats. On the other hand, the tight junction proteins occludin and ZO-1 appeared to be fully expressed at birth. The reciprocal relation between GFRα-1 expression and the permeability of the BBB strongly suggests active participation of GDNF in postnatal development of the BBB, although the mechanism(s) involved is still veiled.

Distribution of α1-adrenoceptor subtype proteins in different tissues of neonatal and adult rats

2000 ◽  
Vol 78 (3) ◽  
pp. 237-243 ◽  
Author(s):  
Hao Shen ◽  
Krishna G Peri ◽  
Xing-Fei Deng ◽  
Sylvain Chemtob ◽  
Daya R Varma
Keyword(s):  
Vas Deferens ◽  
Polyclonal Antibodies ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Rat Tissues ◽  
Adult Rats ◽  
Adult Rat ◽  
Old Rats ◽  
Kidney Liver ◽  
The Brain

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.

scholarly journals Effect of phenylpyruvate on enzymes involved in fatty acid synthesis in rat brain

1973 ◽  
Vol 134 (2) ◽  
pp. 545-555 ◽  
Author(s):  
John M. Land ◽  
John B. Clark
Keyword(s):  
Fatty Acid ◽  
Citrate Synthase ◽  
Mitochondrial Protein ◽  
Fatty Acid Synthetase ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Adult Rats ◽  
Malonyl Coa ◽  
Old Rats ◽  
The Brain

1. The activities of, and the effects of phenylpyruvate on, citrate synthase (EC 4.1.3.7), acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthetase derived from the brains of 14-day-old and adult rats were investigated. 2. The brain citrate synthase from 14-day-old rats had a Km for oxaloacetate of 2.38μm and for acetyl-CoA of 16.9μm, and a Vmax. of 838nmol of acetyl-CoA incorporation/min per mg of mitochondrial protein. From adult rat brain this enzyme had a Km for oxaloacetate of 2.5μm and for acetyl-CoA of 16.6μm and a Vmax. of 1070nmol of acetyl-CoA incorporated/min per mg of mitochondrial protein. Phenylpyruvate inhibited the enzyme from adult and young rat brains in a competitive fashion with respect to acetyl-CoA, with a Ki of 700μm. 3. The brain acetyl-CoA carboxylase from 14-day-old rats had a Km for acetyl-CoA of 21μm and a Vmax. of 0.248nmol/min per mg of protein, and from adult rats a Km for acetyl-CoA of 21μm and a Vmax. of 0.173nmol/min per mg of protein. The enzyme from young and adult rats required citrate (Ka=3mm) for activation and were inhibited non-competitively by phenylpyruvate, with a Ki of 10mm. 4. The brain fatty acid synthetase from 14-day-old rats had a Km for acetyl-CoA of 7.58μm and a Vmax. of 1.1 nmol of malonyl-CoA incorporated/min per mg of protein, and from adult rats a Km for acetyl-CoA of 4.9μm and a Vmax. of 0.48nmol of malonyl-CoA incorporated/min per mg of protein. Phenylpyruvate acted as a competitive inhibitor with respect to acetyl-CoA with a Ki of 250μm for the enzyme from 14-day-old rats. 5. These results are discussed with respect to phenylketonuria, and it is suggested that the inhibition of the brain fatty acid synthetase and possibly the citrate synthetase by phenylpyruvate could explain the defective myelination characteristic of this condition.

Capillary perfusion during incomplete forebrain ischemia and reperfusion in rat brain

1993 ◽  
Vol 265 (2) ◽  
pp. H642-H648 ◽  
Author(s):  
H. Theilen ◽  
H. Schrock ◽  
W. Kuschinsky
Keyword(s):  
Rat Brain ◽  
Evans Blue ◽  
Ischemia Reperfusion ◽  
Experimental Models ◽  
Forebrain Ischemia ◽  
Capillary Perfusion ◽  
Experimental Conditions ◽  
Brain Capillary ◽  
Arterial Blood ◽  
The Brain

Previous studies have shown a complete plasma perfusion of all capillaries in the rat brain under normal physiological conditions. This raises the question under which experimental conditions nonperfused capillaries may show up in the brain. Two experimental models were investigated in rats. 1) Reduced cerebral blood flow (CBF) during incomplete forebrain ischemia: hemorrhagic hypotension was maintained for 30 min at a mean arterial blood pressure of 41 mmHg. During the final 5 min of hypotension both carotid arteries were ligated. 2) Reperfusion after incomplete forebrain ischemia: reperfusion lasted for 4 h after either 15 or 30 min of incomplete forebrain ischemia. Under both experimental conditions, the density of the existing as well as the plasma-perfused brain capillary network was quantified using fluorescent double staining. Local CBF was measured during incomplete forebrain ischemia using the quantitative autoradiographic 4-iodo-[N-methyl-14C]antipyrine technique. The results showed a decrease in CBF during incomplete forebrain ischemia, which amounted up to 94%. Whereas normotensive control animals showed a complete staining of all capillaries within 5 s after the intravenous injection of Evans blue, this period of time was increased to 10 s during incomplete forebrain ischemia, indicating a delayed capillary perfusion. Four hours of reperfusion after 15 min of incomplete forebrain ischemia resulted in a complete capillary staining, whereas reperfusion after 30 min of ischemia was followed by intracerebral bleedings and a few nonperfused capillary areas (circulation time of Evans blue: 10 s).(ABSTRACT TRUNCATED AT 250 WORDS)

Flow-independent heterogeneity of brain capillary plasma perfusion after blood exchange with a Newtonian fluid

1997 ◽  
Vol 272 (4) ◽  
pp. H1833-H1837 ◽  
Author(s):  
J. Vogel ◽  
K. F. Waschke ◽  
W. Kuschinsky
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Evans Blue ◽  
Microvascular Perfusion ◽  
Bovine Hemoglobin ◽  
Brain Capillary ◽  
Arterial Pco2 ◽  
Transit Times ◽  
Blood Exchange ◽  
The Brain

Previous studies from our group have indicated a heterogeneity of plasma transit times in brain capillaries. The heterogeneity was decreased with increasing cerebral blood flow during hypercapnia. In the present study, the hypothesis was tested that these apparent changes in microvascular plasma perfusion heterogeneity depend on the existence of red blood cells (RBC). To this end, the blood of anesthetized and paralyzed rats was replaced by a shear rate-independent oxygen-carrying substitute, ultrapurified polymerized bovine hemoglobin (UPBHB). Cerebral blood flow ([14C]iodoantipyrine technique) or microvascular perfusion pattern (intravenous bolus injection of Evans blue and decapitation 3-4 s later) was measured. After exchange transfusion with UPBHB, cerebral blood flow still varied with arterial PCO2, whereas in contrast to the unexchanged condition, the heterogeneity of the intracapillary Evans blue concentration remained unchanged. Compared with the unexchanged normocapnic condition, the heterogeneity of intracapillary dye concentration was decreased by one-quarter. It is concluded that RBC contribute to the microvascular perfusion heterogeneity in the brain.

The effect of vascular peptide bioregulator on microcirculation in the brain cortex of old rats

2016 ◽  
Vol 6 (4) ◽  
pp. 328-332 ◽  
Author(s):  
I. B. Sokolova ◽  
I. V. Sergeev ◽  
G. A. Ryzhak ◽  
V. Kh. Khavinson
Keyword(s):  
Brain Cortex ◽  
Old Rats ◽  
The Brain ◽  
Vascular Peptide Bioregulator

scholarly journals Function and Biomarkers of the Blood-Brain Barrier in a Neonatal Germinal Matrix Haemorrhage Model

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1677
Author(s):  
Erik Axel Andersson ◽  
Eridan Rocha-Ferreira ◽  
Henrik Hagberg ◽  
Carina Mallard ◽  
Carl Joakim Ek
Keyword(s):  
Blood Brain Barrier ◽  
Brain Injuries ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Germinal Matrix ◽  
Blood Brain ◽  
Old Rats ◽  
The Brain ◽  
Tracer Experiments ◽  
Junction Proteins

Germinal matrix haemorrhage (GMH), caused by rupturing blood vessels in the germinal matrix, is a prevalent driver of preterm brain injuries and death. Our group recently developed a model simulating GMH using intrastriatal injections of collagenase in 5-day-old rats, which corresponds to the brain development of human preterm infants. This study aimed to define changes to the blood-brain barrier (BBB) and to evaluate BBB proteins as biomarkers in this GMH model. Regional BBB functions were investigated using blood to brain 14C-sucrose uptake as well as using biotinylated BBB tracers. Blood plasma and cerebrospinal fluids were collected at various times after GMH and analysed with ELISA for OCLN and CLDN5. The immunoreactivity of BBB proteins was assessed in brain sections. Tracer experiments showed that GMH produced a defined region surrounding the hematoma where many vessels lost their integrity. This region expanded for at least 6 h following GMH, thereafter resolution of both hematoma and re-establishment of BBB function occurred. The sucrose experiment indicated that regions somewhat more distant to the hematoma also exhibited BBB dysfunction; however, BBB function was normalised within 5 days of GMH. This shows that GMH leads to a temporal dysfunction in the BBB that may be important in pathological processes as well as in connection to therapeutic interventions. We detected an increase of tight-junction proteins in both CSF and plasma after GMH making them potential biomarkers for GMH.

scholarly journals Hypoxia-Induced Lipid Peroxidation in the Brain During Postnatal Ontogenesis

2012 ◽  
pp. S89-S101 ◽  
Author(s):  
H. RAUCHOVÁ ◽  
M. VOKURKOVÁ ◽  
J. KOUDELOVÁ
Keyword(s):  
Lipid Peroxidation ◽  
Hypobaric Hypoxia ◽  
Brain Cortex ◽  
Membrane Lipids ◽  
High Rate ◽  
Subcortical Structures ◽  
Short Term ◽  
Adult Rats ◽  
Lactate Dehydrogenase Activity ◽  
The Brain

Reactive oxygen species (ROS) are common products of the physiological metabolic reactions, which are associated with cell signaling and with the pathogenesis of various nervous disorders. The brain tissue has the high rate of oxidative metabolic activity, high concentration of polyunsaturated fatty acids in membrane lipids, presence of iron ions and low capacity of antioxidant enzymes, which makes the brain very susceptible to ROS action and lipid peroxidation formation. Membranes of brain cortex show a higher production of thiobarbituric acid-reactive substances (TBARS) in prooxidant system (ADP.Fe3+/NADPH) than membranes from the heart or kidney. Lipid peroxidation influences numerous cellular functions through membrane-bound receptors or enzymes. The rate of brain cortex Na+,K+-ATPase inhibition correlates well with the increase of TBARS or conjugated dienes and with changes of membrane fluidity. The experimental model of short-term hypoxia (simulating an altitude of 9000 m for 30 min) shows remarkable increase in TBARS in four different parts of the rat brain (cortex, subcortical structures, cerebellum and medulla oblongata) during the postnatal development of Wistar rat of both sexes. Young rats and males are more sensitive to oxygen changes than adult rats and females, respectively. Under normoxia or hypobaric hypoxia both ontogenetic aspects and sex differences play a major role in establishing the activity of erythrocyte catalase, which is an important part of the antioxidant defense of the organism. Rats pretreated with L-carnitine (and its derivatives) have lower TBARS levels after the exposure to hypobaric hypoxia. The protective effect of L-carnitine is comparable with the effect of tocopherol, well-known reactive species scavenger. Moreover, the plasma lactate increases after a short-term hypobaric hypoxia and decreases in L-carnitine pretreated rats. Acute hypobaric hypoxia and/or L-carnitine-pretreatment modify serum but not brain lactate dehydrogenase activity. The obtained data seem to be important because the variations in oxygen tension represent specific signals of regulating the activity of many specific systems in the organism.

Differential adrenergic regulation of rat pineal cyclic AMP production and N-acetyltransferase activity during postnatal development: involvement of G alpha s and G alpha i1-2 proteins

1997 ◽  
Vol 155 (2) ◽  
pp. 305-312
Author(s):  
A Harmouch ◽  
JM Guerrero ◽  
D Pozo ◽  
M Rafii-el-Idrissi ◽  
RJ Reiter ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Postnatal Development ◽  
Adrenergic Receptors ◽  
Beta Adrenergic Receptors ◽  
Adult Rats ◽  
Beta Adrenergic ◽  
Young Rats ◽  
Old Rats ◽  
Gs Alpha ◽  
Rat Pineal Gland

We have studied why rat pineal N-acetyltransferase (NAT) activity is relatively insensitive to isoproterenol in young rats when compared with adult rats. We report that activation by isoproterenol of pineal cyclic AMP production and NAT activity is higher in adult than in 2-week-old rats. However, the effect of dibutyryl cyclic AMP, which enters the pinealocyte and duplicates the effect of cyclic AMP, on NAT activity was similar at both ages. Moreover, we found that both alpha- and beta-adrenergic receptors are highly specific at both ages, since the binding of the specific radioligands used to their receptors could be displaced only by their corresponding agonists and antagonists. However, we observed differences between pineals from young and adult rats when several families of the alpha subunit of G-proteins were studied in cell membranes. ADP-ribosylation and immunoblot studies have shown clear differences in both 42 and 45 kDa forms of the Gs alpha Both forms exhibit low values in pineals from 2-week-old animals when compared with 6-week-old. We also show that the later appearance of both Gs alpha forms is roughly similar to the potent activation of cyclic AMP production and NAT activity in adult rats when compared with young rats. In conclusion, the results presented suggest that the relative lack of sensitivity of rat pineal gland to beta-adrenergic receptor agonists early in the postnatal development may be explained by the low levels of membrane Gs alpha, rather than postreceptor-mediated mechanisms or changes in the characteristics of the beta-adrenergic receptors on the pinealocyte membrane.

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