scholarly journals Increased Brain Interstitial Fluid Adenosine Concentration during Hypoxia in Newborn Piglet

1987 ◽  
Vol 7 (2) ◽  
pp. 178-183 ◽  
Author(s):  
T. S. Park ◽  
David G. L. Van Wylen ◽  
Rafael Rubio ◽  
Robert M. Berne
Keyword(s):  
Frontal Cortex ◽  
Interstitial Fluid ◽  
Acute Hypoxia ◽  
Newborn Piglet ◽  
Cisterna Magna ◽  
Hypoxic Conditions ◽  
Adenosine Concentration ◽  
Brain Dialysis ◽  
The Brain ◽  
Dialysis Technique

The effects of arterial hypoxia on interstitial fluid adenosine concentrations were studied in the frontal cortex and thalamus by the brain dialysis technique and in CSF from the cisterna magna of the newborn piglet. Acute hypoxia (PaO2 = 20 ± 1 mm Hg) increased the interstitial fluid adenosine concentrations significantly from 0.68 ± 0.29 (SEM) to 1.60 ± 0.35 μ M in the frontal cortex and from 1.03 ± 0.32 to 2.60 ± 0.86 μ M in the thalamus (n = 8). Interstitial fluid inosine and hypoxanthine also increased significantly during hypoxia. In separate groups of piglets, the adenosine concentration in the cisterna magna CSF under normoxic conditions was 0.04 ± 0.01 μ M (n = 5), which increased significantly to 0.17 ± 0.04 μ M (n = 6) with hypoxia (PaO2 = 4.7 ± 1.2 mm Hg). Cisterna magna CSF inosine levels did not change significantly during the severe hypoxia. Adenosine concentrations found in the interstitial space and CSF of newborn piglets under normoxic and hypoxic conditions are within the vasodilator range. These results thus suggest that in the neonatal brain adenosine may play a role in regulating blood flow during hypoxia.

scholarly journals Brain Interstitial Adenosine and Sagittal Sinus Blood Flow during Systemic Hypotension in Piglet

1988 ◽  
Vol 8 (6) ◽  
pp. 822-828 ◽  
Author(s):  
T. S. Park ◽  
David G. L. Van Wylen ◽  
Rafael Rubio ◽  
Robert M. Berne
Keyword(s):  
Blood Flow ◽  
Interstitial Fluid ◽  
Cerebrovascular Resistance ◽  
Sagittal Sinus ◽  
Group 4 ◽  
Brain Dialysis ◽  
Group 3 ◽  
Group 2 ◽  
The Brain ◽  
Dialysis Technique

We sampled, using the brain dialysis technique, interstitial fluid adenosine from the frontal cortex of newborn piglets subjected to hemorrhagic hypotension while measuring sagittal sinus blood flow, cerebrovascular resistance (CVR), and cerebral O2 delivery. In group 1 (n = 8), MABP was reduced in successive steps from 76 to 30 mm Hg with decrements of ∼ 10 mm Hg. At 60 mm Hg, CVR decreased by 19% (p < 0.001), but sagittal sinus blood flow and interstitial fluid adenosine remained unchanged. At 50 mm Hg, both sagittal sinus blood flow and CVR decreased by 19% (p < 0.001) and interstitial fluid adenosine rose 4.7-fold (p < 0.05). At 40 and 30 mm Hg, sagittal sinus blood flow decreased further but CVR remained steady, whereas interstitial fluid adenosine rose 10- and 16-fold, respectively. In group 2 (n = 7), an abrupt reduction of MABP from 80 to 47 mm Hg produced no change in sagittal sinus blood flow and a 29% decrease in CVR (p < 0.01). Interstitial fluid adenosine increased twofold (p < 0.01). In group 3 (n = 7), an abrupt reduction of MABP from 79 to 40 mm Hg decreased sagittal sinus blood flow and CVR by 24 and 30%, respectively (p < 0.01). Interstitial fluid adenosine rose threefold (p < 0.01). In groups 1, 2, and 3, the increases in interstitial fluid adenosine accompanied decreases in cerebral O2 delivery. In group 4 (n = 7), artificial CSF with a Po2 of 152 mm Hg was perfused through the brain dialysis cannula during graded hypotension. In this group, interstitial fluid adenosine rose only at an MABP of 20 mm Hg. These data support the concept that adenosine participates in the regulation of CBF during hypotension in piglets.

scholarly journals Increases in Cerebral Interstitial Fluid Adenosine Concentration during Hypoxia, Local Potassium Infusion, and Ischemia

1986 ◽  
Vol 6 (5) ◽  
pp. 522-528 ◽  
Author(s):  
David G. L. Van Wylen ◽  
T. S. Park ◽  
Rafael Rubio ◽  
Robert M. Berne
Keyword(s):  
Interstitial Fluid ◽  
External Medium ◽  
Oxygen Demand ◽  
In Vitro Tests ◽  
Artificial Cerebrospinal Fluid ◽  
Adenosine Concentration ◽  
The Brain ◽  
Dialysis Technique

This study used the brain dialysis technique to test the hypothesis that the adenosine concentration of cerebral interstitial fluid increases during situations in which cerebral oxygen supply is inadequate for oxygen demand. Sealed 300-μm hollow dialysis fibers were implanted in the caudate nucleus of pentobarbital-anesthetized rats and perfused at 2 μl/min with artificial cerebrospinal fluid. In vitro tests indicated the recovery of adenosine, inosine, and hypoxanthine from the external medium to be ∼20% at 2 μl/min and close to 100% at 0.1 μl/min. Three in vivo interventions were tested: hypoxia/hypotension (Pao2 = 41.9 mm Hg; MABP = 42.8 mm Hg; n = 9), local potassium infusion (n = 4), and cerebral anoxia/ischemia (n = 10). These interventions produced 10-, 4-, and 30-fold increases in perfusate adenosine concentration, respectively, as well as increases in perfusate concentrations of inosine and hypoxanthine. A separate group of rats (n = 9) perfused at 0.1 μl/min yielded estimates of cerebral interstitial fluid adenosine, inosine, and hypoxanthine concentrations of 1.26, 3.30, and 7.19 μ M, respectively. These results are consistent with the adenosine hypothesis for the regulation of CBF.

scholarly journals The Effect of Local Infusion of Adenosine and Adenosine Analogues on Local Cerebral Blood Flow

1989 ◽  
Vol 9 (4) ◽  
pp. 556-562 ◽  
Author(s):  
David G. L. Van Wylen ◽  
T. S. Park ◽  
Rafael Rubio ◽  
Robert M. Berne
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Receptor Activation ◽  
Local Cerebral Blood Flow ◽  
Caudate Nuclei ◽  
Adenosine Concentration ◽  
The Brain ◽  
Adenosine Receptor Activation ◽  
Dialysis Technique ◽  
Hydrogen Clearance

The purpose of this study was to determine the effects of local infusion of adenosine (ADO) and non-metabolized ADO analogues on local cerebral blood flow (CBF) and interstitial fluid (ISF) ADO levels. The brain dialysis technique was used to (a) deliver drugs locally to brain tissue, (b) estimate cerebral ISF ADO levels, and (c) measure local CBF (hydrogen clearance). Dialysis probes were implanted bilaterally in the caudate nuclei of ketamine-anesthetized rats. The probe on one side was perfused with artificial CSF while the contralateral probe was perfused with artificial CSF containing ADO ( n = 5), or the ADO agonists 2-chloroadenosine (2-CADO; n = 4) or 5'-N-ethylcarboxamide adenosine (NECA; n = 4). When ADO was included in the artificial CSF at 10−5, 10−4, or 10−3 M, a 30% increase in local CBF was detected only with 10−3 M ADO. During perfusion with ADO, dialysate inosine and hypoxanthine levels increased, indicating that the cells adjacent to the probe metabolized the exogenous ADO. With 2-CADO included in the artificial CSF at 10−6, 10−5, or 10−4 M, local CBF increased 18, 131, and 201%, respectively. Perfusion with artificial CSF containing 10−7, 10−6, or 10−5 M NECA resulted in a 35, 112, and 187% increase in local CBF, respectively. In a separate group of rats ( n = 6), perfusion with artificial CSF containing 10−6 M NECA resulted in a sustained twofold increase in local CBF and 40% decrease in dialysate adenosine concentration, both of which could be reversed by including 8-( p-sulfophenyl)-theophylline, an ADO receptor antagonist, in the artificial CSF. These results are consistent with the known vascular actions of ADO and ADO analogues and suggest that there is a basal level of ISF ADO that can be reduced by increased CBF and/or adenosine receptor activation.

scholarly journals Exercise-Induced Elevated BDNF Level Does Not Prevent Cognitive Impairment Due to Acute Exposure to Moderate Hypoxia in Well-Trained Athletes

2020 ◽  
Vol 21 (15) ◽  
pp. 5569 ◽  
Author(s):  
Zofia Piotrowicz ◽  
Małgorzata Chalimoniuk ◽  
Kamila Płoszczyca ◽  
Miłosz Czuba ◽  
Józef Langfort
Keyword(s):  
Acute Hypoxia ◽  
Negative Effects ◽  
Positive Effects ◽  
Hypoxic Conditions ◽  
Acute Elevation ◽  
Psychomotor Tasks ◽  
Exercise Induced ◽  
Response To Exercise ◽  
Cognition Impairment ◽  
The Brain

Exposure to acute hypoxia causes a detrimental effect on the brain which is also manifested by a decrease in the ability to perform psychomotor tasks. Conversely, brain-derived neurotrophic factor (BDNF), whose levels are elevated in response to exercise, is a well-known factor in improving cognitive function. Therefore, the aim of our study was to investigate whether the exercise under hypoxic conditions affects psychomotor performance. For this purpose, 11 healthy young athletes performed a graded cycloergometer exercise test to volitional exhaustion under normoxia and acute mild hypoxia (FiO2 = 14.7%). Before, immediately after exercise and after a period of recovery, choice reaction time (CRT) and number of correct reactions (NCR) in relation to changes in serum BDNF were examined. Additionally, other selected factors which may modify BDNF production, i.e., cortisol (C), nitrite, catecholamines (adrenalin-A, noradrenaline-NA, dopamine-DA, serotonin-5-HT) and endothelin-1 (ET-1), were also measured. Exercise in hypoxic conditions extended CRT by 13.8% (p < 0.01) and decreased NCR (by 11.5%) compared to rest (p < 0.05). During maximal workload, NCR was lower by 9% in hypoxia compared to normoxia (p < 0.05). BDNF increased immediately after exercise in normoxia (by 29.3%; p < 0.01), as well as in hypoxia (by 50.0%; p < 0.001). There were no differences in BDNF between normoxia and hypoxia. Considering the fact that similar levels of BDNF were seen in both conditions but cognitive performance was suppressed in hypoxia, acute elevation of BDNF did not compensate for hypoxia-induced cognition impairment. Moreover, neither potentially negative effects of C nor positive effects of A, DA and NO on the brain were observed in our study.

scholarly journals Effect of Dipyridamole on Cerebral Extracellular Adenosine Level in vivo

1990 ◽  
Vol 10 (3) ◽  
pp. 424-427 ◽  
Author(s):  
T. S. Park ◽  
Jeffrey M. Gidday
Keyword(s):  
Cerebral Ischemia ◽  
Frontal Cortex ◽  
Extracellular Adenosine ◽  
Twofold Increase ◽  
Control Side ◽  
Transport Inhibitor ◽  
Adenosine Concentration ◽  
Brain Dialysis ◽  
Adenosine Transport

The effect of dipyridamole, an adenosine transport inhibitor, on cerebral extracellular adenosine concentration remains to be determined. To examine this issue, bilateral brain dialysis samples were obtained from piglet frontal cortex before, during, and after 5 min of cerebral ischemia; 10−4 M dipyridamole was administered through one dialysis probe. On the control side, dialysate adenosine concentration increased 5.7-fold during ischemia and 15-fold during the first 5 min of reperfusion; it returned to control levels after 15 min of reperfusion. Relative to the control side, dipyridamole caused a twofold increase in basal dialysate adenosine concentration and increased dialysate adenosine concentration at 10 and 15 min of reperfusion, but no increase in dialysate adenosine occurred during and immediately after ischemia. The results indicate that, in the piglet brain, cerebral ischemia markedly elevates intracerebral extracellular adenosine concentration and that dipyridamole increases extracellular adenosine levels.

Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

2016 ◽  
Vol 21 (2) ◽  
pp. 28-37
Author(s):  
Oscar Solís-Salgado ◽  
José Luis López-Payares ◽  
Mauricio Ayala-González
Keyword(s):  
Amyloid Beta ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Bulk Flow ◽  
Polyethylene Glycols ◽  
Brain Interstitial Fluid ◽  
El Sistema ◽  
Arterial Pulsation ◽  
The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

scholarly journals Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line

2021 ◽  
Vol 11 (4) ◽  
pp. 308
Author(s):  
Valentina Bravatà ◽  
Walter Tinganelli ◽  
Francesco P. Cammarata ◽  
Luigi Minafra ◽  
Marco Calvaruso ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Line ◽  
Acute Hypoxia ◽  
Hypoxic Condition ◽  
Biological Processes ◽  
Microarray Gene Expression ◽  
Hypoxic Conditions ◽  
Gene Expression Analyses ◽  
Shed Light ◽  
New Strategies

In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.

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