Abstract W MP75: Docosahexaenoic Acid Upregulates Iduna Expression in the Ischemic Penumbra and Protects Rat Brains Against Focal Ischemia

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Nicolas G Bazan ◽  
Pranab K Mukherjee ◽  
Veronica Balaszczuk ◽  
Larissa Khoutorova ◽  
Daniela V Anzola ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Docosahexaenoic Acid ◽  
Western Blot ◽  
Time Course ◽  
Ring Finger ◽  
Blood Gases ◽  
Glutamate Excitotoxicity ◽  
Experimental Stroke ◽  
Ischemic Penumbra ◽  
Arterial Blood

Introduction: Ring finger protein 146, also called Iduna, has been identified, as a neuroprotective protein. Iduna facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or cerebral ischemia. Recently, we have shown that docosahexaenoic acid (DHA; 22:6n-3) therapy improves functional and histological outcomes following experimental stroke. This study evaluated the time course expression of Iduna in the ischemic penumbra and the role of DHA in cerebral ischemia and its potential mechanism. METHODS: Thirty-six male SD rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. DHA (5 mg/kg) or vehicle (saline) was administered IV at 3 h after the onset of MCAo and animals were sacrificed on days 1, 3 and 7 (n=6 rats per group). The neurological function was evaluated during occlusion (60 min), and on days 1, 3 and 7 after MCAo; a grading scale of 0-12 was employed (0=normal and 12=maximal deficit). Western blot and double immunostaining (Iduna/NeuN and Iduna/GFAP) were used to analyze Iduna expression in the ischemic penumbra on days 1, 3 and 7. RESULTS: All animals showed similar values for rectal and cranial temperatures, arterial blood gases, and plasma glucose during and after MCAo. Behavioral deficit was significantly improved by treatment with DHA compared to vehicle on days 1 (by 30%), 3 (by 31%) and 7 (by 32%). Western-blot analysis showed that DHA treatment increased Iduna expression in the ischemic penumbra compared to vehicle on day 1 (2.2±0.3 vs. 0.6±0.1) and day 3 (0.44±0.05 vs. 0.3±0.01, respectively). There were no differences in Iduna expression on day 7 between DHA and vehicle-treated groups (0.33±0.02 and 0.35±0.02). Immunostaining revealed that Iduna expression was increased in the penumbra of DHA-treated rats. Conclusions: DHA protected the brain from severe damage caused by MCAo. This effect may be through upregulation of Iduna expression in the ischemic penumbra. Thus, it is reasonable to hypothesize that DHA has potential for the effective treatment of ischemic stroke in patients.

Age-related cerebrovascular response to global ischemia in pigs

1990 ◽  
Vol 259 (5) ◽  
pp. H1551-H1558
Author(s):  
J. R. Kirsch ◽  
M. A. Helfaer ◽  
K. Blizzard ◽  
T. J. Toung ◽  
R. J. Traystman
Keyword(s):  
Cerebral Ischemia ◽  
Vena Cava ◽  
Blood Gases ◽  
Hemoglobin Concentration ◽  
Brain Regions ◽  
Global Ischemia ◽  
Global Cerebral Ischemia ◽  
Arterial Oxygen ◽  
Arterial Blood ◽  
Age Related

We tested the hypothesis that 1- to 2-wk-old pigs (piglet) have improved recovery of cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and somatosensory-evoked potentials (SEP) compared with 6- to 8-mo-old pigs (pig) after transient global cerebral ischemia. All animals were anesthetized with pentobarbital sodium. After tracheostomy ventilation was adjusted to maintain normoxia (arterial oxygen pressure, 100-150 mmHg) and normocarbia (arterial carbon dioxide pressure, 35-40 mmHg). Arterial blood gases, blood pressure, and hemoglobin concentration remained within physiological limits throughout the experiment. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta. During ischemia the electroencephalogram and SEP became isoelectric within 40 and 120 s, respectively. At 10 min of reperfusion hyperemia occurred in most brain regions (e.g., whole brain: piglet, 270 +/- 45%; pig, 316 +/- 48%). In pigs delayed hypoperfusion occurred in all regions except white matter. In contrast, piglets only had delayed hyperperfusion to the brain stem and caudate nucleus. Throughout reperfusion CMRO2 was decreased in pigs (3.3 +/- 0.4 to 1.9 +/- 0.2 ml.min-1.100 g-1) but was not different from control (2.7 +/- 0.3 ml.min-1.100 g-1) in piglets. By the end of reperfusion SEP amplitude was closer to control in piglets than pigs (55 +/- 9 vs. 32 +/- 4% of control). We conclude that 1- to 2-wk-old piglets have quicker return of CBF, CMRO2, and SEP to control values after global ischemia, which mechanistically may explain previous reports of improved neurological recovery in young animals after transient ischemia.

Effect of a single air dive on pulmonary diffusing capacity in professional divers

1993 ◽  
Vol 74 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Z. Dujic ◽  
D. Eterovic ◽  
P. Denoble ◽  
G. Krstacic ◽  
J. Tocilj ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Time Course ◽  
Blood Gases ◽  
Diffusing Capacity ◽  
Pulmonary Diffusing Capacity ◽  
Sequence Of Events ◽  
Arterial Blood ◽  
Bubble Detection ◽  
Venous Gas Embolism ◽  
Arterial Po2

The aim of this study was to determine whether venous gas embolism after a single air dive, evaluated using precordial Doppler monitoring, was associated with alterations in spirometry, lung volumes, arterial blood gases, or pulmonary diffusing capacity for carbon monoxide (DLCO). Postdive time course monitoring of pulmonary function was undertaken in 10 professional divers exposed to absolute air pressure of 5.5 bar for 25 min in a dry walk-in chamber. The US Navy decompression table was followed. Venous bubbles were detected by precordial Doppler monitoring. Two types of decompression were used: air and 100% O2 applied for 21 min during decompression stops. Spirometry, flow-volume, and body plethysmography parameters were unchanged after the dive with air decompression (AD) as well as with O2 decompression (OD). A significant reduction in arterial PO2, on average 20 Torr, was found after the dive with AD. DLCO was decreased in all divers 20, 40, 60, and 80 min after diving with AD (P < 0.001), whereas it was not significantly decreased after diving with OD. Maximal DLCO decrease of approximately 15% occurred 20 min postdive. In AD diving, maximum bubble grade for each individual vs. maximum DLCO reduction correlated significantly (r = 0.85, P = 0.002), as well as DLCO vs. arterial PO2 (r = 0.64, P = 0.017). In conclusion, a reduction in pulmonary diffusing capacity is observed in parallel with the appearance of venous bubbles detected by precordial Doppler. We suggest that bubbles cause pulmonary microembolization, triggering a complex sequence of events that remains to be resolved. Measuring DLCO complements Doppler bubble detection in postdiving assessment of pulmonary function.

scholarly journals α2-Adrenoceptors do not Mediate Neuroprotection in Acute Ischemic Stroke in Mice

2011 ◽  
Vol 31 (10) ◽  
pp. e1-e7 ◽  
Author(s):  
Marc Brede ◽  
Stefan Braeuninger ◽  
Friederike Langhauser ◽  
Lutz Hein ◽  
Norbert Roewer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Blood Pressure Lowering Effect ◽  
Α2 Adrenoceptors ◽  
Arterial Blood ◽  
Neuroprotective Function

We assessed the neuroprotective potential of α2-adrenoceptors in ischemic stroke using mice with targeted deletions of individual α2-adrenoceptor subtypes (α 2A−/−, α 2B−/−, α 2C−/−, α 2A/C−/−). The effects of the α2-adrenoceptor agonist clonidine were studied in parallel. Focal cerebral ischemia was induced with or without clonidine pretreatment by transient middle cerebral artery occlusion. Neurologic outcome and infarct volumes were evaluated on day 1. Cerebral blood flow (CBF) and mean arterial pressure were determined. α2- Adrenoceptor null mice did not display larger infarct volumes compared with wild-type (WT) mice under basal conditions ( P>0.05). In line with this finding, pretreatment with clonidine did not protect from ischemic brain damage in WT mice or α 2A−/−, α 2B−/−, and α 2C−/− mice. Clonidine induced smaller infarct volumes only in α 2A/C−/− mice ( P < 0.05), but this did not translate into improved neurologic function ( P > 0.05). Importantly, while clonidine caused a significant decrease in arterial blood pressure in all groups, it had no blood pressure lowering effect in α 2A/C−/− mice, and this correlated with higher CBF and smaller infarct volumes in this group. In summary, we could not demonstrate a neuroprotective function of α2-adrenoceptors in focal cerebral ischemia. Careful controlling of physiological parameters relevant for stroke outcome is recommended in experimental stroke studies.

scholarly journals Evaluation of the PBR/TSPO Radioligand [18F]DPA-714 in a Rat Model of Focal Cerebral Ischemia

2009 ◽  
Vol 30 (1) ◽  
pp. 230-241 ◽  
Author(s):  
Abraham Martín ◽  
Raphaël Boisgard ◽  
Benoit Thézé ◽  
Nadja Van Camp ◽  
Bertrand Kuhnast ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Pet Imaging ◽  
Time Course ◽  
Focal Cerebral Ischemia ◽  
Quantitative Information ◽  
Translocator Protein ◽  
Experimental Stroke ◽  
Tspo Expression

Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [18F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed significant increase in DPA ( N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. In vitro autoradiography confirmed these in vivo results. In vivo and in vitro [18F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [18F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.

Phosphatidylglycerol-deficient lung surfactant has normal properties

1983 ◽  
Vol 55 (2) ◽  
pp. 496-502 ◽  
Author(s):  
O. S. Beppu ◽  
J. A. Clements ◽  
J. Goerke
Keyword(s):  
Time Course ◽  
Lung Surfactant ◽  
Blood Gases ◽  
Electron Microscopic Examination ◽  
Normal Pressure ◽  
Lung Lavage ◽  
Fatty Acyl ◽  
Electron Microscopic ◽  
Rabbit Lung ◽  
Arterial Blood

We have investigated the effects of substituting phosphatidylinositol (PI) for phosphatidylglycerol (PG) on the functional properties of rabbit lung surfactant. We gave oral 10% glucose solution for 3 days to 11 rabbits and 10% inositol to 12 others. Lung lavage surfactant phospholipids were normal in both groups, except that PG was low and PI was high in the inositol group. Fatty acyl group distributions did not differ, except for a slight decrease of oleic acid in the inositol group. Electron microscopic examination showed normal surfactant structure in both. The time course of surfactant adsorption to an air-water interface was similar in both groups. Minimum surface tension after film compression was 4.0 +/- 0.8 mN . m-1 in the glucose group and 2.9 +/- 1.3 mN . m-1 in the inositol group (mean +/- SE). Surface potential-surface pressure isotherms were identical to within 12 mV. Arterial blood gases breathing air and 100% O2 were the same in both groups, as were pressure-volume curves of excised lungs, with both air and saline filling. The results suggest that, if acidic phospholipids are necessary for maintaining normal surfactant structure and surface properties, normal pressure-volume relationships, and normal gas exchange, then PI may substitute for PG.

Acidosis stimulates beta-endorphin release during exercise

1994 ◽  
Vol 77 (4) ◽  
pp. 1913-1918 ◽  
Author(s):  
D. V. Taylor ◽  
J. G. Boyajian ◽  
N. James ◽  
D. Woods ◽  
A. Chicz-Demet ◽  
...  
Keyword(s):  
High Intensity ◽  
Time Course ◽  
Base Excess ◽  
Healthy Adult ◽  
Blood Gases ◽  
Blood Levels ◽  
Adult Males ◽  
Constant Intensity ◽  
Beta Endorphin ◽  
Arterial Blood

Elevated blood levels of beta-endorphin have been associated with high-intensity exertion, but the stimulus for beta-endorphin release is unknown. Some studies of exercise have associated beta-endorphin release with increased exertion levels, but other evidence suggests that acidosis may stimulate the release of beta-endorphin. This study examines acidosis as a possible stimulus for beta-endorphin release by examining the effects of arterial blood gases, whole blood lactate, and respiratory changes on beta-endorphin levels and by examining the effects of buffering during exercise on these levels. Initially, seven healthy adult males were evaluated during incremental exercise. During incremental exertion, indicators of acidosis correlated with endorphin levels: pH (r = -0.94), PCO2 (r = -0.85), HCO3- (r = -0.88), base excess (r = -0.94), and lactate (r = 0.89). A multivariate model showed that beta-endorphin levels were predicted best by the change in base excess. A time course analysis showed that beta-endorphin responses peaked postexercise and paralleled blood acid levels. Subsequently, subjects were compared after alkali loading and placebo during constant-intensity exercise at 85% of maximal exertion to determine whether acidosis is necessary for endorphin release. Treatment with a buffer, which effectively maintained pH above 7.40, significantly suppressed endorphin release (F = 3.07; P < 0.0001). The results of this study indicate that acidosis rather than any other physiological change associated with high-intensity exertion is the primary stimulus for beta-endorphin release.

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia

1986 ◽  
Vol 60 (4) ◽  
pp. 1203-1208 ◽  
Author(s):  
J. Raynaud ◽  
D. Douguet ◽  
P. Legros ◽  
A. Capderou ◽  
B. Raffestin ◽  
...  
Keyword(s):  
Time Course ◽  
Venous Blood ◽  
Blood Gases ◽  
Arterial Blood ◽  
O2 Concentration ◽  
Rhythmic Exercise ◽  
Underlying Mechanisms ◽  
Arterial Po2 ◽  
Local Metabolism ◽  
Blood Data

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.

Effect of naloxone on cerebral perfusion and cardiac performance during experimental cerebral ischemia

1986 ◽  
Vol 64 (5) ◽  
pp. 780-786 ◽  
Author(s):  
Robert J. Hariri ◽  
Elizabeth L. Supra ◽  
John Paul Roberts ◽  
Michael H. Lavyne
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Cerebral Perfusion ◽  
Blood Gases ◽  
Experimental Stroke ◽  
Arterial Blood Gases ◽  
Content Type ◽  
Arterial Blood ◽  
Fine Print

✓ Transient global cerebral ischemia (TGI) was induced in awake rats using the “four-vessel” occlusion model of Pulsinelli and Brierley. Blood pressure, arterial blood gases, cerebral blood flow, and cardiac output were measured during the acute (up to 2 hours) and chronic (2 to 72 hours) postischemic time periods. Coincident with the onset of TGI, cardiac output and caudate blood flow were depressed. The former returned to baseline within 30 minutes after the conclusion of TGI, and the latter progressed to hyperemia at 12 hours (81.8 ± 4.9 vs 68.6 ± 3.9 ml/min/100 gm tissue (mean ± standard error of the mean)) and oligemia at 72 hours (45.5 ± 4.8 ml/min/100 gm tissue) post-TGI in the untreated control rats. Arterial blood gases and blood pressure were unchanged. Naloxone (1 mg/kg) given at the time of TGI or as late as 60 minutes post-TGI and every 2 hours thereafter for 24 hours or bilateral cervical vagotomy prevented the depression in cardiac output and blocked the hyperemic-oligemic cerebral blood flow pattern that was predictive of stroke in this rat model. Changes in cardiac output after TGI in this model appear to be mediated by parasympathetic pathways to the heart from the brain stem. Opiate receptor blockade probably blocks endogenous opioid peptide stimulation of these brain-stem circulatory centers, which results in inhibition of parasympathetic activity and improvement in cardiac output. The usefulness of naloxone in the treatment of experimental stroke may be a function of its ability to improve cerebral perfusion in pressure-passive cerebrovascular territories. Variations in cardiac output during experimental stroke may explain the dissimilar responses to naloxone treatment reported by other investigators of experimental stroke.

scholarly journals Time course and recovery of arterial blood gases during exacerbations in adults with Cystic Fibrosis

2009 ◽  
Vol 8 (1) ◽  
pp. 9-13 ◽  
Author(s):  
D.F. Waterhouse ◽  
A.M. McLaughlin ◽  
C.G. Gallagher
Keyword(s):  
Cystic Fibrosis ◽  
Time Course ◽  
Blood Gases ◽  
Arterial Blood Gases ◽  
Arterial Blood

Temporal relationships of ventilatory failure, pump failure, and diaphragm fatigue

1996 ◽  
Vol 81 (1) ◽  
pp. 238-245 ◽  
Author(s):  
C. S. Sassoon ◽  
S. E. Gruer ◽  
G. C. Sieck
Keyword(s):  
Time Course ◽  
Central Fatigue ◽  
Blood Gases ◽  
Respiratory Arrest ◽  
Peripheral Fatigue ◽  
Respiratory Drive ◽  
Pump Failure ◽  
Arterial Blood ◽  
Ventilatory Failure ◽  
Resistive Loads

The time course of ventilatory failure, pump failure, and diaphragm peripheral fatigue was determined during the application of external inspiratory resistive loads (IRL) in anesthetized rabbits. Pump failure is defined as the inability of the diaphragm to sustain the expected force under IRL. To assess contractile fatigue, transdiaphragmatic pressures (Pdi) generated by bilateral phrenic nerve stimulation at 75 Hz (Pdi-75) and 20 Hz (Pdi-20) were measured. The amplitude of evoked diaphragm electromyographic (EMG) signals was measured to assess neurotransmission failure. The rate of rise of spontaneous diaphragm EMG was used as an index of respiratory drive. Ventilation was evaluated together with arterial blood gases. During IRL the rate of rise of spontaneous diaphragm EMG increased, and there was a progressive hypercapnic acidosis and hypoxemia, indicating ventilatory failure. In contrast, Pdi-75 and Pdi-20 were stable until the time of respiratory arrest (apnea), when they decreased by 34 and 45%, respectively. The amplitude of evoked diaphragm EMG signals remained unchanged throughout the IRL and decreased only slightly at the time of apnea. We conclude that IRL induces progressive ventilatory failure long before any contractile fatigue of the diaphragm or pump failure occurs. This suggests that ventilatory failure is due to central fatigue, whereas pump failure (apnea) is attributable to multiple factors.

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