scholarly journals Ischemic Thresholds of Cerebral Protein Synthesis and Energy State following Middle Cerebral Artery Occlusion in Rat

1991 ◽  
Vol 11 (5) ◽  
pp. 753-761 ◽  
Author(s):  
G. Mies ◽  
S. Ishimaru ◽  
Y. Xie ◽  
K. Seo ◽  
K.-A. Hossmann
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Energy State ◽  
High Threshold ◽  
Atp Content ◽  
Mca Occlusion ◽  
Cerebral Protein Synthesis ◽  
Energy Failure

The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 μm resolution. Each 75 × 75 μm digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 ± 12.0 ml 100 g−1 min−1 and that of energy failure was 18.5 ± 9.8 ml 100 g−1 min−1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 ± 9.6 and 56.0 ± 6.5 ml 100 g−1 min−1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 ± 9.7 ml 100 g−1 min−1 ( p < 0.05 compared to 1 h ATP threshold value; all values are mean ± SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure. If the ischemic penumbra is considered to comprise the region in which cerebral protein synthesis is suppressed and energy state is preserved, it follows that the size of the penumbra decreases with the duration of ischemia.

Thresholds of focal cerebral ischemia in awake monkeys

1981 ◽  
Vol 54 (6) ◽  
pp. 773-782 ◽  
Author(s):  
Thomas H. Jones ◽  
Richard B. Morawetz ◽  
Robert M. Crowell ◽  
Frank W. Marcoux ◽  
Stuart J. FitzGibbon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neurological Function ◽  
Local Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print

✓ An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

scholarly journals Multiparametric Imaging of Blood Flow and Metabolism after Middle Cerebral Artery Occlusion in Cats

1985 ◽  
Vol 5 (1) ◽  
pp. 97-107 ◽  
Author(s):  
K.-A. Hossmann ◽  
G. Mies ◽  
W. Paschen ◽  
L. Csiba ◽  
W. Bodsch ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Glucose Utilization ◽  
Regional Blood Flow ◽  
Imaging Techniques ◽  
Atp Depletion ◽  
Poor Correlation ◽  
Left Middle Cerebral Artery

In anesthetized adult cats, acute stroke was produced by transorbital occlusion of the left middle cerebral artery. A battery of imaging techniques was used for simultaneous evaluation of regional blood flow, glucose utilization, protein synthesis, pH, and the regional tissue content of glucose, ATP, and potassium. The electrophysiological impact of stroke was monitored by EEG frequency analysis and recording of somatosensory evoked potentials. Two hours after vascular occlusion, a close correlation existed between the degree of electrophysiological changes and biochemical alterations, in particular with the extent of tissue acidosis, ATP depletion, decrease of tissue potassium content, and suppression of protein synthesis. However, there was only a poor correlation with blood flow and glucose utilization. Both of these exhibited a greatly inhomogeneous pattern with regions of reduced, normal, or increased rates. In areas remote from the infarct, the content of biochemical substrates was normal but blood flow was reduced globally by ∼50% and glucose utilization by ∼20%. An anatomically defined regional pattern of cerebral or cerebellar diaschisis was not observed. It is concluded that during the acute phase of stroke, imaging of blood flow and glucose utilization does not provide an accurate estimate of the actual functional or metabolic disturbance. For the clinical evaluation of the development or treatment of stroke, in consequence, alternative noninvasive techniques such as imaging of protein synthesis and/or pH may be more relevant.

scholarly journals Nimodipine Prevents Hyperglycemia-Induced Cerebral Acidosis in Middle Cerebral Artery Occluded Rats

1989 ◽  
Vol 9 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Leo Berger ◽  
Antoine M. Hakim
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Ischemia ◽  
Local Cerebral Blood Flow ◽  
Cerebral Tissue ◽  
Mca Occlusion ◽  
Double Label ◽  
Tissue Acidosis ◽  
Autoradiographic Technique

The effects of acute moderate hyperglycemia on local cerebral pH (LCpH) and local cerebral blood flow (LCBF) were studied in rats infused with glucose before middle cerebral artery (MCA) occlusion, and compared with findings in MCA occlusion alone. The effects of nimodipine infusion on LCBF and LCpH in MCA-occluded hyperglycemic rats were also studied. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique. Hyperglycemia was induced by an intraperitoneal injection of 2 g/kg D-glucose before MCA occlusion. Nimodipine-treated rats received the drug as an intravenous infusion of 0.5 μg/kg/min starting 15 min after occlusion, and ending at decapitation 4 h postocclusion. Cortical LCpH of five structures in the MCA territory of hyperglycemic rats varied between 6.64 ± 0.04 and 6.72 ± 0.02 (means ± SEM). These values were significantly lower than LCpH in the same ischemic structures in the control rats, which varied between 6.76 ± 0.04 and 6.82 ± 0.03 (p < 0.05 for four of five structures). Cortical LCpH of hyperglycemic nimodipine-treated rats ranged between 6.94 ± 0.02 and 7.05 ± 0.02, indicating significant elevations in LCpH (p < 0.001) compared with the untreated ischemic hyperglycemic animals. LCBF in the ischemic structures was not modified by hyperglycemia or nimodipine treatment. This suggests that nimodipine, by mechanisms other than improvement in blood flow, can prevent the enhanced cerebral tissue acidosis produced by hyperglycemia before incomplete focal ischemia.

scholarly journals Focal and Perifocal Changes in Tissue Energy State during Middle Cerebral Artery Occlusion in Normo- and Hyperglycemic Rats

1992 ◽  
Vol 12 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Jaroslava Folbergrová ◽  
Hajime Memezawa ◽  
Maj-Lis Smith ◽  
Bo K. Siesjö
Keyword(s):  
Energy Metabolism ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Energy State ◽  
Control Sample ◽  
Artery Occlusion ◽  
Cellular Energy ◽  
Mca Occlusion ◽  
Cerebral Artery Occlusion

The objective of the present study was to assess changes in cellular energy metabolism in focal and perifocal areas of a stroke lesion and to explore how these changes are modulated by preischemic hyperglycemia. A model for reversible occlusion of the middle cerebral artery (MCA) in rats was used to study changes in energy metabolism. Following MCA occlusion for 5, 15, or 30 min in normoglycemic rats, the tissue was frozen in situ, and samples from the lateral caudoputamen and from two neocortical areas were collected for metabolite analyses, together with a control sample from the contralateral, nonischemic hemisphere. Two other groups, subjected to 30 min of MCA occlusion, were made hyperglycemic by acute glucose infusion or by prior injection of streptozotocin. Enzymatic techniques were used for measurements of phosphocreatine, creatine, ATP, ADP, AMP, glycogen, glucose, pyruvate, and lactate. The neocortex of the contralateral, nonischemic hemisphere had labile metabolites that were similar to those measured in control animals. Ipsilateral neocortex bordering the focus, and thus constituting the “penumbra,” showed mild to moderate ischemic changes. In the “focus” (lateral caudoputamen plus the overlying neocortex), deterioration of energy state was rapid and relatively extensive (ATP content 20–40% of control). After 5 min of occlusion, no further deterioration of metabolic parameters was observed. Substrate levels were markedly reduced, and lactate content rose to ∼10 mM kg−1. In the animals with the most severe energy depletion, no additional accumulation of lactate occurred, suggesting substrate depletion. This was confirmed by the results obtained in the hyperglycemic subjects whose tissue lactate contents rose to ∼20 m M kg−1. However, the energy state of the focus was better preserved in both hyperglycemic groups as compared with the normoglycemic group. It has been shown, in this model, that relatively brief occlusion periods are required to induce infarction. The present results demonstrate that this can occur in spite of the absence of pronounced depletion of energy reserves. After 30 min of MCA occlusion, infarction developed in the lateral caudoputamen, but not in the neocortex. Since a similar perturbation in metabolic state was demonstrated here, other factors must contribute to the degree of tissue damage. The present results suggest that damage is exaggerated by hyperglycemia because it allows additional lactate to accumulate in the partially substrate-depleted tissue.

scholarly journals A Reproducible Model of Middle Cerebral Artery Occlusion in Mice: Hemodynamic, Biochemical, and Magnetic Resonance Imaging

1998 ◽  
Vol 18 (4) ◽  
pp. 367-375 ◽  
Author(s):  
Ryuji Hata ◽  
Günter Mies ◽  
Christoph Wiessner ◽  
Klaus Fritze ◽  
Daniel Hesselbarth ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Protein Synthesis ◽  
Magnetic Resonance ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Imaging Techniques ◽  
Resonance Imaging ◽  
Infarct Core ◽  
Triphenyltetrazolium Chloride ◽  
Mca Occlusion

A reproducible model of thread occlusion of the middle cerebral artery (MCA) was established in C57 Black/6J mice by matching the diameter of the thread to the weight of the animals. For this purpose, threads of different diameter (80 to 260 μm) were inserted into the MCA of animals of different weights (18 to 33 g), and the success of vascular occlusion was evaluated by imaging the ischemic territory on serial brain sections with carbon black. Successful occlusion of the MCA resulted in a linear relationship between body weight and thread diameter ( r = 0.46, P < 0.01), allowing precise selection of the appropriate thread size. Laser-Doppler measurements of CBF, neurological scoring, and 2,3,5-triphenyltetrazolium chloride staining confirmed that matching of animal weight and suture diameter produced consistent cerebral infarction. Three hours after MCA occlusion, imaging of ATP, tissue pH, and cerebral protein synthesis allowed differentiation between the central infarct core, in which ATP was depleted, and a peripheral penumbra with reduced protein synthesis and tissue acidosis but preserved ATP content. Perfusion deficits and ischemic tissue alterations could also be detected by perfusion- and diffusion-weighted magnetic resonance imaging, demonstrating the feasibility of dynamic evaluations of infarct evolution. The use of multiparametric imaging techniques in this improved MCA occlusion model opens the way for advanced pathophysiological studies of stroke in gene-manipulated animals.

scholarly journals Dynamics of Regional Brain Metabolism and Gene Expression After Middle Cerebral Artery Occlusion in Mice

2000 ◽  
Vol 20 (2) ◽  
pp. 306-315 ◽  
Author(s):  
Ryuji Hata ◽  
Keiichiro Maeda ◽  
Dirk Hermann ◽  
Günter Mies ◽  
Konstantin-Alexander Hossmann
Keyword(s):  
Protein Synthesis ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Imaging Techniques ◽  
Vascular Occlusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Final Size ◽  
Infarct Core ◽  
Hsp70 Mrna ◽  
Mca Occlusion

The evolution of brain infarcts during permanent occlusion of the middle cerebral artery (MCA) was studied in mice using multiparametric imaging techniques. Regional protein synthesis and the regional tissue content of ATP were measured on adjacent cryostat sections at increasing intervals after vascular occlusion ranging from 1 hour to 3 days. The observed changes were correlated with the expression of the mRNA of hsp70, c-fos, c-jun, and junB, as well as the distribution of DNA double-strand breaks visualized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL). One hour after MCA occlusion, the tissue volume with suppressed protein synthesis was distinctly larger than that in which ATP was depleted. With ongoing ischemia time, the ATP-depleted area gradually expanded and, within 1 day, merged with the region of suppressed protein synthesis. Expression of hsp70 mRNA occurred mainly in the penumbra (defined as the region of suppressed protein synthesis but preserved ATP), peaking at 3 hours after vascular occlusion. Expression of the immediate-early genes c-jun, c-fos, and junB increased both in the penumbra and the periinfarct normal tissue already at 1 hour after vascular occlusion, with slightly different regional and temporal patterns for each of these genes. DNA fragmentations were clearly confined to neurons; they appeared after 1 day in the infarct core (defined as the region of suppressed ATP) and never were detected in the penumbra. The late appearance of TUNEL after infarcts had reached their final size and the absence in the penumbra points against a major pathogenetic role of apoptosis. Permanent MCA occlusion in mice thus produces a gradually expanding infarct, the final size of which is heralded by the early inhibition of protein synthesis.

Effect of Thrombolysis on the Dynamics of Infarct Evolution After Clot Embolism of Middle Cerebral Artery in Mice

2000 ◽  
Vol 20 (10) ◽  
pp. 1483-1491 ◽  
Author(s):  
Takayuki Hara ◽  
Günter Mies ◽  
Konstantin-Alexander Hossmann
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Tissue Injury ◽  
Therapeutic Benefit ◽  
Additional Treatment ◽  
Atp Depletion ◽  
Control Group ◽  
Gradual Improvement

Reversible focal ischemia may lead to delayed tissue injury despite primary restoration of blood flow and metabolism. The authors investigated whether such delayed changes also occur after thrombolytic treatment of thromboembolic stroke. Clot embolism of the middle cerebral artery (MCA) was produced in C57/B16J mice by intracarotid injection of heterologous clots. One hour after embolism, one group was treated with intracarotid infusion of rt-PA (10 mg/kg). The untreated control group received an equal amount of vehicle. Just before onset of treatment and after 1, 3, 6, and 24 hours, animals were frozen in situ and cerebral blood flow (CBF), cerebral protein synthesis (CPS), ATP content, and DNA fragmentations (TUNEL) were imaged on cryostat sections using double tracer autoradiography, bioluminescence, and immunohistochemical techniques, respectively. In untreated animals (n = 20), CPS was suppressed in approximately 68% of hemispheric transsection at 1 hour after embolization. The ATP depleted area was smaller (approximately 58%), but between 6 and 24 hours it merged with that of CPS suppression. TUNEL-positive neurons became visible between 6 and 24 hours exclusively in regions with ATP depletion. rt-PA-induced thrombolysis (n = 20) led to the gradual improvement of blood flow. At 24 hours, ATP depletion was fully reversed and the CPS suppression area declined to approximately 16% of hemispheric transsection. Despite progressive metabolic recovery, large numbers of neurons became TUNEL-positive and animals died between 24 and 48 hours. Thrombolysis after clot embolism restores metabolic activity including protein synthesis, but the therapeutic benefit is limited by secondary injury that requires additional treatment to improve final outcome.

scholarly journals Doppler ultrasound in pregnancy – quality requirements of DEGUM and clinical application (part 2)

2021 ◽  
Author(s):  
Renaldo Faber ◽  
Kai-Sven Heling ◽  
Horst Steiner ◽  
Ulrich Gembruch
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Umbilical Artery ◽  
Prophylactic Treatment ◽  
Doppler Sonography ◽  
First Trimester ◽  
Ductus Venosus ◽  
Fetal Diagnosis

AbstractThis second part on Doppler sonography in prenatal medicine and obstetrics reviews its clinical applications. While this has not become the initially anticipated screening tool, it is used for the diagnosis and surveillance of a variety of fetal pathologies. For example, the sonography-based determination of uterine artery blood flow indices is an important parameter for the first trimester multimodal preeclampsia risk assessment, increasing accuracy and providing indication for the prophylactic treatment with aspirin. It also has significant implications for the diagnosis and surveillance of growth-restricted fetuses in the second and third trimesters through Doppler-sonographic analysis of umbilical artery, middle cerebral artery and ductus venosus. Here, especially the hemodynamics of the ductus venosus provides a critical criterium for birth management of severe, early-onset FGR before 34 + 0 weeks of gestation. Further, determination of maximum blood flow velocity of the middle cerebral artery is a central parameter in fetal diagnosis of anemia which has been significantly improved by this analysis. However, it is important to note that the mentioned improvements can only be achieved through highest methodological quality. Importantly, all these analyses are also applied to twins and higher order multiples. Here, for the differential diagnosis of specific complications such as TTTS, TAPS and TRAP, the application of Doppler sonography has become indispensable. To conclude, the successful application of Doppler sonography requires both exact methodology and precise pathophysiological interpretation of the data.

Effect of Ketanserin on Global Cerebral Blood Flow and Middle Cerebral Artery Flow Velocity

1995 ◽  
Vol 80 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Andreas Weyland ◽  
Heidrun Stephan ◽  
Frank Grune ◽  
Wolfgang Weyland ◽  
Hans Sonntag
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Middle Cerebral Artery ◽  
Flow Velocity ◽  
Cerebral Artery ◽  
Global Cerebral Blood Flow ◽  
Artery Flow
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