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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular homeostatic adaptation to cerebral ischemia is complex and contains changes in receptor mediated gene expression and signaling pathways. The proteins of the immediate early genes c-Fos and c-Jun are thought to be involved in coupling neuronal excitation to target gene expression, due to formation of heterodimers and binding to the AP1 promotor region. We used an in vitro model to compare ischemia induced c-Fos and c-Jun expression in rat neuronal cell cultures and nerve growth factor (NGF) differentiated PC 12 cells. Since activation of glutamate receptors is known to mediate ischemic injury we determined the effect of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 on c-Fos and c-Jun expression in both cell culture systems during ischemia. Neuron rich cultures and NGF differentiated PC 12 cells were exposed to sublethal in vitro ischemia using an hypoxic chamber flushed with argon/CO2 (95 %/5%). C-Fos and c-Jun mRNA expression was analyzed by competitive reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as internal standard. One hour of in vitro ischemia significantly increased c-Fos and c-Jun mRNA levels in both cell culture systems. In neuron rich cultures a 10-fold (c-Fos) and 7-fold (c-Jun) mRNA increase was observed. The mRNA rise was less pronounced in PC 12 cells (5.5-fold and 2-fold) for c-Fos and c-Jun, respectively. The addition of MK 801 significantly reduced the expression of c-Fos and c-Jun mRNA in neuronal cultures, whereas no effect was detectable in PC 12 cells. Since MK 801 failed to reduce the c-Fos and c-Jun expression in NGF differentiated PC 12 cells different signaling pathways may initiate c-Fos and c-Jun expression in both cell culture systems.
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PMID:MK 801 attenuates c-Fos and c-Jun expression after in vitro ischemia in rat neuronal cell cultures but not in PC 12 cells. 1239 13

To investigate the expression of the HO-1 gene in PC12 cells in hypoxic environment and gain further insight to the role of HO-1 in cerebral ischemia, PC12 cells were exposed to hypoxia environment (95% N2, 5% CO2) for 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h respectively. The level of HO-1 mRNA was examined by reverse transcriptase polymerase chain reaction (RT-PCR); the volume of COHb in the media were measured spectrophotometrically and the cGMP concentration of PC12 cell extracts was determined by radioimmunoassay. We found that after exposure to hypoxia for 1 h, 4 h, 8 h, 12 h, 24 h, HO-1 mRNA increased by 3%, 4%, 17%, 31% 36% as compared with that in control group respectively (P < 0.01 or P < 0.05); the COHb increased by 12%, 29%, 59%, 88%, 94% as compared with that in control group respectively (P < 0.01 or P < 0.05), and the cGMP concentration were 2.2, 3.4, 5.2, 8.1, 10.9-fold as that of the control group (P < 0.01). We are led to conclude that hypoxia induced the expression of HO-1 gene, the production of endogenous CO, and the concentration of cGMP was elevated as well.
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PMID:Induction of the expression of heme oxygenase gene in PC12 cells by hypoxia. 1267 63

Clinical data suggest that cerebral blood flow (CBF) can be abnormally low within the first four to eight hours after severe head injury (SHI). An aggressive hyperventilation can additionally worsen CBF and provoke cerebral ischemia. Therefore an accurate PCO2 monitoring in SHI patients (pts) is necessary. PetCO2 failed to reflect PaCO2 in SHI pts treated in neurosurgical ICU. Up to now, the validity of PetCO2 monitoring in estimating PaCO2 during an acute posttraumatic craniotomy has not been studied. Forty five adult SHI pts operated on because of an acute intracranial posttraumatic haematoma within 8 hours after head trauma entered the study. The standard anaesthetic protocol included N2O/O2, fentanyl and pancuronium bromide anaesthesia, and mechanical ventilation with respiratory rate 10 divided by 12 bpm and tidal volume in mL = body weight (kg) x 10 - 100. After obtaining a stable PetCO2 arterial blood sample was taken for PaCO2 measurement and P(a-et)CO2 = PaCO2 - PetCO2 was calculated. P(a-et)CO2 ranged -9 divided by 20 mm Hg (5 +/- 6; mean +/- SD). P(a-et)CO2 between 2 mm Hg and 6 mm Hg was found in 17 (38%) patients only. A negative P(a-et)CO2 was stated in 20% of patients. No relationships between P(a-et)CO2 and pts age and mean arterial pressure were found. P(a-et)CO2 was higher in normocapneic pts than in hyperventilated ones and tended to decrease with an increase in heart rate. We can conclude that during an acute craniotomy in SHI pts, PetCO2 does not reflect accurately PaCO2 and the monitoring of adequacy of ventilation should be based on repeated or continuous measurements of an arterial PCO2.
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PMID:Arterial to end-tidal carbon dioxide difference during craniotomy in severely head-injured patients. 1281 73

It has been shown that the main problem of treating patients with cerebral ischemia using minimal excessive pressures is the choice of the optimum therapeutic dose. We propose a new method of treatment for cerebral vascular disorders with an application for minimum high pressure doses (< 1.1 ata with oxygen a air mixture). The aim of the present report is to summarize clinical results of this method and to estimate the mechanisms of its action. The main feature of the method described (barotherapy) is to bring external and cell respiration and recovery of oxygen autoregulation of cell respiration to normal values in patients with increased CO2 inner production. The administration of antioxidants transporting electrons on mitochondrial respiratory chain significantly improves the clinical outcome after barotherapy and leads to stabilization of lipid peroxidation.
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PMID:[Barotherapy in cerebrovascular diseases]. 1283 May 31

The excitatory amino acid glutamate is a potent vasodilator in the central nervous system. Glutamate-induced vasodilation is mediated primarily by N-methyl-D-aspartate (NMDA) and AMPA/kainate (KAIN) receptors. We have now tested whether two metabolites of the kynurenine pathway of tryptophan degradation acting at the NMDA receptor, the antagonist kynurenic acid (KYNA) and the agonist quinolinic acid (QUIN), are capable of modulating the dilation of pial arterioles. The closed cranial window technique was used, and changes in vessel diameter ( approximately 100 microm) were analyzed in anesthetized newborn piglets. Topical application of NMDA (10(-4) M) or KAIN (5 x 10(-5) M) resulted in marked vasodilation (44 +/- 5% and 39 +/- 4%, respectively). Neither KYNA nor QUIN (both at 10(-5) to 10(-3) M) affected the vessel diameter when applied alone. Co-application of KYNA dose-dependently reduced the vasodilation caused by 10(-4) M NMDA and also attenuated the KAIN-induced response. Ten minutes of global cerebral ischemia did not modify the interaction between KAIN and KYNA. In contrast, KYNA did not affect vasodilation to hypercapnia, elicited by the inhalation of 10% CO2. Moreover, endogenous levels of KYNA and QUIN in the cerebral cortex, hippocampus and thalamus were found to be essentially unchanged during the early reperfusion period (0.5-2 h) following an episode of cerebral ischemia. Our data are relevant for the use of drugs that target the kynurenine pathway for therapeutic interventions in cerebrovascular diseases.
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PMID:Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs. 1638 84

The specificity of jugular bulb saturation (SjO2) and arteriovenous oxygen difference (AVDO2) to detect global cerebral ischemia remains controversial. An absolute increase in the arteriovenous difference of carbon dioxide tension (AVDpCO2) and, more specifically, the estimated respiratory quotient (eRQ = AVDpCO2/AVDO2) may indicate anaerobic CO2 production. We compared these variables with SjO2 to predict global cerebral ischemia. We selected 36 patients from a cohort of 69 consecutive patients suffering from severe traumatic brain injury. All patients had jugular bulb sampling within 6 hours after injury. Brain death at 48 hours was used as a surrogate index of irreversible ischemia to build a receiver operating characteristics (ROC) curve analysis. The mean (+/- standard deviation) eRQ in the 13 patients who died early (3.7 +/- 3.2 mmHg/ml/dl) was higher than the survivors (1.78 +/- 0.45 mmHg/ml/dl, P = 0.03). There was no differences in SjO2 between groups. The area under the ROC curves for eRQ, but not that of AVDpCO2, was greater (P = 0.04) than that of SjO2. The eRQ, more than AVDpCO2, appears to be a potentially more informative index of global cerebral ischemia than SjO2.
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PMID:Estimated cerebral respiratory quotient and arteriovenous differences of CO2 in the ultra early detection of global ischemia in severe head injury. 1646 23

The reliable and reproducible creation of an animal model of focal cerebral ischemia is not easily accomplished. Using a transortibal approach, we showed that occlusion of the posterior cerebral artery (PCA), middle cerebral artery (MCA), and the contralateral anterior cerebral artery (ACA) created a large cortical and subcortical stroke in the non-human primate (NHP). Subsequently, we created the same stroke endovascularly in the NHP. Using the endovascular stroke model in the NHP, we measured brain temperature with thermocouples and cerebral blood flow (CBF) by stable xenon CT in one NHP, and CMRO2 and CBF by positron emission tomography (PET) in another NHP. Two female non-human primates (M. mulatta) weighing 7.0 and 8.0 kg, respectively, were studied under fentanyl-diazepam anesthesia with continuous monitoring of arterial blood pressure, rectal temperature, and end-tidal CO2 with intermittent blood gas measurements. Using an endovascular approach, the PCA (P2), MCA (M1), and the ICA at the bifurcation and contralateral ACA produced a large hemispheric stroke. In the right ischemic hemisphere, temperatures increased by 2 degrees C-3 degrees C. PET measurement of CBF and CMRO2 showed that CMRO2 increased in the region of the ischemic stroke. We found that both hyperthermia and hypermetabolism occur in acute stroke.
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PMID:Hyperthermia and hypermetabolism in focal cerebral ischemia. 1659 38

After the demonstration that spinal cord stimulation (SCS) can improve peripheral blood flow it was Hosobuchi ('86) who first studied the effect of SCS on cerebral blood flow (CBF) in human beings. Our group found that SCS can produce either an increase of CBF or a reduction or no effect. In patients studied with both SPECT technique and TCD, the sign of the induced variations, when present in both, was the same. Cervical stimulation produces more frequently an increase in CBF (61% of cervical stimulations). Our experimental studies confirm that SCS and CO2 interact with the mechanism of regulation of CBF in a competitive way and produce a reversible functional sympathectomy. Further experimental reports suggest that SCS 1) drastically prevents cerebral infarction progression in cats; 2) improves clinical symptoms of patients in persistent vegetative states; 3) suppress headache attacks in migraneous patients; 4) significantly reduces ischemic brain oedema in rats. Following these clinical and experimental observations, Hosobuchi first used cervical SCS for the treatment of cerebral ischemia in man ('91). More recently we confirmed the therapeutic effect of SCS on ischemic stroke in humans, experimental brain injury and cerebral vasospasm in rabbits.
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PMID:Spinal cord stimulation and cerebral haemodynamics. 1737 Jul 75

Hosobuchi first studied the effect of spinal cord stimulation (SCS) on cerebral blood flow (CBF) in human beings along with the demonstration that SCS can improve peripheral blood flow. Following these clinical and experimental observations Hosobuchi first used cervical SCS for the treatment of cerebral ischemia in man. Further experimental reports suggested so far that SCS 1) drastically prevents cerebral infarction progression along with a reduction in infarct volume in cats; 2) improves clinical symptoms of patients in persistent vegetative states; 3) suppress headache attacks in migraneous patients; 4) significantly reduces ischemic brain oedema in rats; 5) increase locoregional blood flow in high grade brain tumors. The authors found that SCS can produce either an increase of CBF or a reduction or no effect. In patients studied with both SPECT technique and transcranial Doppler (TCD) the sign of the induced variations, when present in both, as the same. Cervical stimulation produces more frequently an increase in CBF (61% of cervical stimulations). The authors' experimental studies confirm that SCS 1) interacts with CO2 with the mechanism of regulation of CBF in a competitive way and produce a reversible functional sympathectomy; 2) produces similar flowmetric changes in the brain as well as in the eyes; 3) can improve both clinical and haemodynamic ischemic stroke in humans; 4) prevents hemodynamic deterioration in the experimental combined ischemic and traumatic brain injury; 5) prevents experimental early vasospasm.
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PMID:Neuromodulation of cerebral blood flow by spinal cord electrical stimulation: the role of the Italian school and state of art. 1850 Feb 17

Gender differences, sex steroid effects, and sex-specific candidate therapeutics in ischemic stroke have been studied in rodents but not in nonhuman primates. In this feasibility study (n = 3 per group), we developed a model of transient focal cerebral ischemia in adult male and female rhesus macaques that consistently includes white matter injury. The animals also were used to determine whether gender-linked differences in histopathologic outcomes could be evaluated in this model in future, larger preclinical trials. Histologic brain pathology was evaluated at 4 d after 90 min of reversible occlusion of the middle cerebral artery (MCA). MCA occlusion was accomplished by using a transorbital approach and temporary placement of an aneurysm clip. Male and female rhesus macaques 7 to 11 y of age were studied. Baseline and intraischemic blood glucose, systolic blood pressure, heart rate, oxygen saturation, end-tidal CO2, and rectal temperatures were not different among groups. The variability in injury volume was comparable to that observed in human focal cerebrovascular ischemia and in other nonhuman primate models using proximal MCA occlusion. In this small sample, the volume of injury was not different between male and female subjects, but observed variability was higher in female caudate nucleus, putamen, and hemisphere. This report is the first to compare cerebral ischemic outcomes in female and male rhesus macaques. The female rhesus macaque ischemic stroke model could be used after rodent studies to provide preclinical data for clinical trials in women.
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PMID:Can gender differences be evaluated in a rhesus macaque (Macaca mulatta) model of focal cerebral ischemia? 1914 16


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