Episodes Of Brain Ischemia Research Articles

LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer's Disease with 2-Year Survival.

Explaining changes at the gene level that occur during neurodegeneration in the CA3 area is crucial from the point of view of memory impairment and the development of post-ischemic dementia. An ischemic model of Alzheimer's disease was used to evaluate changes in the expression of genes related to amyloid transport in the CA3 region of the hippocampus after 10 min of brain ischemia with survival of 2, 7 and 30 days and 12, 18 and 24 months. The quantitative reverse transcriptase PCR assay revealed that the expression of the LRP1 and RAGE genes involved in amyloid transport was dysregulated from 2 days to 24 months post-ischemia in the CA3 area of the hippocampus. LRP1 gene expression 2 and 7 days after ischemia was below control values. However, its expression from day 30 to 24 months, survival after an ischemic episode was above control values. RAGE gene expression 2 days after ischemia was below control values, reaching a maximum increase 7 and 30 days post-ischemia. Then, after 12, 18 and 24 months, it was again below the control values. The data indicate that in the CA3 area of the hippocampus, an episode of brain ischemia causes the increased expression of the RAGE gene for 7-30 days during the acute phase and that of LRP1 from 1 to 24 months after ischemia during the chronic stage. In other words, in the early post-ischemic stage, the expression of the gene that transport amyloid to the brain increases (7-30 days). Conversely, in the late post-ischemic stage, amyloid scavenging/cleaning gene activity increases, reducing and/or preventing further neuronal damage or facilitating the healing of damaged sites. This is how the new phenomenon of pyramidal neuronal damage in the CA3 area after ischemia is defined. In summary, post-ischemic modification of the LRP1 and RAGE genes is useful in the study of the ischemic pathways and molecular factors involved in the development of Alzheimer's disease.

MANAGEMENT OF GIANT MIDDLE CEREBRAL ARTERY ANEURYSMS WITH INCORPORATED BRANCHES

Our goal was to assess the long-term anatomic and clinical outcomes in patients with giant middle cerebral artery (MCA) aneurysms treated by endovascular coil embolization alone or in combination with cerebral revascularization. One hundred twenty-six patients with giant intracranial aneurysms were endovascularly treated at the University of California, Los Angeles, between 1990 and 2007. Of these, 9 patients had partially thrombosed MCA aneurysms with incorporated branches. Five patients presented with symptoms of mass effect, 3 had seizures, 2 had episodes of brain ischemia, and 1 presented with acute subarachnoid hemorrhage. Three wide-neck saccular aneurysms were almost completely coil occluded, leaving only small neck remnants that were intended to preserve the patency of incorporated MCA branches. The other 6 fusiform aneurysms were effectively treated by superficial temporal artery-MCA or occipital artery-MCA bypass, followed by complete coil occlusion of these aneurysms. Immediate angiograms and mid- or long-term neuroradiological imaging follow-up examinations revealed complete obliteration or near-complete occlusion (90%-99%) of the aneurysms in all 9 patients. Seven patients had a favorable long-term clinical outcome, and 1 patient died as a result of unrelated congestive heart failure. One patient required emergent surgical aneurysm thrombectomy because of inadvertent coil occlusion of the frontal opercular artery, which was not protected by the bypass, and the patient subsequently sustained a moderate neurological disability. Giant MCA aneurysms with branch incorporations and other unfavorable features such as intraluminal thrombus, mural calcification, and fusiform configuration can be effectively treated with a team approach, using coil embolization after protective surgical bypass. When aneurysms with MCA branches incorporated into the neck rather than the dome are treated by endovascular techniques alone, long-term angiographic follow-up is necessary to assess and further treat any significant remnant.

A 70-Year-Old Man With a Transient Ischemic Attack

Mr V, a man with severe coronary, aortic, and peripheral artery disease, had an episode of brain ischemia caused by severe preocclusive carotid artery disease in the neck. The major treatment options for his symptomatic carotid artery disease are optimizing medical treatment, carotid endarterectomy, and carotid artery stenting. Selection of treatment must take into consideration his severe symptomatic coronary artery disease as well as Mr V's concerns about surgery. Carotid endarterectomy presents a risk of myocardial infarction unless his coronary disease is treated effectively before surgery. Carotid stenting is problematic because the severity of the preocclusive arterial narrowing makes passing a protective device beyond the stenosis difficult without first performing potentially hazardous angioplasty. Optimizing medical treatment may be the best option for his severe systemic atherosclerosis. Treatment decisions in complex patients like Mr V require weighing the particular risks and benefits of available options, and the patient's own wishes and fears. These decisions, in this and other complex patients, often cannot be directly informed by results from randomized trials.

Protein Aggregation and Proteasome Dysfunction After Brain Ischemia

Protein unfolding and aggregation are dominant early pathogenic events in neurons after brain ischemia. This study used a transient cerebral ischemia model to investigate whether overproduction of unfolded proteins after brain ischemia is a consequence of proteasome dysfunction. Proteasome peptidase activity and proteasome subcellular redistribution and assembly were studied by peptidase activity assay, Western blot analysis, and size-exclusion chromatography. Proteasome peptidase activity, as determined with the peptide substrate succinyl-LLVY-7-amino-4-methylcoumarin, was moderately decreased, and the 26S proteasome was disassembled during the early period of reperfusion after transient brain ischemia. Furthermore, the proteasome subunits, particularly the 19S components, were deposited into the protein aggregate-containing fraction after an episode of transient cerebral ischemia. These results clearly demonstrate that after an episode of brain ischemia, proteasomes are disassembled and aggregated and thus fail to function normally. Deposition of proteasomes into protein aggregates may also indicate that proteasomes attempt to degrade ubiquitin-conjugated proteins (ubiproteins) overproduced after brain ischemia. However, ubiproteins are too numerous to be degraded and trap some of the proteasomes into their aggregates after brain ischemia.

Monitorage intracérébral d'un patient ayant un vasospasme

Delayed neurological deficit occurs among 30% of patients after aneurysmal subarachnoid haemorrhage, mainly related to cerebral vasospasm. The early detection of cerebral ischemia remains problematic. Conventional cerebral monitoring (as intracranial pressure and cerebral perfusion pressure) appears to be insufficient, because cerebral ischemia may occur without elevated intracranial pressure. Global cerebral monitoring as venous jugular oxygen saturation are useful for regional monitoring. Local monitoring as oxygen tissue partial pressure (PtiO2) and microdialysis are sensible for brain ischemia detection, but may also ignore episodes occurring in non-monitored brain area. For the detection of most episodes of brain ischemia, several monitoring system should be use performing a multimodal intracerebral monitoring. Brain microdialysis and oxygen tissue partial pressure are promising monitoring system.

The PROGRESS Trial: Preventing Strokes by Lowering Blood Pressure in Patients With Cerebral Ischemia

A blood pressure is an unhealthy thing to have, to a large extent. Prospective population-based observational studies have shown a continuous, positive relationship between blood pressure and the risk of stroke or other major vascular events. There is no “safe” level of blood pressure below which the risk ceases to diminish. The association is even stronger than one might surmise from casual measurements, because of regression to the mean on subsequent readings. After appropriate correction, prolonged differences in usual diastolic blood pressure of 5, 7.5, and 10 mm Hg are respectively associated with at least 34%, 46%, and 56% relative risk reduction of stroke.1,2 The effectiveness of antihypertensive treatment in the primary prevention of stroke leaves no doubt about the causality of the relationship: systematic reviews show that a diastolic blood pressure reduction of 5 to 6 mm Hg results in a large decrease in stroke rate, in the order of 35% to 50%.3,4 Until now, the question remained whether blood pressure reduction was equally beneficial in patients after a transient ischemic attack (TIA) or a stroke. Theoretically, irreparable damage might already have occurred at the time of the first manifestation of cerebrovascular disease. A slightly crude analogy is that abstaining from cigarettes greatly improves prognosis in the general population but not much in patients with bronchial carcinoma. Systematic reviews showed equivocal benefit of blood pressure reduction in 4 clinical trials in which an episode of brain ischemia was the qualifying event.5 In subsets of patients with previous stroke from trials of antihypertensive treatment in general, the evidence was somewhat more robust, but not for normotensive patients.6 Therefore the recently published PROGRESS trial can be regarded as an impressive undertaking.7 The target population consisted mostly of patients with ischemic stroke, brain TIA, or transient monocular …

Improvement of cerebrovascular reserve capacity by EC-IC arterial bypass surgery in patients with ICA occlusion and hemodynamic cerebral ischemia

Since the negative results of the international Bypass Study, extracranial-intracranial (EC-IC) bypass surgery is infrequently employed in the treatment of patients with cerebral ischemia. Newly acquired evidence concerning the pathophysiology of cerebral ischemia, however, has facilitated the identification of a small subgroup of patients with "hemodynamic" cerebral ischemia. Characteristically, these patients demonstrate severely impaired cerebrovascular reserve capacity due to occlusive disease and insufficient collateral blood supply. Over an 8-year period, 28 patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had recurring episodes of focal cerebral ischemia due to unilateral internal carotid artery occlusion. Computerized tomography (CT) scans either were normal or showed evidence of border zone infarction. The cerebrovascular reserve capacity was studied using 133Xe single-photon emission CT and acetazolamide challenge and was found to be significantly impaired in all patients. Based on these criteria, superficial temporal artery-middle cerebral artery anastomosis was performed to augment collateral flow to the ischemic hemispheres. Two patients died from myocardial infarction, one 4 days and the other 2 months postoperatively. One patient died from massive brain infarction and another suffered a postoperative stroke with incomplete recovery, resulting in a major morbidity and mortality rate of 14%. Minor morbidity included one patient with a subdural hematoma who subsequently recovered completely. The postoperative course was uneventful in 23 patients (82%). Over a mean follow-up period of almost 3 years, no patient had another episode of brain ischemia. Bypass patency was confirmed by postoperative angiography in 26 patients. Follow-up studies of cerebral blood flow (CBF) and cerebrovascular reserve capacity showed significant improvement of the latter while the resting CBF was essentially unchanged. In view of these findings, the authors conclude that EC-IC bypass surgery constitutes appropriate therapy for a subgroup of patients with recurrent focal cerebral ischemia, defined using the strict selection criteria employed in this study.