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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied whether administration of nitric oxide (NO) donors reduces the ischemic damage resulting from middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats (SHRs). In halothane-anesthetized and ventilated SHRs, the MCA was occluded. CBF was monitored using a laser-Doppler flowmeter. Three to five minutes after MCA occlusion, the NO donors sodium nitroprusside (SNP; 3 mg/kg/h) or 3-morpholino-sydnonimine (SIN 1; 1.5-6 mg/kg/h) were administered into the carotid artery for 60 min. As a control, the effect of papaverine (3.6 mg/kg/h), a vasodilator that acts independently of NO, was also studied. The hypotension evoked by these agents was counteracted by intravenous infusion of phenylephrine. At the end of the infusion, rats were allowed to recover. Stroke size was determined 24 h later in thionin-stained sections. In sham occluded rats, SNP (n = 5), SIN 1 (n = 5), and papaverine (n = 5) produced comparable increases in CBF (p > 0.05 from vehicle). After MCA occlusion, SNP (n = 5) and SIN 1 (n = 5), but not papaverine (n = 5), enhanced the recovery of CBF (p < 0.05 from vehicle) and reduced the size of the infarct by 28 +/- 12 and 32 +/- 7%, respectively (mean +/- SD; p < 0.05 from vehicle). To determine whether NO donors could act by inhibiting platelet aggregation, we studied the effect of SNP on collagen-induced platelet aggregation. Intracarotid administration of SNP (3 mg/kg/h for 60 min) did not affect platelet aggregation to collagen, suggesting that the protective effect of NO donors was not due to inhibition of platelet function. We conclude that NO donors increase CBF to the ischemic territory and reduce the tissue damage resulting from focal ischemia. The protective effect may result from an increase in CBF to the ischemic territory, probably the ischemic penumbra. These findings suggest that NO donors may represent a new therapeutic strategy for the management of acute stroke.
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PMID:Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia. 811 18

Testing vasoreactivity with CO2 or Diamox is a common diagnostic procedure for the study of haemodynamics in stroke patients. CO2 reactivity (CO2R) was tested in 5 baboons six hours after permanent occlusion of the left middle cerebral artery (MCA) in order to attain new insights into interpretation of vasoreactivity tests. Using the microsphere method, cerebral blood flow (CBF) was determined in the various vascular territories as well as in the centre of the ischemia, the penumbra and the remaining MCA-tissue. CBF decreased significantly in the affected MCA in all animals and in addition in the contralateral cerebellum in one animal (p < 0.05). In addition, the left anterior cerebral artery (ACA) demonstrated a similar decrease. During hypercapnia CBF increased in all areas with the exception of the left, occluded MCA territory. Thus CO2 enhanced the difference between ischaemic and non-ischaemic tissue (i.e., tissue with diaschisis). Mean CO2 R was 3.37 ml/100 g/min/mmHg in the right MCA, 0.16 in the left. While the left ACA demonstrated a decreased perfusion during normocapnia in a similar range to the MCA territory, only CO2R was able to identify precisely the territory of the occluded vessel. CO2 R was zero or negative in the ischaemic core, close to zero in the penumbra and profoundly decreased in the remaining MCA tissue. The overall CO2 R of the MCA was almost zero, suggesting vasoparalysis in response to hypercapnia in the core and penumbra and exhausted CO2 R even in non-infarcted, non-penumbral tissue. One animal displayed a negative CO2 R equivalent to an intracerebral steal-phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CO2 reactivity in the ischaemic core, penumbra, and normal tissue 6 hours after acute MCA-occlusion in primates. 812 41

The term ischemic penumbra, originally applied to brain tissue perfused at values between the functional and morphologic thresholds, has recently been extended to characterize ischemically affected but still viable tissue with uncertain chances for infarction or recovery. Results have accumulated supporting the concept of the ischemic penumbra as a dynamic process of impaired perfusion and metabolism eventually propagating with time from the center of ischemia to the neighboring tissue. As mediators and modulators of this process, waves of depolarization, extracellular increases in excitatory amino acids, activation of Ca++ channels, induction of immediate early genes and expression of heat-shock proteins, among others, have been discussed. The contribution of the various electrophysiologic and biochemical/molecular events to the complex cascade, eventually leading to neuronal damage, is still controversial. The demonstration of viable (penumbra) tissue by positron emission tomography up to several hours after ischemic stroke renders the rationale for therapeutic interventions. A short therapeutic window of a few hours is relevant for re-establishment of perfusion; the time-dependent propagation of the ischemic penumbra suggests an extended period for effective intervention with biochemical/molecular processes.
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PMID:The ischemic penumbra. 817 71

A comparison of the long-term outcome after surgical and nonsurgical treatment of hypertensive putaminal hemorrhage was performed in Japan over the last 15 years to determine the appropriate role of surgery. The overall results show a poor response to surgical treatment, but neurosurgeons also know that hematoma evacuation may bring about a dramatic result in some cases. In addition, experimental studies have shown that hematoma evacuation improves neuronal function at the penumbra. The discrepancy between the results of this study and the neurosurgeon's clinical impression is probably a reflection of the following. In the past, the decision to operate was determined mainly by the location of the hemorrhage as determined by computed tomography and/or magnetic resonance imaging. However, this method of deciding surgical indications is probably not correct. We are trying to change the method of determining the surgical indications from morphological to physiological criteria as follows: All patients are initially treated with hyperbaric oxygen, and those who show improvement of their symptoms are clearly indicated for surgery. If the somatosensory evoked potential or auditory brain stem response shows an improvement after administration of mannitol or glycerol, this is also an indication that surgery should be performed.
Stroke 1993 Dec
PMID:New approaches in the treatment of hypertensive intracerebral hemorrhage. 824 29

Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral metabolic standpoint, exposure to isoflurane at concentration of 2 MAC is credited with providing the same potential for protection as high dose barbiturate (isoelectric EEG). A possible major difference between barbiturates and isoflurane is the modest cerebral vasodilation induced by the latter while barbiturates are associated with decreased CBF. This suggests that in focal ischemia isoflurane may elicit an intracerebral steal. 3) Calcium entry blockers. Some calcium entry blockers with the distinctive feature of acting preferably on cerebral as opposed to systemic vascular smooth muscles may exert beneficial effects during or after brain ischemia. Two such drugs which have shown promise are nimodipine and lidoflazine. In animal and human studies nimodipine has been reported to improve the neurologic outcome of both the cerebral vasospasm and the postischemic hypoperfusion state.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cerebral protection]. 827 62

Cerebral infarction is the result of cerebrovascular insufficiency and itself creates complex changes in cerebral hemodynamics. To allow recognition of patterns of change in regional cerebral blood flow (r-CBF) caused by cerebral infarction, the authors present an atlas of Tc-99m hexamethylpropyleneamine oxime (Tc-99m HMPAO) SPECT brain scan sections for a variety of strokes demonstrating typical vascular territorial involvements and evolution of morphologic and r-CBF change. Sections from MRI or CT are shown with SPECT images of the stroke lesion for comparison of the complementary information provided by regional cerebroperfusion and by morphology. Examples of SPECT during acute, subacute, and chronic stages of stroke are provided. To illustrate the temporal evolution of stroke and accompanying changes in the "stroke penumbra," case examples of acute tissue necrosis, luxury perfusion, ischemia, and diaschisis are presented. Methods for semiquantitative analysis of morphologic versus r-CBF defect size after acute stroke are described. How brain SPECT scans conducted during Diamox initiated cerebrovascular stress tests can complement the information obtained from baseline studies and assist in the interpretation of r-CBF abnormalities is also demonstrated.
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PMID:Regional cerebral blood flow changes in stroke imaged by Tc-99m HMPAO SPECT with corresponding anatomic image comparison. 829 29

Magnetic source imaging (MSI) is a new, noninvasive technique for defining the relationship between brain function and structure on a patient-to-patient basis. It achieves this by combining detailed neurophysiological data derived from magnetoencephalography with high-quality neuroanatomical data derived via magnetic resonance imaging. By the use of mathematical models, the spatial locations of those neurons that generate neuromagnetic signals of interest are estimated and subsequently marked on spatially aligned magnetic resonance images. There are three prominent types of clinical MSI examinations. These are: 1) functional mapping examinations in which sensory and motor functions are localized; 2) examinations of interictal epileptiform activity; and 3) examinations of abnormal low-frequency magnetic activity, which has been found to be present in a wide range of pathophysiological conditions. Functional mapping provides useful information regarding the relationship between the cortical representation of eloquent function and the location of pathological lesions that may be surgically resectable. This application is of particular utility in cases of intracortical masses that distort and obscure the local neuroanatomy. By defining the primary sites of interictal epileptiform activity, MSI examinations are useful in the surgical planning for the implantation of depth electrodes and the planning of partial lobectomies. Abnormal low-frequency magnetic activity appears to be a neurophysiological correlate of ischemic penumbra associated with stroke, neoplasms, and vascular malformations. Abnormal low-frequency magnetic activity has also been found to be present in several other conditions, including head trauma and psychiatric dysfunction, although the exact pathophysiological mechanisms are presently unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Magnetic source imaging: a review of the Magnes system of biomagnetic technologies incorporated. 836 47

The efficacy of GM1 ganglioside treatment in stroke was studied in a permanent middle cerebral artery occlusion model in the rat. A dose-dependent attenuation of infarct size at 24 hr was documented with the maximum effective dose halving the volume of the experimental stroke. Delayed administration at 5 min, but not 15 min, after vessel occlusion was as effective as preocclusion drug administration. Morphologic sparing was confined to the cortical penumbra; no protection in the ischemic core was found. Morphologically salvaged cortex was also metabolically preserved as demonstrated by quantitative measurement of glucose utilization. In vivo microdialysis demonstrated an attenuation of ischemic-induced glutamate release in the cortex with GM1 administration but no effect was found in the caudate. Hypotension did not occur even with doubling of the maximally effective dose of GM1. Accordingly, GM1 may be a safe and effective treatment for stroke.
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PMID:GM1 ganglioside treatment of focal ischemia: a dose-response and microdialysis study. 847 9

Detailed assessment of stroke is essential to distinguish haemorrhage from infarction, to establish the vascular territory affected and to identify patients with carotid stenosis or cardio-embolic disease. Computed tomography scanning should be routinely undertaken. Duplex Doppler sonography and echocardiography should be readily available but used selectively. Hypertension should not be treated early after ischaemic stroke. Issues requiring research include the optimal time to institute treatment, the degree to which blood pressure should be lowered in the presence of carotid stenosis and the value of antihypertensive treatment in normotensive survivors of stroke. Anticoagulation should be more widely applied in the prevention of stroke in patients with atrial fibrillation. Thrombolysis for acute ischaemic stroke has potential benefits and risks. It should be used only within randomised clinical trials, some of which may soon report. Endogenous glutamate causes excitotoxic damage after cerebral ischaemia. Many pharmacological approaches to restrict neuronal loss within the ischaemic penumbra are now in clinical trials. Physicians managing hypertension should take a lead in researching blood pressure management and neuroprotective strategies after acute stroke, and in directing other preventive measures such as anticoagulation for atrial fibrillation.
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PMID:Diagnosis and therapeutic aspects of stroke. 853 24

In the last few years considerable evidence has been seen making it clear that although focal neurological deficiency (or ischaemic stroke) develops in parallel with intracranial arterial occlusion, the irreversible damage neurons suffer (i e necrosis) in many parts of the ischaemic territory is delayed by several hours. After an occlusion of the middle cerebral artery, such a lapse is particularly evident in the region of the cerebral cortex, an area which could be considered as the most peripheral region of the ischaemic territory, also known as 'penumbra'. This article sets out to review the secondary events in time-dependent studies which show that many of the consequences of intracranial artery occlusion may be totally or partly reversible by reopening the artery 60 minutes after. The right middle cerebral artery (MCA) of some two hundred adult Wistar rats was blocked up by inserting a nylon monofilament through the outer carotid artery. In some of the animals such occlusion was resolved by removing the filament minutes or hours later whereas in others light from the MCA remained occluded until the end of the experiment seven days later. Many histological and histochemical analyses were performed as well as microscopic preparation for each subject to obtain information concerning the movement of circulating leucocytes and of platelets, the integrity of capillaries as opposed to a circulating macromolecule (mw: 43 kd), the development of neuronal necrosis and the relationship between neurological deficiency and the level of histological damage. Once the MCA was blocked, both neuronal necrosis and leukocyte movement followed a somewhat parallel course. A large number of necrotic neurons appeared in the next twelve hours, coinciding with the time most intravascular leukocytes (neutrophiles) take in making themselves visible around the area affected by the blocked artery. In any case, prior to the development of neuronal necrosis and of leucotaxis, significant abnormalities appear affecting the perivascular astrocytes and capillary endothelial cells. The structural changes in these cells, and especially tumefaction, are what cause important abnormalities in microvascular integrity appearing several hours before neuronal necrosis. To recap: a) despite the fact that leucocyte migration and progressive neuronal necrosis follow a parallel course in time, the casual relationship between these two physiopathological phenomena is still not firmly established: b) the structural changes affecting vascular endothelial cells and astrocytes could fulfill a primordial role in possible neuronal necrosis that in the context of an experimental infarct is not produced until six hours after arterial blockage; c) microvascular deterioration may be reversible by reopening the blockage if this is carried out at most 60 minutes afterwards. This point would suggest that selective treatment of ischaemic stroke patients using thrombotic agents or angioplasty could have beneficial effects.
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PMID:[Early reperfusion as a rationale from of therapy in ischemic stroke]. 855 95


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