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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In the past, physicians viewed ischemic injury as an irreversible event. Modern science has shown that this view is incorrect and that ischemic neuronal damage is an ongoing, active process that might be amenable to various therapies. Figure 2 illustrates some of the possible sites where these therapies might be active. Pending evidence of their effectiveness, cerebral protection can best be achieved by maintaining adequate CPP and CBF during periods when patients are at risk for cerebral ischemia, restoring perfusion after ischemia occurs, and optimizing the metabolic milieu of the ischemic penumbra.
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PMID:Current concepts in cerebral protection. 813 75

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

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

Induction of hsp70 heat shock protein (HSP70) and hsp70 mRNA was examined using adjacent sections in the same rat brain following permanent middle cerebral artery (MCA) occlusions, hsp70 mRNA was induced within 4 h of MCA occlusion and persisted for at least 24 h. Cellular resolution autoradiographs suggested that hsp70 mRNA was induced primarily in neurons in the periphery of ischemia both outside and inside of the infarction, with small amounts of hsp70 mRNA being induced in the core of the infarction. HSP70 protein was localized in neurons outside the infarction and in endothelial cells within the infarction at 24 h but not at 4 h following permanent MCA occlusions. It is proposed that the penumbra, one of the areas that can be rescued by pharmacological agents, can be defined anatomically as the volume of tissue outside the area of infarction in which HSP70 protein is expressed primarily in neurons.
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PMID:Induction of heat shock hsp70 mRNA and HSP70 kDa protein in neurons in the 'penumbra' following focal cerebral ischemia in the rat. 837 89

Leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) are the 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid (AA). They constrict blood vessels and enhance vascular permeability inducing vasogenic edema that may hurt the ischemic penumbra after cerebral ischemia and reperfusion. Nordihydroguaiaretic acid (NDGA) is known as the most potent inhibitor of 5-lipoxygenase in different tissues. Furthermore, it has considerable inhibitory activity against cyclooxygenase. In this study, after developing a global ischemic model in the rat, the levels of LTC4 and PGE2 in the forebrain were measured, following different reperfusion periods after 10 min ischemia including 8 rats for each reperfused group. Sham operations were performed for each corresponding control group (n = 8). AA metabolites were then correlated with neuropathological findings. In the combined reperfused groups both metabolites increased significantly when compared with 10 min, ischemic group (P < 0.05). In the 8 min reperfused group, PGE2 and LTC4 increased significantly compared with each corresponding control group (P < 0.005). These mediators also increased to high levels compared with the 4 min reperfused group (P < 0.05, P < 0.005). PGE2 and LTC4 were reduced significantly at the 15th and 60th min of reperfusion compared with the 8 min reperfused group (P < 0.05, P < 0.005). NDGA (0.1 mg/kg) reduced both metabolites in the 8 min reperfused group significantly (P < 0.05). Brain cortex specimens were taken for light and electromicroscopical investigations. No significant differences were noted between the structural changes in the 4, 8 and 15 min of reperfusion and NDGA administered groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of nordihydroguaiaretic acid on leukotriene C4 and prostaglandin E2 production following different reperfusion periods in rat brain after forebrain ischemia correlated with morphological changes. 841 14

Induction of the 70-kDa heat shock protein (HSP70) was demonstrated immunocytochemically in adult rats 4 h to 7 days following temporary middle cerebral artery (MCA) occlusions lasting 30, 60, or 90 min. Maximal HSP70 induction occurred approximately 24 h following ischemia. Thirty minutes of ischemia induced HSP70 in neurons throughout the cortex in the MCA distribution, whereas 90 min of ischemia induced HSP70 in neurons in the penumbra. HSP70 protein was induced in endothelial cells in infarcted neocortex following 60-90 min of MCA occlusion, and HSP70 was induced in endothelial cells in infarcted regions of lateral striatum following 30-90 min of MCA occlusion. hsp70 mRNA was induced in the MCA distribution in cortex and to a lesser extent in striatum at 2 h to 3 days following 60 min of ischemia. It is proposed that brief ischemia induces hsp70 mRNA and HSP70 protein in the cells most vulnerable to ischemia--the neurons. HSP70 protein is not induced in most neurons and glia following 60-90 min of ischemia in areas destined to infarct, whereas it is induced in vascular endothelial cells.
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PMID:Induction of 70-kDa heat shock protein and hsp70 mRNA following transient focal cerebral ischemia in the rat. 841 99

Impairment of energy metabolism is the fundamental mechanism leading to cell death in ischemia. Using the middle cerebral artery (MCA) occlusion model in cats, we studied the effect of Duxil (almitrine and raubasine combination), which was given either before and after or only after MCA occlusion, on ischemia in terms of neurological function and histological changes. Neurological function was assessed consecutively for 7 days after MCA occlusion using a categorical rating scale in 18 cats. Neurological function was significantly improved in treated animals than in non-treated controls regarding to the motor and sensory function, walking, posture and stepping reflex. Animals were killed on the 8th day and histological changes were examined by light and electron microscopies. Significant improvement in the morphological scores based on the light-microscopy changes were found in animals treated with Duxil compared to non-treated ones. Under the electron microscopy, the protective effects of Duxil were characterized by retaining glycogen and mitochondria. Morphological improvement was associated with the recovery of neurological function and especially profound in penumbra areas of MCA infarction. These results suggest that Duxil has a protective effect against ischemic damage induced by occlusion of MCA in cats.
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PMID:Neurologic and histologic evaluation of almitrine+raubasine (Duxil) in middle cerebral artery occlusion in cats. 845 73

Changes occurring in the extracellular fluid (ECF) concentration of energy-related metabolites were investigated in a well-characterized model of compression trauma to the spinal cord. Microdialysis probes were inserted into exposed grey matter of the dorsal horn at the level of Th 7-8, and perfused with mock cerebrospinal fluid. The trauma was produced 2 hours later by compression of the cord with a 9-, 35-, or 50-g load for 5 min. Microdialysis samples (10-minute fractions) were collected for another 2 hours following decompression. The trauma was associated with an accumulation of lactate, inosine, and hypoxanthine, and an increase in the lactate/pyruvate ratio in the ECF, indicating a profound disturbance in energy metabolism. These changes were related to the severity of spinal cord injury as well as to the spinal cord blood flow (SCBF) reductions and neurological deteriorations previously determined. Following decompression, all ECF metabolites normalized within 20-40 min after mild (9 g) to moderate (35 g) trauma. After severe trauma (50 g), resulting in complete ischemia during compression, followed by irreversible paraplegia, there was a partial recovery of ECF inosine and hypoxanthine, whereas the increase in lactate and the lactate/pyruvate ratio persisted. The results suggest that penumbra conditions prevail during the early posttraumatic period when the degree of trauma results in severe neurological deterioration and that ECF lactate levels in the spinal cord is a sensitive indicator of secondary ischemia after compression injury.
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PMID:Time course of energy perturbation after compression trauma to the spinal cord: an experimental study in the rat using microdialysis. 848 49


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