Experimental ischemic stroke: a review.

Summary: Local CMRgl (LCMRgl) and metabolite levels were measured in the same tissue samples fol lowing 4 h of recirculation after 1 h of occlusion of the middle cerebral artery in the caL The rate of glucose utilization was calculated using direct measurement of tissue deoxyglucose-6-phosphate and using a "lumped" constant corrected in each sample for alterations in tissue glucose, Increased LCMRgl (compared with that in sham operated animals) occurred in regions with only minor alterations in levels of lactate and phosphocreatine, By contrast, LCMRgl was markedly depressed in regions Glucose is the principal substrate for energy me tabolism in brain, Measurement of the local CMRgl (LCMRgl) using the radiolabeled glucose analogue [ l4 C]2-deoxyglucose ([ l4 C]2DG) has been a valuable method for evaluating functional activity of brain tissue (Sokoloff, 1981;Greenberg and Reivich, 1983). Among numerous applications of this tech nique, there have been several reports showing a broad spectrum of changes in LCMRgl in animal studies of ischemia, ranging from marked inhibition to pronounced activation (Ginsberg et ai., 1977;Diemer and Siemkowicz, 1980; Welsh et ai., 1980a; Pulsinelli et ai., 1982; Choki et aI., 1983). In addi tion, we recently examined the flow-metabolism couple during the recovery period after cerebral ischemia in the cat (Tanaka et aI., 1985) and found Abbreviations used: 2DO, 2-deoxyglucose; 2DO-6-P, 2-deoxy glucose-6-phosphate; LC, lumped constant; LCMRgl, local CMRgI; MCA, middle cerebral artery; Pc, phosphorylation con stant. 502with major changes in lactate and high-energy phos phates, Interestingly, tissue levels of glucose and un phosphorylated deoxyglucose were abnormally elevated in regions with profound energy failure, These results in dicate an inhibition of glucose utilization in regions dam aged by ischemia, despite the persistent elevation of tissue lactate, Increased glucose metabolism at 4 h post ischemia was detected only in areas with minor anaerobic alteration of metabolite levels, Key Words: Brain glu cose-Deoxyglucose-Energy metabolism-Glucose metabolism-Ischemia-Regional metabolites, that the preservation of a normal flow/metabolism ratio was a critical factor in maintaining tissue via bility.In spite of such important contributions to the study of the metabolic function of brain tissue after ischemia, the [ l4 C]2DG method does not distinguish between aerobic and anaerobic utilization of glu cose and does not provide direct information about the energy state of the tissue. One of the aims of the present study was thus to investigate the rela tionship between the tissue concentration of var ious metabolites (ATP, phosphocreatine, lactate, and glucose) and LCMRgl as determined by the [ 14 C]2DG method during the recirculation period following ischemia. Although measurement of re gional glucose metabolism in human brain has be come feasible utilizing positron emission tomog raphy (Phelps et aI., 1979; Reivich et aI., 1979 Reivich et aI., , 1982, the imaging of regional tissue ...

Section: Discussion Lc For the 2dg Modelmentioning

confidence: 99%

Regional Alterations in Glucose Consumption and Metabolite Levels during Postischemic Recovery in Cat Brain

Tanaka

Welsh

Greenberg³

et al. 1985

“…Occlusion of the MCA produces complete ischemia in only a very limited area of the brain (Welch and Barkley, 1986); in these regions the lack of glucose leads to cell death within a short period of time after isch emia (Garcia, 1984). However, due to the collateral circulation of the MCA territory, there is a penum bra of reduced flow around the ischemic core (As trup et aI., 1981).…”

Section: Discussionmentioning

confidence: 99%

Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [¹⁴C]Deoxyglucose Technique

Greenberg¹,

Hamar²,

Welsh

et al. 1992

Summary: We measured the parameter A, which is the ratio of the distribution spaces of2-deoxY-D-glucose (DG) and glucose in the brain, in a model of focal cerebral ischemia in the cat. A is the parameter in the lumped constant of the [14C]DG technique most susceptible to changes in ischemia. Cats were subjected to occlusion of the middle cerebral artery for a period of 2 h. During the last 60 min of occlusion, [14C]DG was infused in a pro grammed fashion so as to obtain a stable arterial blood [14C]DG concentration. The brain was funnel-frozen to preserve tissue metabolites and the frozen brain was sam pled regionally (4 to 7-mg samples) for local concentra tions of glucose, ATP, phosphocreatine (PCr), and lac-

“…For example, the critical period of experimental middle cerebral artery (MCA) occlusion for the production of infarction has variously been re ported to range from 1 to 4 h (Tamura et al, 1980;Crowell et aI., 1981;De Girolami et aI., 1984;Weinstein et al, 1986). Occlusion of the MCA in large animals produces an ischemic insult whose degree and spatial extent tend to be variable (Garcia, 1984). Rodent models of MCA occlusion are advantageous in that the ischemia is more con sistent, and auto radiographic measurements of CBF and glucose metabolism may be easily per formed without prohibitive expense (Tamura et al, 198 1;Tyson et aI., 1984).…”

Section: Discussionmentioning

confidence: 99%

“…, 1981;Marcoux et aI. , 1982;Garcia, 1984). The extent of infarction or ischemic cell damage produced by I h of MCA occlusion in the cat or monkey is reported to be small, consisting of scattered foci of necrosis or ischemic cell damage (Marcoux et aI.…”

Section: Discussionmentioning

confidence: 99%

Photothrombotic Occlusion of Rat Middle Cerebral Artery: Histopathological and Hemodynamic Sequelae of Acute Recanalization

Nakayama

Dietrich

Watson

et al. 1988

The histopathological and hemodynamic consequences of photochemically induced middle cerebral artery (MCA) thrombosis and recanalization were studied in the rat. Recanalization of the thrombosed MCA segment was achieved by the topical application of nimodipine at 1 h following photochemically induced occlusion. Pathological consequences of permanent and temporary occlusion were compared by morphometric procedures 7 days following thrombus formation. Rats with permanent thrombosis exhibited consistent infarction of both striatum and cortex. MCA recanalization at 1 h was associated with a significant reduction in total infarct volume. In recanalized rats, small cortical infarcts, confined to the peripheral MCA territory, were observed in only three of six rats. In contrast, a mixed pattern of infarction and ischemic cell damage was documented throughout the striatum in all rats. Local CBF (ICBF), measured autoradiographically, was significantly reduced in the MCA territory following 1 h of MCA occlusion, especially within the striatum. At 1 h after recanalization, lCBF recovered within the previously ischemic brain regions to >50% of control. Perfusion deficits were detected by carbon black infusion within focal areas of the striatum following reperfusion. Thus, cortical neurons appear to tolerate 1 h of MCA occlusion in this model. In contrast, reperfusion following 1 h of photochemically induced MCA occlusion gives rise to selective injury to the striatum.