CO2 reactivity and heterogeneity of cerebral blood flow in ischemic, border zone, and normal cortex

1989 ◽  
Vol 257 (2) ◽  
pp. H473-H482 ◽  
Author(s):  
S. C. Jones ◽  
B. Bose ◽  
A. J. Furlan ◽  
H. T. Friel ◽  
K. A. Easley ◽  
...  

Regional arterial CO2 tension (PaCO2) reactivity of cerebral blood flow (CBF) and the effect of PaCO2 on the spatial and temporal heterogeneity of CBF were investigated by using autoradiographically determined CBF in the rat middle cerebral artery occlusion model after a 2-h period under pentobarbital anesthesia to clarify the relation between PaCO2 reactivity, CBF heterogeneity, and the temporal cycling of CBF. PaCO2 was adjusted to one of four levels. CBF was determined in four cortical areas and white matter using the tissue fractionation of [14C]iodoantipyrine [( 14C]IAP) in combination with vessel mapping using in vivo 4% thioflavine S. Specific PaCO2 reactivity and CBF were normal in the nonischemic cortex, normal, although slightly depressed, in the border zone far from the ischemic core area, and depressed in the border zone adjacent to the ischemic core area (P less than 0.001) and the ischemic core (P less than 0.001). In normocapnic and hypocapnic animals, CBF heterogeneity in the form of regularly spaced CBF columns perpendicular to the cortical surface was observed in the nonischemic hemisphere but was absent in the ischemic core area. In hypercapnic rats, flow columns were present in the ischemic core areas and border zones but were absent on the nonischemic side. There was a highly significant interaction (P less than 0.0001) in observer-determined heterogeneity grades between PaCO2 level and each of three areas, normal, border zone, and ischemic core. In normal cortex, comparison of the thioflavine S-stained vessels with the flow columns provided evidence supporting the concept of capillary recruitment and cycling as a mode of normal cerebral blood flow control. The presence of flow columns in severely ischemic areas in hypercapnic animals indicates that a short period of high PaCO2 transiently augments microregional flow and could enhance the delivery of a therapeutic agent to these microregions of the ischemic core. The regional analysis of PaCO2 reactivity suggests an index of future tissue viability.

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S488-S488
Author(s):  
Hwa Kyoung Shin ◽  
Phillip Jones ◽  
Andrew K Dunn ◽  
David A Boas ◽  
Michael A Moskowitz ◽  
...  

2007 ◽  
Vol 28 (5) ◽  
pp. 995-1008 ◽  
Author(s):  
Melissa M McClure ◽  
Art Riddle ◽  
Mario Manese ◽  
Ning Ling Luo ◽  
Dawn A Rorvik ◽  
...  

Periventricular white matter (PVWM) injury is the leading cause of neurologic disability in survivors of prematurity. To address the role of ischemia in PVWM and cerebral cortical injury, we hypothesized that immaturity of spatially distal vascular ‘end zones’ or ‘border zones’ predisposes PVWM to greater decreases in cerebral blood flow (CBF) than more proximal structures. We quantified regional CBF with fluorescently labeled microspheres in 0.65 gestation fetal sheep in histopathologically defined three-dimensional regions by post hoc digital dissection and coregistration algorithms. Basal flow in PVWM was significantly lower than in gyral white matter and cortex, but was equivalent in superficial, middle, and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) did not differ significantly during ischemia or reperfusion between PVWM, gyral white matter, or cortex. Moreover, CBF during ischemia-reperfusion was equivalent in three adjacent PVWM levels and was not consistent with the magnitude of severity of PVWM injury, defined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUPT nick end labeling) staining. However, the magnitude of ischemia was predicted by the severity of discrete cortical lesions. Hence, unlike cerebral cortex, unique CBF disturbances did not account for the distribution of PVWM injury. Previously defined cellular maturational factors, thus, appear to have a greater influence on PVWM vulnerability to ischemic injury than the presence of immature vascular boundary zones.


Stroke ◽  
2018 ◽  
Vol 49 (4) ◽  
pp. 924-930 ◽  
Author(s):  
Longting Lin ◽  
Andrew Bivard ◽  
Timothy Kleinig ◽  
Neil J. Spratt ◽  
Christopher R. Levi ◽  
...  

2001 ◽  
Vol 21 (3) ◽  
pp. 202-210 ◽  
Author(s):  
Yuji Kuge ◽  
Chiaki Yokota ◽  
Masafumi Tagaya ◽  
Yasuhiro Hasegawa ◽  
Akira Nishimura ◽  
...  

The authors recently developed a primate thromboembolic stroke model. To characterize the primate model, the authors determined serial changes in cerebral blood flow (CBF) and the relation between CBF and cerebral metabolic rate of glucose (CMRglc) using high-resolution positron emission tomography. Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot into the left internal carotid artery. Cerebral blood flow was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 24 hours after embolization. Lesion size and location 24 hours after embolization was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The results are summarized as follows: (1) 1 hour after embolization, CBF in the temporal cortex and the basal ganglia decreased to < 40% of the contralateral values. In these regions, regarded as an ischemic core, CBF decreased further with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated by being unstained with TTC were consistently observed in these regions. (2) In the parietal cortex and several regions surrounding the ischemic core, CBF was >40% of the contralateral values 1 hour after embolization and recovered gradually with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased compared with that in the contralateral regions, indicating an uncoupling of CBF and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron emission tomography investigations using this model will provide better understanding of the pathophysiology of thromboembolic stroke in humans.


1986 ◽  
Vol 6 (4) ◽  
pp. 414-424 ◽  
Author(s):  
Maiken Nedergaard ◽  
Albert Gjedde ◽  
Nils Henrik Diemer

Focal cerebral ischemia was induced in rats by occlusion of the middle cerebral artery. By a triple-tracer technique, cerebral glucose utilization, glucose content, and blood flow were simultaneously determined. Computer-assisted autoradiography revealed a core of dense ischemia in the lateral two-thirds of the striatum. A border zone of increased 2-deoxy-d-glucose (DG) uptake surrounded the ischemic insult in the acute stage. The lumped constant was increased only moderately in the border zone. Therefore, the enhanced DG uptake reflected increased glucose consumption. CBF was reduced to 20–30% in the cortical border, while minor depression and in some animals hyperemia were evident in the striate border. Six hours after the insult, the border zones of increased glucose consumption had disappeared in half the animals. In no animals examined after 20 h was glucose consumption enhanced. The study indicated a stable metabolic response to a reproducible focal insult. We conclude that continued enhancement of glucose consumption in marginally perfused areas indicates neuronal damage.


1976 ◽  
Vol 44 (2) ◽  
pp. 215-225 ◽  
Author(s):  
Francis W. Gamache ◽  
Ronald E. Myers ◽  
Esteban Monell

✓ The authors studied local cerebral blood flow in monkeys rendered hypotensive by infusion of a ganglionic blocking agent. Application of the 14C-antipyrine method demonstrated that the blood flow: 1) normally varies reproducibly from one structure to another within the brain; 2) appears at its lowest level in all structures during the early minutes of a rapid-onset hypotension; 3) maintains the same general rank order of blood flow rate during hypotension as was present during normotension; and 4) returns to supranormal levels immediately following the rapid restoration of blood pressure. The values for local cerebral blood flow remain close-to-normal in some animals and diminish significantly in others during late recovery from hypotension. The close-to-normal values accompany uncomplicated recoveries while the diminished values appear in those animals which became neurologically depressed. Areas of the brain considered predisposed to hypotensive injury did not exhibit depressions in blood flow rate during hypotension more markedly than did other brain areas. The present results are interpreted as strong evidence against the “border zone” hypothesis.


1982 ◽  
Vol 52 (2) ◽  
pp. 376-387 ◽  
Author(s):  
J. E. Koerner ◽  
R. L. Terjung

The influence of physical training on coronary collateral circulation following acute ligation of the left coronary artery was determined in pentobarbital-anesthetized rats. Coronary blood flows were determined with 15-microns microspheres during a wide range of perfusion pressures and during adenosine infusion. The demarcation between normal and ischemic tissue was achieved using nitroblue tetrazolium strain and thioflavin S fluorescence. Contractile performance was not altered by training, with the exception of a lower left ventricular end-diastolic pressure when afterload was elevated. Blood flow to and the size of the central ischemic zone were not influenced by training. However, in border zones, where collateral dependent flow is expected to be most pronounced, blood flow as a percent of normal was increased (16%, P less than 0.02) in trained animals. This increased was abolished by coronary vasodilation with adenosine. These results indicate that training caused a limited increase in collateral blood flow to the border zone. Further, tissue reactivity to adenosine following short periods of ischemia is normal in trained rats but decreased in border (11%) and ischemic (21%, P less than 0.05) zones in sedentary rats. Whether his small increase in blood flow to the border tissue, along with a retained capacity for dilatation, could lead to an improved salvage of tissue remains to be evaluated.


2015 ◽  
Vol 35 (4) ◽  
pp. 699-705 ◽  
Author(s):  
Manouchehr S Vafaee ◽  
Albert Gjedde ◽  
Nasrin Imamirad ◽  
Kim Vang ◽  
Mallar M Chakravarty ◽  
...  

Acute nicotine administration stimulates [14C]deoxyglucose trapping in thalamus and other regions of rat brain, but acute effects of nicotine and smoking on energy metabolism have rarely been investigated in human brain by positron emission tomography (PET). We obtained quantitative PET measurements of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) in 12 smokers who had refrained from smoking overnight, and in a historical group of nonsmokers, testing the prediction that overnight abstinence results in widespread, coupled reductions of CBF and CMRO2. At the end of the abstention period, global grey-matter CBF and CMRO2 were both reduced by 17% relative to nonsmokers. At 15 minutes after renewed smoking, global CBF had increased insignificantly, while global CMRO2 had increased by 11%. Regional analysis showed that CMRO2 had increased in the left putamen and thalamus, and in right posterior cortical regions at this time. At 60 and 105 minutes after smoking resumption, CBF had increased by 8% and CMRO2 had increased by 11–12%. Thus, we find substantial and global impairment of CBF/CMRO2 in abstaining smokers, and acute restoration by resumption of smoking. The reduced CBF and CMRO2 during acute abstention may mediate the cognitive changes described in chronic smokers.


2021 ◽  
pp. neurintsurg-2021-018239
Author(s):  
Gregory A Christoforidis ◽  
Niloufar Saadat ◽  
Mira Liu ◽  
Yong Ik Jeong ◽  
Steven Roth ◽  
...  

BackgroundSanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO).MethodsUnder an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO.ResultsMean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276).ConclusionPreliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.


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