Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia

1989 ◽  
Vol 70 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Toshihiko Kuroiwa ◽  
Makoto Shibutani ◽  
Riki Okeda
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Reactive Hyperemia ◽  
Diffusion Method ◽  
Left Middle Cerebral Artery ◽  
Content Type ◽  
Bbb Opening ◽  
Fine Print

✓ The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

Thresholds of focal cerebral ischemia in awake monkeys

1981 ◽  
Vol 54 (6) ◽  
pp. 773-782 ◽  
Author(s):  
Thomas H. Jones ◽  
Richard B. Morawetz ◽  
Robert M. Crowell ◽  
Frank W. Marcoux ◽  
Stuart J. FitzGibbon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neurological Function ◽  
Local Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print

✓ An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

Spinal cord stimulation reducing infarct volume in a model of focal cerebral ischemia in rats

2003 ◽  
Vol 99 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Oren Sagher ◽  
Dah-Luen Huang ◽  
Richard F. Keep
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Spinal Cord Stimulation ◽  
Focal Cerebral Ischemia ◽  
Doppler Flowmetry ◽  
Content Type ◽  
Baseline Values ◽  
Fine Print

Object. The authors previously showed that spinal cord stimulation (SCS) increases cerebral blood flow in rats, indicating that this technique may be useful in the treatment of focal cerebral ischemia. In the present study, the neuroprotective potential of SCS in the setting of middle cerebral artery occlusion (MCAO) was investigated. Methods. The authors induced permanent, focal cerebral ischemia by using either suture-induced occlusion or direct division of the MCA in Sprague—Dawley rats. Electrical stimulation of the cervical spinal cord was performed during cerebral ischemia. Cerebral blood flow was assessed using both laser Doppler flowmetry (LDF) and quantitative radiotracer analysis. Stroke volumes were analyzed after 6 hours of ischemia. Spinal cord stimulation resulted in a 52.7 ± 13.3% increase in LDF values (nine animals). Following MCAO, LDF values decreased by 64.1 ± 3.6% from baseline values (10 animals). Spinal cord stimulation subsequently increased LDF values to 30.9 ± 13.5% below original baseline values. These findings were corroborated using radiotracer studies. Spinal cord stimulation in the setting of transcranial MCAO significantly reduced stroke volumes as well (from 203 ± 33 mm3 [control] to 32 ± 8 mm3 [MCAO plus SCS], seven animals in each group, p < 0.001). Similarly, after suture-induced MCAO, SCS reduced stroke volumes (from 307 ± 29 mm3 [control] to 78 ± 22 mm3 [MCAO plus SCS], 10 animals in each group, p < 0.001). Conclusions. A strategy of performing SCS for the prevention of critical ischemia is feasible and may have the potential for the treatment and prevention of stroke.

Microregional blood flow changes in experimental cerebral ischemia

1971 ◽  
Vol 35 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Y. Lucas Yamamoto ◽  
Kathryne M. Phillips ◽  
Charles P. Hodge ◽  
William Feindel
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Fluorescein Angiography ◽  
Focal Cerebral Ischemia ◽  
Gamma Activity ◽  
Collateral Flow ◽  
Silicon Detectors ◽  
Content Type ◽  
Perfusion Flow ◽  
The Brain

✓ A branch of the middle cerebral artery on the convexity of the dog brain was occluded to produce an area of focal cerebral ischemia which could then be defined by fluorescein angiography of the brain. Repeated fluorescein angiography and measurement of microregional cerebral blood flow by xenon133 injected into the carotid artery and monitored by miniature lithium-drifted silicon detectors for gamma activity demonstrated that the ischemic zone was reduced in size by better collateral flow when the animals were allowed to breathe 5% carbon dioxide and 95% oxygen. Conversely, hyperventilation reducing the pCO2 made the ischemic zone larger by reducing collateral flow. No evidence was found to indicate that hypercapnia preferentially deprived the ischemic zone of perfusion flow. Retrograde collateral flow in the surface arteries appeared effective in terms of microcirculatory perfusion.

The therapeutic value of nimodipine in experimental focal cerebral ischemia

1987 ◽  
Vol 67 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Isabelle M. Germano ◽  
Henry M. Bartkowski ◽  
Mary E. Cassel ◽  
Lawrence H. Pitts
Keyword(s):  
Cerebral Ischemia ◽  
Mechanism Of Action ◽  
Neurological Outcome ◽  
Focal Cerebral Ischemia ◽  
Ischemic Insult ◽  
Double Blind ◽  
Content Type ◽  
Therapeutic Value ◽  
Fine Print ◽  
Neuropathological Evaluation

✓ Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1,4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p < 0.001, p < 0.01, p < 0.05, respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p < 0.01, p < 0.01, p < 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the “penumbra” of the ischemic area.

scholarly journals Nimodipine Pretreatment Improves Cerebral Blood Flow and Reduces Brain Edema in Conscious Rats Subjected to Focal Cerebral Ischemia

1990 ◽  
Vol 10 (6) ◽  
pp. 903-913 ◽  
Author(s):  
Michael Jacewicz ◽  
Steve Brint ◽  
Jody Tanabe ◽  
Xing-Je Wang ◽  
William A. Pulsinelli
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Polyethylene Glycol 400 ◽  
Conscious Rats ◽  
Ischemic Core ◽  
Cortical Ischemia ◽  
Vascular Steal ◽  
Common Carotid Arteries

The effect of nimodipine pretreatment on CBF and brain edema was studied in conscious rats subjected to 2.5 h of focal cortical ischemia. An infusion of nimodipine (2 μg/kg/min i.v.) or its vehicle, polyethylene glycol 400, was begun 2 h before the ischemic interval and was continued throughout the survival period. Under brief halothane anesthesia, the animals' right middle cerebral and common carotid arteries were permanently occluded, and 2.5 h later, they underwent a quantitative CBF study ([14C]iodoantipyrine autoradiography followed by Quantimet 970 image analysis). Nimodipine treatment improved blood flow to the middle cerebral artery territory without evidence of a “vascular steal” and reduced the volume of the ischemic core (cortex with CBF of < 25 ml/100 g/min) and accompanying edema by ∼50% when compared with controls (p = 0.006 and 0.0004, respectively). Mild hypotension induced by nimodipine did not aggravate the ischemic insult. The ischemic core volumes, however, were 50–75% smaller than the 24-h infarct volumes generated in a similar paradigm that demonstrated 20–30% infarct reduction with continuous nimodipine treatment. These results suggest that nimodipine pretreatment attenuates the severity of early focal cerebral ischemia, but that with persistent ischemia, cortex surrounding the ischemic core undergoes progressive infarction and the early benefit of nimodipine treatment is only partly preserved.

Delayed treatment with magnesium: reduction of brain infarction and improvement of electrophysiological recovery following transient focal cerebral ischemia in rats

2005 ◽  
Vol 102 (6) ◽  
pp. 1085-1093 ◽  
Author(s):  
E-Jian Lee ◽  
Ming-Yang Lee ◽  
Guan-Liang Chang ◽  
Li-Hsuan Chen ◽  
Yu-Ling Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Content Type ◽  
Delayed Treatment ◽  
Cerebral Ischemia Reperfusion ◽  
Fine Print

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion. Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died. Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively. Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.

Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia

1992 ◽  
Vol 77 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Bruce I. Tranmer ◽  
Ted S. Keller ◽  
Glenn W. Kindt ◽  
David Archer
Keyword(s):  
Cardiac Output ◽  
Cerebral Ischemia ◽  
Blood Volume ◽  
Volume Expansion ◽  
Focal Cerebral Ischemia ◽  
Brain Regions ◽  
Ischemic Brain ◽  
Content Type ◽  
Blood Volume Expansion ◽  
Fine Print

✓ Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% ± 92%, mean ± standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% ± 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p < 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.

Impaired microvascular filling after focal cerebral ischemia in monkeys

1972 ◽  
Vol 36 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Robert M. Crowell ◽  
Yngve Olsson
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Cerebrovascular Diseases ◽  
Subcortical Structures ◽  
Content Type ◽  
Microsurgical Technique ◽  
Small Vessels ◽  
Mca Occlusion ◽  
Vascular Channels ◽  
Fine Print

✓ Impairment of microvascular filling was demonstrated in relation to focal cerebral ischemia in the monkey. Temporary or sustained middle cerebral artery (MCA) clipping was achieved with a microsurgical technique. Animals were sacrificed by perfusion with a carbon black suspension. Brains were fixed in formalin, and the extent of microvascular carbon filling was estimated grossly and microscopically. In most animals, MCA occlusion of 2 hours to 7 days produced diminished filling in small vessels in the MCA territory of supply. The impairment of filling was most pronounced in the deep subcortical structures but also affected the cortex in some animals. Temporary and sustained occlusion of equal duration produced roughly equivalent areas of abnormal filling. The impairment of vascular filling tended to be more extensive with increasing duration of occlusion. Hypotension during MCA occlusion caused almost total non-filling of the microvasculature in the entire MCA territory. Impaired filling of vascular channels may play a role in the pathogenesis of some clinical cerebrovascular diseases.

Effect of nimodipine on intracellular brain pH, cortical blood flow, and EEG in experimental focal cerebral ischemia

1986 ◽  
Vol 64 (4) ◽  
pp. 617-626 ◽  
Author(s):  
Fredric B. Meyer ◽  
Robert E. Anderson ◽  
Tony L. Yaksh ◽  
Thoralf M. Sundt
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Cortical Blood Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Brain Ph ◽  
Major Branch

✓ Intracellular brain pH, cortical blood flow, and electroencephalograms (EEG's) were recorded in severely and moderately ischemic regions in 10 control and 10 nimodipine-treated rabbits prior to and following major branch occlusion of the middle cerebral artery (MCA). Preocclusion cortical blood flow was 51 ml/100 gm/min and intracellular brain pH was 7.01 in both the control and the treated animals. After MCA occlusion, the severely ischemic regions in the control group showed initial and 4-hour postocclusion flows of 12.7 and 5.2 ml/100 gm/min with a brain pH of 6.64 and 6.08, respectively. In animals given nimodipine after MCA occlusion, blood flow increased from 10.5 to 18.8 ml/100 gm/min, with an associated elevation in intracellular brain pH from 6.57 to 6.91. Comparable findings were observed in areas of moderate ischemia. Improvements in cortical blood flow, intracellular brain pH, and EEG attenuations produced by nimodipine were all statistically significant. Inspection of the cortex revealed reversal of cortical pallor and small-vessel spasm following treatment with nimodipine. It is hypothesized that nimodipine exerts its effects through reversal of ischemia-induced secondary vasoconstriction, and that this drug may be an important adjunctive treatment for patients with focal cerebral ischemia.

Pathophysiology and treatment of focal cerebral ischemia

1992 ◽  
Vol 77 (2) ◽  
pp. 169-184 ◽  
Author(s):  
Bo K. Siesjö
Keyword(s):  
Cerebral Ischemia ◽  
Calcium Homeostasis ◽  
Calcium Binding ◽  
Focal Cerebral Ischemia ◽  
Ion Homeostasis ◽  
Atp Depletion ◽  
Content Type ◽  
Cellular Calcium ◽  
Intracellular Ca ◽  
Fine Print

✓ This article examines the pathophysiology of lesions caused by focal cerebral ischemia. Ischemia due to middle cerebral artery occlusion encompasses a densely ischemic focus and a less densely ischemic penumbral zone. Cells in the focus are usually doomed unless reperfusion is quickly instituted. In contrast, although the penumbra contains cells “at risk.” these may remain viable for at least 4 to 8 hours. Cells in the penumbra may be salvaged by reperfusion or by drugs that prevent an extension of the infarction into the penumbral zone. Factors responsible for such an extension probably include acidosis, edema, K+/Ca++ transients, and inhibition of protein synthesis. Central to any discussion of the pathophysiology of ischemic lesions is energy depletion. This is because failure to maintain cellular adenosine triphosphate (ATP) levels leads to degradation of macromolecules of key importance to membrane and cytoskeletal integrity, to loss of ion homeostasis, involving cellular accumulation of Ca++, Na+, and Cl−, with osmotically obligated water, and to production of metabolic acids with a resulting decrease in intra- and extracellular pH. In all probability, loss of cellular calcium homeostasis plays an important role in the pathogenesis of ischemic cell damage. The resulting rise in the free cytosolic intracellular calcium concentration (Ca++) depends on both the loss of calcium pump function (due to ATP depletion), and the rise in membrane permeability to calcium. In ischemia, calcium influx occurs via multiple pathways. Some of the most important routes depend on activation of receptors by glutamate and associated excitatory amino acids released from depolarized presynaptic endings. However, ischemia also interferes with the intracellular sequestration and binding of calcium, thereby contributing to the rise in intracellular Ca++. A second key event in the ischemic tissue is activation of anaerobic glucolysis. The main reason for this activation is inhibition of mitochondrial metabolism by lack of oxygen; however, other factors probably contribute. For example, there is a complex interplay between loss of cellular calcium homeostasis and acidosis. On the one hand, a rise in intracellular Ca++ is apt to cause mitochondrial accumulation of calcium. This must interfere with ATP production and enhance anaerobic glucolysis. On the other hand, acidosis must interfere with calcium binding, thereby contributing to the rise in intracellular Ca++.

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