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ABSTRACT: Hypoglycemia can cause brain dysfunction, brain injury, and death. The present study seeks to broaden current information regarding mechanisms of hypoglycemic brain injury by investigating a novel etiology. The cat's high resistance to brain injury from hypoglycemia suggested that additional influences such as respiratory depression might play a facilitating role. Three groups of cats were exposed to fasting and insulin-induced hypoglycemia (HG; n = 6), euglycemic respiratory depression (RD; n = 5), and combined hypoglycemic respiratory depression (HG/RD; n = 10). The HG animals were maintained at <1.5 mmol (mean 1 mmol) serum glucose concentration for 2 to 6.6 hours. The respiratory depression was associated with PaO2 and PaCO2 values of approximately 50 mm Hg for 1 hour and of approximately 35 and approximately 75 mm Hg, respectively, for the second hour. Magnetic resonance diffusion-weighted imaging estimated brain energy state before, during, and after hypoglycemia. The hypoglycemic respiratory depression exposures were terminated either to euglycemia (n = 4) or to hyperglycemia (n = 6). Brain injury was assessed after 5 to 7 days of survival. Cats exposed to hypoglycemia alone maintained unchanged diffusion coefficients; that is, they lacked evidence of brain energy failure and all six remained brain-intact. Only 1 of 5 euglycemic RD but 10 of 10 HG/RD cats developed brain damage (HG and RD vs. HG/RD, P < 0.01). This difference in brain injury rates suggests injury potentiation by hypoglycemia and respiratory depression acting together. Three injury patterns emerged, including activation of microglia, selective neuronal necrosis, and laminar cortical necrosis. Widespread activation of microglia suggesting damage to neuronal cell processes affected all damaged brains. Selective neuronal necrosis affecting the cerebral cortex, hippocampus, and basal ganglia was observed in all but one case. Instances of laminar cortical necrosis were limited to cats exposed to hypoglycemic respiratory depression treated with hyperglycemia. Thus, treatment with hyperglycemia compared with euglycemia after hypoglycemic respiratory depression exposures significantly increased the brain injury scores (24 +/- 6 vs. 13 +/- 2 points; P < 0.05). This new experimental hypoglycemia model's contribution lies in recognizing additional factors that critically define the occurrence of hypoglycemic brain injury.
Journal of Cerebral Blood Flow & Metabolism 01/2000; 20(1):82-92. · 5.01 Impact Factor
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ABSTRACT: We presently examine the relation between histologic infarct size and neurologic deficit as endpoints and seek to clarify their sensitivity in defining stroke outcome. Neurologic deficits of 76 cats subjected to middle cerebral artery occlusion were assessed daily and correlated with the corresponding infarct sizes determined morphometrically after 2 weeks' survival. A five-item neurologic deficit score included the time elapsed until hemiparesis, and forced circling resolved (if ever), presence of impaired placing reactions and time elapsed until able to stand and being alert. We then evaluated the two endpoints' statistical powers to detect group differences using two sets of comparison groups. The neurologic deficit score correlated well with infarct size (r = 0.76, p < 0.001) and each of the individual deficit score components named above, in turn, correlated with decreasing power with infarct size. Even so, the number of study subjects required to achieve the same level of statistical significance in assessing group differences was two-fold greater when using the neurologic deficit than the infarct size data: Group sizes of eight and five animals were sufficient for significant infarct size differences while the groups needed be expanded to 15 and 10 animals to similarly achieve significant neurologic score differences. Thus, infarct size emerges as a more sensitive measure of stroke outcome than does the assessment of neurologic deficits.
Journal of Neuroscience Methods 09/1998; 83(2):151-7. · 1.98 Impact Factor
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ABSTRACT: The authors previously demonstrated, in a large-animal intracerebral hemorrhage (ICH) model, that markedly edematous ("translucent") white matter regions (> 10% increases in water contents) containing high levels of clot-derived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the concentrations of high-energy phosphate, carbohydrate substrate, and lactate in these and other perihematomal white and gray matter regions during the early hours following experimental ICH.
The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a physiologically controlled model in pigs (weighing approximately 7 kg each) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water contents were then measured in white and gray matter located ipsi- and contralateral to the hematomas, and metabolite concentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentrations increased two- to fivefold compared with control during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5 hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 micromol/g) at all times. In gyral gray matter overlying the hematoma, water contents and glycogen levels were significantly increased at 5 and 8 hours, whereas lactate levels were increased two- to fourfold at all times.
These results, which demonstrate normal to increased high-energy phosphate and carbohydrate substrate concentrations in edematous perihematomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present, lactate accumulation in edematous white matter is not caused by stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the blood entering the brain's extracellular space during ICH are several-fold higher than normal levels, the authors speculate, on the basis of work reported by Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced aerobic glycolysis and lactate is generated at a rate that exceeds utilization.
Journal of Neurosurgery 07/1998; 88(6):1058-65. · 2.96 Impact Factor
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ABSTRACT: The mechanisms underlying brain injury from intracerebral hemorrhage (ICH) are complex and poorly understood. To comprehensively examine pathophysiological and pathochemical alterations after ICH and to examine the effects of hematoma removal on these processes, we developed a physiologically controlled, reproducible, large-animal model of ICH in pigs (weight, 6 to 8 kg).
We produced lobar hematomas by pressure- controlled infusions of 1.7 mL of autologous blood into the right frontal hemispheric white matter over 15 minutes. We froze brains in situ at 1, 3, 5, and 8 hours after hematoma induction and cut coronal sections of hematoma assessment, morphological brain examination, and immunohistochemical and water content determinations.
At 1 hour after blood infusion, "translucent" white matter areas were present directly adjacent to the hematoma. These markedly edematous regions had a greater than 10% increase in water content (>85%) compared with the contralateral white matter (73%), and this increased water content persisted through 8 hours. In addition, these areas were strongly immunoreactive for serum proteins. Intravascular Evans blue dye failed to penetrate into the brain tissue at all time points, demonstrating that this serum protein accumulation and edema development were not due to increased blood-brain barrier permeability.
Experimental lobar ICH in pigs models a prominent pathological feature of human ICH, ie, early perihematomal edema. Our findings suggest that serum proteins, originating from the hematoma, accumulate in adjacent white matter and result in rapid and prolonged edema after ICH. This interstitial edema likely corresponds to the low densities on CT scans and the hyperintensities on T2-weighted MR images that surround intracerebral hematomas acutely after human ICH.
Stroke 03/1996; 27(3):490-7. · 5.73 Impact Factor
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Journal of Neurosurgery 02/1996; 84(1):146-8. · 2.96 Impact Factor
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Stroke 06/1994; 25(5):1082-3. · 5.73 Impact Factor
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ABSTRACT: We examined the effects of serum glucose concentration during middle cerebral artery (MCA) occlusion in the cat on death rates in animals that died from hemispheric edema and on infarct size in animals that survived. We occluded that MCA permanently in some groups and released the clip after 8 h in others. By injecting or infusing glucose solutions, saline, or insulin, we maintained six animal groups steadily either hyper-, normo-, or slightly hypoglycemic before and for 6 or 8 h after permanent or 8-h temporary MCA occlusion. Studies with these groups revealed a distinct optimal outcome with normoglycemic animals. In three additional groups, we altered the glycemia after permanent occlusion from hyper- to normo- or hypoglycemia and from normo- to hyperglycemia. Two of the three hypoglycemic groups (8-h reversible and permanent hyper- to hypoglycemic occlusions) yielded the worst outcomes in this study, with > 10x larger median infarcts than the best outcome group (normoglycemic permanent occlusion). Hyperglycemia also was detrimental and increased infarct size and mortality after permanent occlusion. Restoring the cerebral blood flow after 8 h of occlusion increased the death rate from hemispheric edema compared with a maintained occlusion. Following permanent MCA occlusion, converting from normo- to hyperglycemia or vice versa yielded outcomes intermediate between a sustained normo- or hyperglycemia. A regression analysis of the normo- and hyperglycemic groups and the two groups with glycemia altered after permanent occlusion showed a significant linear correlation between glycemia level at and 1 h after MCA occlusion and median infarct size.
Journal of Cerebral Blood Flow & Metabolism 03/1994; 14(2):227-36. · 5.01 Impact Factor
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ABSTRACT: Recent studies reveal success in treating spinal cord trauma with early, high-dose methylprednisolone. As in spinal cord research, failure to find therapeutic effects with steroids in studies of acute stroke treatment may reflect institution of treatment too late and at too low dosage. We presently test the efficacy of stroke treatment with methylprednisolone administered early and at high doses using a cat temporary middle cerebral artery occlusion model.
We occluded the middle cerebral artery for 4 hours in 24 pentobarbital-anesthetized cats. To enhance the probability of brain injury, we maintained the cats' serum glucose concentrations at high levels both during occlusion and for 6 hours afterward. Using a blinded, randomized study design, we treated 12 cats with methylprednisolone (30 mg/kg IV infused over 15 minutes starting 30 minutes after occlusion followed by 5.4 mg.kg-1.h-1 IV for the next 23 hours) and 12 control cats with vehicle. During and for 8 hours after occlusion, we monitored cerebral blood flow, brain and rectal temperatures, and multiple cardiovascular and blood compositional parameters. We assessed brain pathological outcome after animal survival for 4 days or after acute death from hemispheric edema.
Experimental and control animals showed similar early mortality rates (treated, 3/12; controls, 4/12). However, surviving methylprednisolone-treated cats (n = 9) showed a mean infarct size more than six times smaller than in the control animals (n = 8) (mean +/- SEM, 2.4 +/- 0.7% versus 15.6 +/- 6.2% of the ischemic territory, respectively; P < .05). The methylprednisolone-treated animals also showed less marked reduction in cerebral blood flow during ischemia than did the controls (mean +/- SEM, 58 +/- 5% versus 74 +/- 4%; P < .005).
Administering methylprednisolone at high doses early after onset of ischemia significantly reduces tissue injury in cats that survive 4 days of temporary middle cerebral artery occlusion. This improvement in outcome occurs in the setting of significant increases in ischemic cerebral blood flow. However, methylprednisolone treatment did not reduce hemispheric edema in animals that died early after temporary middle cerebral artery occlusion.
Stroke 02/1994; 25(2):487-92; discussion 493. · 5.73 Impact Factor
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ABSTRACT: Hyperglycemia aggravates brain pathologic outcome following middle cerebral artery (MCA) occlusion in cats. We presently determined if hyperglycemia during occlusion leads to high lactic acid accumulations in the ischemic MCA territory. We measured brain metabolite concentrations in 14 MCA territory sites at 0.5 and 4 h following occlusion in hyper- (20 mM) and normoglycemic (5 mM) cats and correlated these results with previous brain pathologic findings. Hyper- versus normoglycemia during MCA occlusion resulted in significantly higher lactate concentrations in the ischemic territory and more numerous loci with lactates greater than 17 mumol/g. At 0.5 h of occlusion, ATP levels were lower in normoglycemic cats, while at 4 h, ATP was similarly reduced (40%) in both glycemia groups. At 4 h, PCr was more reduced in hyperglycemics secondary to a greater brain tissue acidosis. Carbohydrate substrates at 0.5 h were more markedly depleted in normoglycemics, likely limiting lactate accumulation (34.3% versus only 5.0% of sites in hyperglycemics with glucose less than 0.5 mumol/g). Although lactate was markedly elevated at both 0.5 and 4 h in hyperglycemic ischemic territories, clip release at 4 versus 0.5 h yields a significantly poorer brain pathologic outcome. Correspondingly, intracellular pH, calculated from the creatine kinase equilibrium, was more markedly depressed at 4 than at 0.5 h of occlusion, demonstrating a time-dependent dissociation between tissue lactate and hydrogen ion accumulations. The present findings show that following MCA occlusion (a) hyperglycemia increases the magnitude and topographic extent of marked tissue lactic acidosis, (b) infarct size following 0.5 h of clip release correlates more closely with tissue acidosis than with lactate concentrations, (c) ischemic tissue ATP concentrations correlate poorly with infarct size, (d) normoglycemia limits lactate accumulation during focal ischemia because tissue glucose is depleted, and (e) early during ischemia, tissue buffering or antiport mechanisms may prevent marked increases in intracellular hydrogen ion activity.
Journal of Cerebral Blood Flow & Metabolism 04/1992; 12(2):213-22. · 5.01 Impact Factor
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ABSTRACT: This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion.
Prospective, controlled laboratory investigation.
One hundred six pentobarbital-anesthetized cats.
The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion.
Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage.
Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation.
Annals of Emergency Medicine 03/1992; 21(2):120-6. · 4.13 Impact Factor
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ABSTRACT: Hyperglycemic, but not normoglycemic cats exposed to anoxia develop neurologic signs following reoxygenation including fasciculations, focal and tonic-clonic seizures and coma after a symptom-free period. These symptomatic hyperglycemic cats may develop brain edema and will show diffuse neuronal injury or brain infarction depending on length of survival. Brain mitochondria isolated from symptomatic but not asymptomatic cats have decreased ADP- and uncoupler-stimulated oxygen consumption rates. Since impaired respiration could result from altered electron transport chain function, we measured cytochrome c, b, and aa3 concentrations and the activities of the five electron transfer complexes in isolated brain mitochondria. In symptomatic cats marked alterations were present in particular in complex IV, cytochrome oxidase, with a 57% reduction in activity and a 45% reduction in prosthetic group (cytochrome aa3) concentrations. Less marked reductions in other segments of the chain included 27% and 41% decreases, respectively, in cytochrome c concentrations and in electron transfer complex II, succinate:ubiquinone oxidoreductase activity. Cytochrome b concentrations and complex I, II and V activities were unchanged. Small but significant decreases in cytochrome aa3 concentrations (18%) and cytochrome oxidase activity (20%) were also present in mitochondria from postanoxic hyperglycemic cats prior to appearance of neurologic signs. These results indicate that delayed decreases in the activities of specific electron transfer complexes are correlated with impaired mitochondrial respiration and neurologic deterioration in postanoxic hyperglycemic cats. However, it is presently unclear if these postanoxic brain mitochondrial alterations are primary or secondary events in the development of brain injury.
Journal of the Neurological Sciences 01/1991; 100(1-2):142-51. · 2.35 Impact Factor
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ABSTRACT: We previously demonstrated markedly inhibited brain mitochondrial respiration only in cats that (a) were hyperglycemic at anoxia and (b) had neurologic signs, i.e., fasciculations in tongue or facial muscles or focal seizures following reoxygenation. However, since the relationship between time of onset of mitochondrial dysfunction and neurologic signs was unclear, in the present study we killed postanoxic cats immediately when signs first appeared. Cerebrocortical homogenates and isolated brain mitochondria only from symptomatic cats showed markedly inhibited substrate-, ADP-, and uncoupler-stimulated respiration rates. Cytochrome oxidase activity and cytochrome aa3 concentrations were also markedly reduced in these mitochondria. Since brain mitochondrial function was impaired when neurologic signs first appeared, mitochondrial alterations are an important early organellar change correlated with development of neurologic deterioration following anoxia.
Journal of Cerebral Blood Flow & Metabolism 06/1990; 10(3):417-23. · 5.01 Impact Factor
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Stroke 03/1990; 21(2):357-8. · 5.73 Impact Factor
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ABSTRACT: Brain oedema is an important aspect of infarction from cerebrovascular occlusion. In a cat stroke model where the middle cerebral artery (MCA) was reversibly or permanently occluded, we analyzed the incidence of fatal hemispheral oedema in 35 normo- (6 mM) and 35 hyperglycaemic (20 mM for 6 hours) animals, with (N = 45) and without (N = 25) restoration of blood flow with clip release at 4 and 8 hrs of occlusion. Fatal hemispheral oedema occurred in 23% of cats (16/70) while hyperglycaemia, for one, and restoration of blood flow, for another, each quadrupled its occurrence. Further, evidence of remote oedema in the form of posterior cingulate cortical pressure atrophy from transtentorial herniation was found in animals that were allowed to survive for 2 weeks and that exhibited infarcts that affected 12 to 95% of the MCA territory. Thus, hemispheral oedema in association with MCA occlusion developed sufficiently markedly as to cause transtentorial herniation in 47% of all cats (33/70). We carried out biochemical analyses in 14 hyper- and 10 normoglycaemic cats after 4 hrs of MCA occlusion for ATP, phosphocreatine (PCr), lactate, glucose and glycogen. The biochemical findings then were correlated with the occurrence of reperfusion oedema following clip release after 4 hrs of occlusion point-by-point in the brains. Linear regression analyses of the brain metabolic and pathologic data revealed highly significant (p less than 0.001) correlations of acute oedema with brain tissue ATP and PCr reductions less than 1.5 microM/g, with lactic acid accumulation greater than 20 microM/g and with the extents of reduction in brain tissue glucose concentrations in the ischaemic territories.(ABSTRACT TRUNCATED AT 250 WORDS)
Acta neurochirurgica. Supplement 02/1990; 51:226-9.
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ABSTRACT: Hyperglycemia is associated with three- to fourfold larger infarcts than normoglycemia following permanent middle cerebral artery occlusion in cats. We investigated the effects of glycemia on brain outcome when middle cerebral artery blood flow was restored (clip release) after 4 hours of occlusion. Seven of 13 hyperglycemic (22 mM) and one of 12 normoglycemic (6 mM) anesthetized cats developed total middle cerebral artery territory infarcts and hemispheric edema and died of brainstem compression. The remaining six and 11 cats recovered fully and later showed no or only small infarcts. Compared with permanent occlusion, restoration of blood flow after 4 hours reduced infarct volume in all normoglycemic and hyperglycemic cats that survived, but caused a much higher proportion (54% vs. 17%) of hyperglycemic and, for the first time, one normoglycemic cat, to die of infarct extension, hemorrhagic infarct conversion, and total territory edema. Thus, clip release after 4 hours caused some cats to show reduced and others to show augmented tissue damage. Rendering cats hyperglycemic substantially worsened their outcome after reperfusion by increasing their death rate from total territory edema sevenfold. Our results demonstrate that risk/benefit analyses for recanalization efforts in humans should take serum glucose concentrations into account.
Stroke 01/1990; 20(12):1707-15. · 5.73 Impact Factor
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ABSTRACT: Hyper- but not normoglycemic cats exposed to 8 min of anoxia show neurologic signs (fasciculations, myoclonic jerks, seizures) that develop after a symptom-free period. We examined brain mitochondrial function and metabolite concentrations at 0, 1, 3, and 5 h following exposure to anoxia, to correlate biochemical findings with the presence ("symptomatic") or absence ("presymptomatic") of neurologic signs. Brain mitochondria isolated postexposure only from symptomatic cats showed markedly decreased (-50%), state 3 (ADP-stimulated), and uncoupler-stimulated respiration rates with NAD- and FAD-linked substrates. Respiratory control and ADP/oxygen (ADP/O) ratios remained unchanged, indicating, respectively, that coupling and efficiency of ATP synthesis were preserved. Thus, inhibition of electron transport chain function, not phosphorylative activity, may be rate limiting for respiration. During anoxia, hyperglycemic cats showed higher brain lactate levels (26 versus 20 mumol/g), but similar ATP and phosphocreatine concentrations, compared with normoglycemic cats. After exposure, in all animals lactate and phosphocreatine were restored to control levels, whereas ATP remained at 85%. Cats that became symptomatic demonstrated four- to sixfold increases in lactate and 50% reductions in phosphocreatine. At 3 and 5 h postexposure, symptomatic animals showed significant reductions in ATP concentrations. We conclude that although initially asymptomatic, hyperglycemic cats exposed to anoxia undergo a neurologic deterioration over several hours following reoxygenation that is correlated with inhibition of mitochondrial respiration, increases in tissue lactate, and decreases in energy state.
Journal of Neurochemistry 06/1989; 52(5):1407-17. · 4.06 Impact Factor
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ABSTRACT: Both heart and brain are at risk for damage from asphyxia. However, these 2 organs' relative injury-thresholds have remained poorly defined. The present study using 16 anesthetized newborn piglets attempts to separate brain and heart damaging exposures from those that leave these organs unaffected. The hypoxic exposure (mean PaO2 = 3.6 +/- 0.6 kPa (27 mmHg) lasted for an average duration of 40 minutes and was associated with hypotension less than 4.7 kPa (35 mmHg) MABP. For brain damage assessment, 9 piglets that survived greater than 12 hours following resuscitation permitting histologic evaluation were used. For heart outcome assessment, those piglets that developed a postexposure, secondary hypotension to less than 4.7 kPa (35 mmHg) were compared to those without excluding 3 with uncertain cause of death. BRAIN-RESULTS: Six piglets remained brain intact while 3 exhibited brain edema and diffuse neuronal damage. The damaged animals' exposures differed from those that remained brain intact in sustaining significantly lower lowest MABPs (1.6 +/- 0.1 vs 3.3 +/- 0.4 kPa (12 vs 25 mmHg] and longer durations of MABP below 3.3 kPa (25 mmHg): 6 vs 1 min. and below 2.7 kPa (20 mmHg): 4 vs 0 min. HEART-RESULTS: Six of 13 animals developed marked delayed post-exposure hypotension requiring 5 to be killed prior to complete cardiovascular collapse. The only significant difference observed during exposure differentiating the two outcome groups (blood pressure maintenance vs cardiogenic shock) was the latter's more marked systemic acidosis (lowest mean arterial blood pH: 6.61 +/- 0.10 vs 6.91 +/- 0.10). These results suggest the brain is at risk for damage during hypoxia only when accompanied by an extreme lowering of blood pressure and the heart when accompanied by a severe acidosis. Further, the heart and brain need not both be damaged by the same hypoxic exposure. Contrary to common belief, the brain is not readily damaged from hypoxia alone absent marked circulatory changes.
Biomedica biochimica acta 02/1989; 48(2-3):S143-8.
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ABSTRACT: We investigated the influence of serum glucose concentration on infarct size following middle cerebral artery occlusion in cats. These animals were deprived of food for 48 hours and infused with 1) saline for 1 hour before and 8 hours after occlusion (n = 8), 2) 10% glucose solution for 1 hour before and 6 hours after occlusion and saline for 2 additional hours (n = 8), or 3) 10% glucose for 1 hour before and saline for 8 hours after occlusion (n = 5). Nineteen cats killed after 2 weeks' survival were subjected to morphometric infarct size determinations. Eight normoglycemic and 11 hyperglycemic cats exhibited infarcts affecting 10.2 +/- 3.4% and 29.5 +/- 6.5% (mean +/- SEM) of their middle cerebral artery territories, respectively (p less than 0.02). Cats of the two hyperglycemic groups showed similarly sized infarcts. However, two of eight (25%) of cats with preocclusion and postocclusion hyperglycemia died 8 and 24 hours after occlusion with infarction of the entire middle cerebral artery territory, marked hemispheral edema, and brainstem compression. Our results demonstrate that serum glucose concentration at the time of large cerebral vessel occlusion influences stroke outcome.
Stroke 06/1988; 19(5):623-30. · 5.73 Impact Factor
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ABSTRACT: We report the neuropathologic findings in a 63-year-old white male with a history of birth asphyxia, cerebral palsy, seizures and mild mental retardation in conjunction with similar brain pathologic findings in animal models of perinatal asphyxia. The human case showed a left cerebral hemispheric hemiatrophy associated with an extensive ulegyria involving all cerebral lobes on that side and a single microscopic focus of cortical atrophy in the right hemisphere. Among a large number of experimental perinatal asphyctic exposures only an occasional animal, like the human case described, showed unilateral hemispheric injury with softening and necrosis if examined early and ulegyria with hemispheric hemiatrophy if examined late. The present paper suggests that perinatal asphyxia under specific pathophysiologic conditions may cause unilateral brain injury. Our experimental studies suggest the specific condition of perinatal asphyxia potentially causing unilateral or asymmetrical brain damage is marked hypoxemia combined with substantial reductions in blood pressure but without circulatory collapse. Given these conditions, the asymmetry of the brain damage likely reflects fetal head position within the gravitational field relative to the heart. With disturbed cerebral blood flow autoregulation from asphyxia, the gravitational field likely accentuates the ischemia of those brain areas most elevated above the level of the heart. Thus, we postulate head position may play a pivotal role in defining brain regions that are damaged in hypotensive perinatal asphyxia. This interpretation may affect the intensive care of hypoxemic, hypotensive newborns aimed at minimizing the risk of brain damage.
Pediatric neuroscience 02/1988; 14(3):114-9.
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Neurology 08/1987; 37(7):1267-8. · 8.31 Impact Factor
