Experimental cerebral ischemia in Mongolian gerbils

Bb, Mrsulja; Bj, Mrsulja; Spatz, Maria; Ito, Umeo; Jt, Walker; Klatzo, Igor

doi:10.1007/bf00685142

Cited by 98 publications

(20 citation statements)

References 20 publications

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“…Oxygen extraction does not stoichiometrically match that of glucose when blood flow is lowered causing large increases to occur in tissue lactate levels, which may become 20-fold higher than normal due to preferential glycolytic activity (Ginsberg et al, 1996;Belayev et al, 1997;Hå berg et al, 1998) together with activation of glycogenolysis (Mrsulja et al, 1975;Kogure et al, 1977;Gross and Ferrendelli, 1980). The magnitude of the rise in lactate level in severely ischemic tissue varies in proportion to the pre-ischemic concentration of glucose in blood, and lactate levels rise much higher in penumbra than the core due to residual blood flow and continued supply of glucose, especially during hyperglycemia (Folbergrova et al, 1992).…”

Section: Bioenergetics Of Ischemia In Intact Brain Tissues: Acute Phamentioning

confidence: 94%

Astrocytic contributions to bioenergetics of cerebral ischemia

Dienel

Hertz

2005

Glia

135

107

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Astrocytes are multifunctional cells that interact with neurons and other astrocytes in signaling and metabolic functions, and their resistance to pathophysiological conditions can help restrict loss of tissue after an ischemic event provided adequate nutrients are supplied to support their requirements. Astrocytes have substantial oxidative capacity and mechanisms to upregulate glycolytic capability when respiration is impaired. An astrocytic enzyme that synthesizes a powerful activator of glycolysis is not present in neurons, endowing astrocytes with the ability to sustain ATP production under restrictive conditions. The monocarboxylic acid transporter (MCT) isoforms predominating in astrocytes are optimized to facilitate very large increases in lactate flux as lactate concentration increases within (1-3 mM) and above (>3 mM) the normal range. In sharp contrast, the major neuronal MCT serves as a barrier to increased transmembrane transport as lactate rises above 1 mM, restricting both entry and efflux. Lactate can serve as fuel during recovery from ischemia but direct evidence that lactate is oxidized by neurons (vs. astrocytes) to maintain synaptic function is lacking. Astrocytes have critical roles in regulation of ionic homeostasis and control of extracellular glutamate levels, and spreading depression associated with ischemia places high demands on energy supplies in astrocytes and contributes to metabolic exhaustion and demise. Disruption of Ca2+ homeostasis, generation of oxygen free radicals and nitric oxide, and mitochondrial depolarization contribute to astrocyte death during and after a metabolic insult. Novel pharmaceutical agents targeted to astrocytes and hyperoxic therapy that restores penumbral oxygen level during energy failure might improve postischemic outcome.

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Section: Bioenergetics Of Ischemia In Intact Brain Tissues: Acute Phamentioning

confidence: 94%

Astrocytic contributions to bioenergetics of cerebral ischemia

Dienel

Hertz

2005

Glia

135

107

View full text Add to dashboard Cite

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“…These animals are referred to as "sensitive" 3 or "symptom-positive." 9 The other 40% are "symptom-negative" animals which do not exhibit any gross neurological deficits although there are mild disturbances of energy state and of water and electrolyte homeostasis. 10 These animals were selected for investigating the occurrence of hippocampal injury and for studying the question if such injury is associated with disturbances of learning behaviour.…”

mentioning

confidence: 99%

Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain.

Bothe¹,

Bosma²,

Hofer³

et al. 1986

Stroke

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SUMMARYThe effect of selective injury of hippocampal neurons on the consolidation of memory traces was studied in gerbils (meriones unguiculatus) after production of mild cerebral ischemia. The right carotid artery was permanently ligated, and animals without gross neurological deficits ("symptom-negative" gerbils) were selected. Eight days and eight weeks after vascular ligation, cell counts of hippocampal neurons were carried out and correlated with regional blood flow and the acquisition of operant behaviour. Eight days after carotid artery occlusion, learning behaviour was significantly impaired although the number of hippocampal neurons had not changed and blood flow had even increased above normal. After eight weeks, learning behaviour and blood flow were normal but now a significant loss of pyramidal neurons was present in the CA1 and CA2 sectors of the hippocampus. Our observations demonstrate that it is possible to detect subtle functional disturbances by appropriate behavioural investigation before manifestation of selective injury of the hippocampus. Recovery of integrative function, despite persistent cellular damage, provides further evidence for central nervous plasticity.

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“…44 Briefly, mean arterial pressure (MAP) was rapidly reduced to about 50 torr by intravenous bolus injection of trimethaphan camsylate (Arfonad, Roche laboratories, Nutley, NJ).…”

Section: Mmentioning

confidence: 99%

Post-ischemic hypermetabolism in cat brain.

Nemoto¹,

Hossmann²,

Cooper³

1981

Stroke

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SUMMARY Delayed postischemk brain hypoperfusion and hypennetabolism are likely detrimental factors to neurologic recovery after transient global brain ischemia and may be mediated by catecholaraines acting via adrenergic receptors. We evaluated the effects of alpha and beta receptor blockade on cerebral blood flow (CBF) and metabolism after 16 min transient global brain ischemia.Ischemia was induced by arterial hypotension and a high pressure neck tourniquet in 13 anesthetized cats. Six cats were untreated, 4 received propranoloi 1 mg/kg, IV and 3 a combination of propranolol and phentolamine, one mg/kg injected one min before recircnlation. Total CBF was measured by continuous monitoring of cerebral venous "*Xe clearance after bolus intra-arterial injection. Arterial and cerebral venous oxygen, glucose and lactate were measured. Cerebral cortex glucose and lactate were measured 3 hours post-ischemia after in situ freezing with liquid N,. The cerebral cortex of 3 cats anesthetized, but not subjected to ischemia, was similarly frozen and analyzed for glucose and lactate.Total CBF was relatively constant for up to 3 h post-ischemia in all groups, but significant changes in fast and slow-flow rates and compartment sizes were observed. In untreated cats, the normal 60/40 percent relative weight of the fast and slow-flow compartments was reversed to 30/70 percent by 1 hr post-ischemia. Propranolol attenuated the size of the fast-flow compartment in the first 30 min post-ischemia which was partially restored by phentolamine. Brain oxygen consumption Increased 2 to 3-fold by 1 h post-lscbemia in all groups. Propranolol compromised CBF and impaired glucose and lactate oxidation which was partly reversed by phentolamine.We concluded that within the first 30 min post-ischemia, beta, and to a lesser extent, alpha receptors predominate in the modulation of cerebrovascular tone. By 1 h post-ischemia, however, adrenergic modulation of cerebrovascular tone is lost. Delayed post-ischemic hypermetabolism unlike stress-induced, but like hypoxia-induced hypermetabolism is only partially affected by beta blockade. Propranolol apparently compromises brain oxygen consumption secondary to a reduction in brain O, supply while phentolamine improves perfusion and oxygen consumption. Methods and MaterialsSixteen cats of either sex, 3 to 4 kg body weight, were anesthetized with halothane, 4 percent in oxygen, and glass cannulae were tied into the tracheas. The cats were immobilized with pancuronium bromide (0.4 mg) and mechanically ventilated on halothane 1 percent, oxygen 33 percent, and nitrogen 66 percent. Respiratory rates and tidal volumes were adjusted to maintain continuously monitored end-tidal CO, between 4 and 5 percent. Rectal temperature and electrocardiogram were continuously monitored.Polyethylene catheters inserted in femoral veins and arteries were used for drug infusion, intravenous fluid replacement (5 percent dextrose/0.45 percent NaCl, 3 to 5 ml/kg hour), arterial pressure monitoring, blood sampling and reinfusion of c...

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Experimental cerebral ischemia in Mongolian gerbils

Cited by 98 publications

References 20 publications

Astrocytic contributions to bioenergetics of cerebral ischemia

Astrocytic contributions to bioenergetics of cerebral ischemia

Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain.

Post-ischemic hypermetabolism in cat brain.

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