Glucose, lactic acid, and perinatal hypoxic-ischemic brain damage

Vannucci, Robert C.; Yager, Jerome Y.

doi:10.1016/0887-8994(92)90045-z

Cited by 84 publications

(40 citation statements)

References 74 publications

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“…Differential effects of glucose on neurons of varying maturity may also explain the differences in the effects of hyperglycemia in both human and animal models (21). If the mechanism of injury in hypoxia-ischemia is mediated through EAA receptors, as has been suggested by numerous investigators (22), then the discrepancy in the response to hyperglycemia after ischemia in different age groups might be explained by the ontogeny of the EAA receptors.…”

Section: Discussionmentioning

confidence: 96%

Postischemic Hyperglycemia Is Not Protective to the Neonatal Rat Brain

1992

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ABSTRACT. Brain glucose concentration during and after hypoxia-ischemia may be one of the variables affecting outcome of asphyxia1 insults. Glucose given before global ischemic forebrain iniurv to adult rats increases morehologic brain damage, i n d postischemic insulin administration reduces selective neuronal necrosis and cortical infarction. Because glucose infusions are routinely used in the clinical management of perinatal asphyxia, we evaluated the role of slucose administration after ischemic neuronal damage to neonatal rat brain. Sprague-Dawley rat pups (postnatal d 7) were subjected to left common carotid artery ligation followed by 2.5 h of 8% oxygen (Levine procedure). The experimental group was subdivided so that pups received either systemic injections of glucose or saline immediately after the hypoxic insult. Animals were killed on postnatal d 12 and brain areas of ipsi-and contralateral cortex and caudate were calculated from camera lucida tracings. There was no significant difference in size of brain infarction between postischemic glucose-treated and postischemic saline-treated pups. However, hypoxic-ischemic brains did show more severe neuronal damage when hyperglycemia was induced after asphyxia. Because postischemic hyperglycemia does not attenuate and may exacerbate injury, we recommend careful monitoring of blood glucose so that hyperglycemia does not occur during resuscitation of asphyxiated infants. (Pediatr Res 32: 489-493, 1992) Abbreviations NADPH-d, NADPH diaphorase EAA, excitatory amino acidNeurologic morbidity occurs in 20-30% of infants suffering acute perinatal asphyxia in the United States (I). The hypoxicischemic encepha~opath~ seen in survivors of pennatal asphyxia is a commonly encountered clinical problem and is thought to be the largest contributor to static encephalopathies in infants and children (2). Hypoglycemia is a frequent metabolic derangement among asphyxiated infants and has additive deleterious effects on the CNS sequelae of perinatal asphyxia (3-5). Standard resuscitation procedures use glucose infusions to correct posthypoxic hypoglycemia, but this procedure often results in hyperglycemia (6).

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Section: Discussionmentioning

confidence: 96%

Postischemic Hyperglycemia Is Not Protective to the Neonatal Rat Brain

1992

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“…However, acidosis may actually help minimize the energy mismatch that occurs during and immediately following ischemia by reducing metabolic demand in the face of a reduced substrate supply. Lactate accumulation during cerebral ischemia was also originally considered detrimental to postischemic recovery, but it now appears that the lactate anion itself is relatively benign (Siesjo, 1988~;Walz and Harold, 1989;Vannucci and Yager, 1992;Wagner et al, 1992 Mixed cultures (10-12 days) were derived from fetal rat hippocampi and contained both neurons and astrocytes (-1:l) (Tombaugh and Sapolsky, 1990a). Metabolic rates were recorded every 2 min with a silicon-based microphysiorneter (Molecular Devices, Menlo Park, CA, U.S.A.; see Raley-Susman et al, 1992).…”

Section: Acidosis As a Neuroprotective Agentmentioning

confidence: 99%

“…However, acidosis may actually help minimize the energy mismatch that occurs during and immediately following ischemia by reducing metabolic demand in the face of a reduced substrate supply. Lactate accumulation during cerebral ischemia was also originally considered detrimental to postischemic recovery, but it now appears that the lactate anion itself is relatively benign (Siesjo, 1988~;Walz and Harold, 1989;Vannucci and Yager, 1992;Wagner et al, 1992). Moreover, the use of lactate as a metabolic substrate in brain tissue has also been reported, both in vitro and in vivo (Hellmann et al, 1982; Schurr et a]., 1988u,b Mixed cultures (10-12 days) were derived from fetal rat hippocampi and contained both neurons and astrocytes (-1:l) (Tombaugh and Sapolsky, 1990a).…”

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confidence: 99%

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

Tombaugh

Sapolsky

1993

Journal of Neurochemistry

188

109

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Cerebral ischemia is one of the most common neurological insults. Many pathological events are undoubtedly triggered by ischemia, but only recently has it become accepted that ischemic cell injury arises from a complex interaction between multiple biochemical cascades. Tissue acidosis is a well established feature of ischemic brain tissue, but its role in ischemic neuropathology is still not fully understood. Within the last few years, new evidence has challenged the historically negative view of acidosis and suggests that it may play more of a beneficial role than previously thought. This review reintroduces the concept of acidosis to ischemic brain injury and presents some new perspectives on its neuroprotective potential. Key Words: Ischemia-infarction-Lactic acidosis-Excitotoxicity-Hippocampus-Selective neuronal necrosis -Energy metabolism. Experimental work aimed at understanding ischemic brain injury has highlighted numerous biochemical events that may mediate cell damage. Among these, tissue acidosis has received considerable attention. The history of the acidotic concept in ischemia research forms somewhat of an arch. A number of decades ago, cerebral acidosis was shown first to be a correlate of gross ischemic brain damage and was viewed later as a cause. At the height of interest in this topic, acidosis was considered among the principal mechanisms by which ischemic damage occurs (Myers, 1979;Siesjo, 1988~). Even so, it was clear that "cerebral ischemia" was not a single disease but any insult that involved a partial or complete reduction in cerebral blood flow. Various animal models of both focal and global ischemia have been widely used to study ischemic injury, but the question of whether tissue acidosis satisfactorily explains or even contributes to all forms of ischemic brain injury has never been formally addressed.Though acidosis is generally believed to underlie cerebral infarction, mounting evidence has suggested that acidosis does not contribute to the selective neuronal necrosis that occurs after transient ischemia or in the penumbra of developing infarcts. Not surprisingly, the earlier bias toward acidosis as a neurotoxic mechanism has waned. In this review, we briefly examine the evolution of the acidosis concept. We then focus on a recent and surprising series of in vitro observations suggesting that moderate acidosis may actually play a neuroprotective role during ischemia. We then discuss a striking and paradoxical implication of these data regarding the time course and possible mediators of selective neuronal injury following ischemia. THE TRADITIONAL BELIEF IN THE ACIDOTIC ROUTE OF ISCHEMIC DAMAGESupported by varying degrees of experimental evidence, many distinct mechanisms have been proposed to explain ischemic brain injury; of these, the concept of acidotic damage is perhaps the oldest. Early work suggested that metabolic acidosis, caused by continued glycolysis, was responsible for the severe tissue disruption seen in the postmortem brain (Friede and van Houten, 1961). D...

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“…This is because glucose and other available energy substrates can prevent brain damage, at least in the short term. 108 In addition to the loss of vascular autoregulation, hypoxia alters capillary permeability, and with reperfusion these capillaries may bleed leading to intracerebral or intraventricular haemorrhage. 109,110 The minimum duration of hypoperfusion necessary to produce brain damage in human infants is not yet conclusively established.…”

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confidence: 99%