Effects of lactate on glucose metabolism of developing rat brain

Miller, Alexander L.; Kiney, Colleen A.; Staton, Donna M.

doi:10.1016/0165-3806(84)90006-3

Cited by 23 publications

(11 citation statements)

References 26 publications

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“…The presence of brain acidosis together with hyperlac-, . , tatemia requires a pathological condition(s), because physiologically hyperlactatemia does not result in acidosis (Miller et al, 1984). In line with the findings for adults, infants who had died suddenly due to accidents had low lactate and high pH values in the brain, whereas those infants who might have been exposed to hypoxia had the converse, implying that infants respond to insult(s) in the same way as adults.…”

Section: Discussionsupporting

confidence: 66%

Postmortem Human Brain pH and Lactate in Sudden Infant Death Syndrome

Butterworth

Tennant

1989

Journal of Neurochemistry

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Lactate and pH were measured in frontal and temporal cortex, cingulate gyrus, and caudate nucleus in brains from sudden infant death syndrome (SIDS) cases, control infants, and control adults. Both the lactate levels and the pH values were significantly correlated (p less than 0.001) between the four brain areas, whereas lactate and pH values were significantly correlated within each brain area (p less than 0.001) with a value of pH 7.2 for zero lactate. The lactate concentration in heart blood was significantly correlated with brain lactate (p less than 0.001). Adult sudden death cases (heart attacks) had low lactate and high pH values, whereas agonal state cases had high lactate and low pH values. Control infants who had died because of accidents also had low lactate and high pH values, but infants who might have been exposed to hypoxia before death had high lactate and low pH values. SIDS cases fell into two groups: the first, consisting of all victims over 30 weeks of age and about one-half to two-thirds of those aged less than 30 weeks, had low lactate and high pH values; the second group, consisting of about one-third to one-half of those less than 30 weeks old, had high lactate and low pH values. The changes in lactate levels and pH values indicate that the majority of SIDS cases had died suddenly, but that a sizeable minority had been exposed to hypoxia prior to death.

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Section: Discussionsupporting

confidence: 66%

Postmortem Human Brain pH and Lactate in Sudden Infant Death Syndrome

Butterworth

Tennant

1989

Journal of Neurochemistry

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“…Glutamate and GABA depletion monitored by 1 H NMR spectroscopy correlates with increased brain glutaric acid levels and may translate for use in human GA-I to detect risk of brain injury. Glutamate depletion in this mouse model is consistent with reduced brain glucose utilization, as previously shown with immature rats (36). Reduced brain glucose utilization was previously shown in human GA-I using 18 fluoro-2-deoxyglucose uptake studies (37), indicating that glutamate levels may also be compromised in human GA-I with encephalopathy.…”

Section: Figuresupporting

confidence: 61%

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Zinnanti¹,

Lazović²,

Housman³

et al. 2007

J. Clin. Invest.

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Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I.

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“…(37,38) or i.p. (31,39) lactate administration. Under these experimental conditions it is likely that exogenous lactate is oxidized to pyruvate (coupled to the reduction of cytosolic NAD ϩ to NADH) and used in mitochondria instead of or in addition to pyruvate produced by glycolysis.…”

Section: Discussionmentioning

confidence: 99%

Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain

Mintun

Vlassenko

Rundle

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

132

104

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The factors regulating cerebral blood flow (CBF) changes in physiological activation remain the subject of great interest and debate. Recent experimental studies suggest that an increase in cytosolic NADH mediates increased blood flow in the working brain. Lactate injection should elevate NADH levels by increasing the lactate͞ pyruvate ratio, which is in near equilibrium with the NADH͞NAD ؉ ratio. We studied CBF responses to bolus lactate injection at rest and in visual stimulation by using positron-emission tomography in seven healthy volunteers. Bolus lactate injection augmented the CBF response to visual stimulation by 38 -53% in regions of the visual cortex but had no effect on the resting CBF or the wholebrain CBF. These lactate-induced CBF increases correlated with elevations in plasma lactate͞pyruvate ratios and in plasma lactate levels but not with plasma pyruvate levels. Our observations support the hypothesis that an increase in the NADH͞NAD ؉ ratio activates signaling pathways to selectively increase CBF in the physiologically stimulated brain regions.T he nature of the link between cerebral blood flow (CBF) and energy metabolism is of great interest and importance but remains controversial despite decades of research and debate. Although CBF augmentation is still considered to be a hallmark of intensified neural activity, previous assumptions that behaviorally induced increases in local blood flow reflect similar local increases in oxidative metabolism (1) have been contradicted by brain imaging studies with positron-emission tomography (PET) (2, 3) and functional MRI (4). Fox and his colleagues (2, 3) demonstrated that in normal, awake adult humans, stimulation of the visual or somatosensory cortex results in dramatic increases in CBF but minimal increases in oxygen consumption. Increases in glucose utilization are similar to changes in CBF (3, 5). Although it is often assumed that the increase in CBF in neural activation is driven by a need for increased delivery of oxygen or glucose, it has been demonstrated in human subjects that the CBF response to physiological activation is not altered by either stepped hypoglycemia (6) or hypoxia (7). These results suggest that increased CBF during physiological brain activation does not occur to prevent a shortage of these metabolic substrates. Ido et al. (8) recently reported that CBF in activated rat brain is modified by changes in the plasma lactate͞pyruvate ratio: CBF was augmented when lactate͞pyruvate ratios were raised and attenuated when the ratios were lowered. Specifically, immediately after lactate bolus injection, the magnitude of the CBF increase associated with sensory stimulation approximately doubled. Based on the near equilibrium between the ratios of lactate͞pyruvate and cytosolic free NADH͞NAD ϩ (which reflects the local environment redox state) (9), they suggested that cytosolic free NADH is an important trigger or sensor of blood flow. The reoxidation of NADH to NAD ϩ is a step of vital importance for brain cells, especially in the acti...

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Effects of lactate on glucose metabolism of developing rat brain

Cited by 23 publications

References 26 publications

Postmortem Human Brain pH and Lactate in Sudden Infant Death Syndrome

Postmortem Human Brain pH and Lactate in Sudden Infant Death Syndrome

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain

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