Lactate as a Metabolite and a Regulator in the Central Nervous System

Proia, Patrizia; Liegro, Carlo Maria Di; Schiera, Gabriella; Fricano, Anna; Liegro, Italia Di

doi:10.3390/ijms17091450

Cited by 196 publications

(173 citation statements)

References 200 publications

(233 reference statements)

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“…Increased energy consumption is also required for neurons to engulf aggregates, repair damage or enter in apoptosis [84][85][86]. In these conditions, glucose transport to CNS is not sufficient to cover demand, and lactate is formed within astrocytes and sent to neurons for its complete oxidation [87,88]. As a result, the tissue pH decreases, which alters protein folding and induces aggregate formation, as observed with Amyloid-β [89].…”

Section: Als As a Misfolded Protein Diseasementioning

confidence: 99%

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Rodrı́guez¹,

Mahy²

2016

CMC

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Section: Als As a Misfolded Protein Diseasementioning

confidence: 99%

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Rodrı́guez¹,

Mahy²

2016

CMC

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“…; Proia et al . ). Given the complexity of the mechanisms that control cerebral blood flow (CBF) at a microvascular level (Attwell et al .…”

mentioning

confidence: 97%

The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review

Hollyer

Bordoni

Kousholt

et al. 2019

Journal of Neurochemistry

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Lactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre‐registration of a review protocol, we systematically searched the PubMed, EMBASE , and Cochrane databases for literature covering themes of ‘lactate’, ‘the brain’, and ‘microcirculation’. Abstracts were screened, and data extracted independently by two individuals. We excluded studies evaluating lactate in disease models. Twenty‐eight papers were identified, 18 of which were in vivo animal experiments (65%), four on human studies (14%), and six on in vitro or ex vivo experiments (21%). Approximately half of the papers identified lactate as an augmenter of the hyperemic response to functional activation by a visual stimulus or as an instigator of hyperemia in a dose‐dependent manner, without external stimulation. The mechanisms are likely to be coupled to NAD + / NADH redox state influencing the production of nitric oxide. Unfortunately, only 38% of these studies demonstrated any control for bias, which makes reliable generalizations of the conclusions insecure. This systematic review identifies that lactate may act as a dose‐dependent regulator of cerebral microcirculation by augmenting the hyperemic response to functional activation below 5 mmol/kg, and by initiating a hyperemic response above 5 mmol/kg. Open Science Badges This article has received a badge for * Pre‐registration * because it made the data publicly available. The data can be accessed at www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer_lactate_protocol.aspx . The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/ .

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“…In the attempt to provide alternative fuels to the brain, monitoring systemic changes is important to consider because of the pivotal role lactate plays in systemic signaling (Leverve, 2001; Mosienko et al, 2015; Proia et al, 2016; Mason, 2017). One limitation of our blood plasma metabolite analysis is that we were only able to report on 9 metabolites due to sensitivity limitations of NMR spectroscopy and limited blood plasma for NMR analysis.…”

Section: Discussionmentioning

confidence: 99%

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L‐lactate

Wolahan

Mao

Real

et al. 2017

J of Neuroscience Research

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Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant Sodium L-Lactate infusion in eleven moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of Sodium L-Lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from 0.92 to 1.84 mM) results in an increase in AVDlac from −0.078 mM to 0.090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury.

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Lactate as a Metabolite and a Regulator in the Central Nervous System

Cited by 196 publications

References 200 publications

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L‐lactate

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