1. The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review.
- Author
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Hollyer, Tristan R., Bordoni, Luca, Kousholt, Birgitte S., Luijk, Judith, Ritskes‐Hoitinga, Merel, and Østergaard, Leif
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LACTATES , *BRAIN physiology , *BRAIN function localization , *MICROCIRCULATION , *BLOOD circulation - Abstract
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%5flactate%5fprotocol.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/. This systematic review evaluated the role of lactate in the cerebral microcirculation across in vitro, in vivo, and clinical studies. We identified that when administered exogenously, at 5 mmol/kg or higher, lactate is an initiator of cerebral hyperemia and acts as an augmenter of functional hyperemia at lower doses. These findings shine light on novel aspects of lactate biochemistry in the brain. This manuscript was awarded with the Pre‐registration Badge. The pre‐registration protocol can be accessed at http://www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer%5flactate%5fprotocol.aspx. For more information see: https://cos.io/our-services/open-science-badges/ [ABSTRACT FROM AUTHOR]
- Published
- 2019
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