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Hypertonic Sodium Lactate to Alleviate Functional Deficits Following Diffuse Traumatic Brain Injury: An Osmotic or a Lactate-Related Effect?

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Abstract

Background

There has been growing interest in the use of hypertonic sodium lactate (HSL) solution following traumatic brain injury (TBI) in humans. However, little is known about the effects of HSL on functional deficits with respect to the hyperosmotic nature of HSL.

Methods

We have compared the effects of HSL solution and isotonic saline solution using sensorimotor and cognitive tests for 14 days post-trauma in animals. Thirty minutes after trauma (impact-acceleration model), anesthetized rats were randomly allocated to receive a 2-h infusion of isotonic saline solution (TBI-saline group) or HSL (TBI-HSL group) (n = 10 rats per group). In another series of experiments using a similar protocol, the effects of equiosmolar doses of HSL and hypertonic saline solution (HSS) were compared in TBI rats (n = 10 rats per group). Blood lactate and ion concentrations were measured during the 2-h infusions.

Results

Compared to the TBI-saline group, the TBI-HSL group had a reduced latency to complete the adhesive removal test: 6 s (5–9) (median [25–75th centiles]) versus 13 s (8–17) on day 7, and 5 s (5–9) versus 11 s (8–26) on day 14 (P < 0.05), respectively, and a shorter delay to complete the radial arm maze test on day 7: 99 s (73–134) versus 176 s (127–300), respectively (P < 0.05). However, no differences were found between the TBI-HSL and TBI-HSS groups in neurocognitive tests performance. Compared to the TBI-saline group, the HSL and HSS groups had higher serum osmolality: 318 mOsm/Kg (315–321) and 315 mOsm/Kg (313–316) versus 307 mOsm/Kg (305–309), respectively (P < 0.05), and the HSL group had a higher serum lactate concentration: 6.4 mmol/L (5.3–7.2) versus 1.5 mmol/L (1.1–1.9) and 1.6 mmol/L (1.5–1.7), respectively (P < 0.05).

Conclusions

These results indicate that improvements in cognitive and sensorimotor tests with HSL infusion post-TBI could be related to elevation of serum osmolality, not to exogenous administration of lactate.

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Abbreviations

ADC:

Apparent diffusion coefficient

BVf:

Blood volume fraction

HSL:

Hypertonic sodium lactate

HSS:

Hypertonic saline solution

StO2 :

Brain tissue oxygen saturation

TBI:

Traumatic brain injury

VSI:

Vessel size index

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Acknowledgements

The authors wish to thank Vasile Stupar and Nora Collomb (IRMaGe) for their technical help with the experiments.

Funding

This study was conducted at the INSERM U1216/Grenoble Institut des Neurosciences and was partly funded by the “Fondation des Gueules Cassées” (Paris, France). Brain MRI was performed at the Grenoble MRI Facility (IRMaGe) that is partly funded by the French program “Investissement d'Avenir” (Agence Nationale de la Recherche, Grant Infrastructure d'Avenir en Biologie Santé ANR-11-INBS-0006).

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Authors and Affiliations

  1. Inserm U1216, Department of Anesthesia and Critical Care, CHU Grenoble Alpes, Grenoble Institut Neurosciences, GIN, Univ. Grenoble Alpes, Grenoble, France

    Thibaud Crespy, Maxime Durost, Pierre Fricault, Pierre Bouzat & Jean-François Payen

  2. Inserm U1216, Grenoble Institut Neurosciences, GIN, Univ. Grenoble Alpes, Grenoble, France

    Benjamin Lemasson & Emmanuel L. Barbier

Authors
  1. Thibaud Crespy
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  2. Maxime Durost
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  3. Pierre Fricault
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  5. Pierre Bouzat
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  7. Jean-François Payen
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Correspondence to Jean-François Payen.

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The authors declare that they have no competing interests.

Ethical Approval

The study design was approved by the Internal Evaluation Committee for Animal Welfare and Rights (Ref#2017030614362942). Experiments were performed in accordance with the guidelines of the French Government (licenses 380819 and B3851610008). All applicable institutional and national guidelines for the care and use of animals were followed.

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Crespy, T., Durost, M., Fricault, P. et al. Hypertonic Sodium Lactate to Alleviate Functional Deficits Following Diffuse Traumatic Brain Injury: An Osmotic or a Lactate-Related Effect?. Neurocrit Care 34, 795–803 (2021). https://doi.org/10.1007/s12028-020-01090-3

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