Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury

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Abstract

Background:

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI).

Methods:

Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI–saline group) or HSL (TBI–HSL group). The sham–saline and sham–HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group).

Results:

Compared with the TBI–saline group, the TBI–HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI–HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047–0.098) vs 0.097 (0.079–0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71–79) vs 66% (55–73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5–38.4) nm vs 38.4 (31.0–47.5) nm; P < 0.01] compared with the TBI–saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI–HSL than in the TBI–saline group.

Conclusions:

These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects.

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