Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat

R. Holloway, Z. Zhou, H. B. Harvey, J. E. Levasseur, A. C. Rice, D. Sun, R. J. Hamm, Ross Bullock

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background. In previous studies, it has been shown that intravenous lactate therapy can improve brain neurochemistry, adenosine triphosphate (ATP) generation and outcome after traumatic brain injury (TBI) in rats. In this study, we examined: (1) four L-lactate concentrations to determine the optimal therapeutic dose post TBI in terms of cognitive function; (2) ATP production after TBI for the L-lactate concentration found to be the optimal dose; (3) the possible production of lactic acidosis with the highest L-lactate concentration tested. Methods. Thirty minutes following a fluid percussion injury (FPI) over the left cerebral hemisphere, the animals received an intravenous infusion of 10, 28, 100, or 280 mM L-lactate (n = 10 for each group) for 3 h at a rate of 0.65 ml/h. Shams and control injured animals received a saline infusion. At 11-15 days post injury, cognitive deficits were examined using the Morris Water Maze (MWM) test. Three groups of rats were used for ATP analysis: shams, injured + saline infusion, and injury + the optimal lactate dose as determined by the MWM (n = 4/group). Additionally, a group receiving 280 mM L-lactate (n = 5) and one receiving a saline infusion (n = 3) were monitored for arterial blood variables and blood pressures. Findings. In the MWM test, only the 100 mM L-lactate-treated injured animals showed a significant reduction in cognitive deficits when compared to saline-treated injured animals (p ≤ 0.05). In the ATP study, injured animals without treatment had a 53% reduction in ATP level in the ipsilateral cortex, while animals with 100 mM lactate treatment had a 28% reduction. (p ≤ 0.05). No lactic acidosis was induced by the intravenous infusion of 280 mM L-lactate. Conclusions. This study indicates that the intravenous infusion of 100 mM L-lactate provided the optimal concentration of the substrate to ameliorate cognitive impairment, probably via the regeneration of ATP following TBI in rats.

Original languageEnglish
Pages (from-to)919-927
Number of pages9
JournalActa Neurochirurgica
Volume149
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

brain damage
lactates
Cognitive Therapy
rats
Rats
therapy
Lactic Acid
Brain
Animals
adenosine triphosphate
animals
Adenosine Triphosphate
acidosis
Intravenous Infusions
Lactic Acidosis
Water
Blood pressure
dosage
Wounds and Injuries
Traumatic Brain Injury

Keywords

  • ATP
  • Cognitive deficits
  • L-lactate
  • TBI

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Holloway, R., Zhou, Z., Harvey, H. B., Levasseur, J. E., Rice, A. C., Sun, D., ... Bullock, R. (2007). Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat. Acta Neurochirurgica, 149(9), 919-927. https://doi.org/10.1007/s00701-007-1241-y

Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat. / Holloway, R.; Zhou, Z.; Harvey, H. B.; Levasseur, J. E.; Rice, A. C.; Sun, D.; Hamm, R. J.; Bullock, Ross.

In: Acta Neurochirurgica, Vol. 149, No. 9, 01.09.2007, p. 919-927.

Research output: Contribution to journalArticle

Holloway, R, Zhou, Z, Harvey, HB, Levasseur, JE, Rice, AC, Sun, D, Hamm, RJ & Bullock, R 2007, 'Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat', Acta Neurochirurgica, vol. 149, no. 9, pp. 919-927. https://doi.org/10.1007/s00701-007-1241-y
Holloway, R. ; Zhou, Z. ; Harvey, H. B. ; Levasseur, J. E. ; Rice, A. C. ; Sun, D. ; Hamm, R. J. ; Bullock, Ross. / Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat. In: Acta Neurochirurgica. 2007 ; Vol. 149, No. 9. pp. 919-927.
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abstract = "Background. In previous studies, it has been shown that intravenous lactate therapy can improve brain neurochemistry, adenosine triphosphate (ATP) generation and outcome after traumatic brain injury (TBI) in rats. In this study, we examined: (1) four L-lactate concentrations to determine the optimal therapeutic dose post TBI in terms of cognitive function; (2) ATP production after TBI for the L-lactate concentration found to be the optimal dose; (3) the possible production of lactic acidosis with the highest L-lactate concentration tested. Methods. Thirty minutes following a fluid percussion injury (FPI) over the left cerebral hemisphere, the animals received an intravenous infusion of 10, 28, 100, or 280 mM L-lactate (n = 10 for each group) for 3 h at a rate of 0.65 ml/h. Shams and control injured animals received a saline infusion. At 11-15 days post injury, cognitive deficits were examined using the Morris Water Maze (MWM) test. Three groups of rats were used for ATP analysis: shams, injured + saline infusion, and injury + the optimal lactate dose as determined by the MWM (n = 4/group). Additionally, a group receiving 280 mM L-lactate (n = 5) and one receiving a saline infusion (n = 3) were monitored for arterial blood variables and blood pressures. Findings. In the MWM test, only the 100 mM L-lactate-treated injured animals showed a significant reduction in cognitive deficits when compared to saline-treated injured animals (p ≤ 0.05). In the ATP study, injured animals without treatment had a 53{\%} reduction in ATP level in the ipsilateral cortex, while animals with 100 mM lactate treatment had a 28{\%} reduction. (p ≤ 0.05). No lactic acidosis was induced by the intravenous infusion of 280 mM L-lactate. Conclusions. This study indicates that the intravenous infusion of 100 mM L-lactate provided the optimal concentration of the substrate to ameliorate cognitive impairment, probably via the regeneration of ATP following TBI in rats.",
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