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 language | English |
|---|---|
| Pages (from-to) | 919-927 |
| Number of pages | 9 |
| Journal | Acta Neurochirurgica |
| Volume | 149 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2007 |
| Externally published | Yes |
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Keywords
- ATP
- Cognitive deficits
- L-lactate
- TBI
ASJC Scopus subject areas
- Clinical Neurology
- Surgery
Cite this
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 journal › Article
}
TY - JOUR
T1 - Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat
AU - Holloway, R.
AU - Zhou, Z.
AU - Harvey, H. B.
AU - Levasseur, J. E.
AU - Rice, A. C.
AU - Sun, D.
AU - Hamm, R. J.
AU - Bullock, Ross
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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.
AB - 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.
KW - ATP
KW - Cognitive deficits
KW - L-lactate
KW - TBI
UR - http://www.scopus.com/inward/record.url?scp=34548225552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548225552&partnerID=8YFLogxK
U2 - 10.1007/s00701-007-1241-y
DO - 10.1007/s00701-007-1241-y
M3 - Article
VL - 149
SP - 919
EP - 927
JO - Scientific Computing and Instrumentation
JF - Scientific Computing and Instrumentation
SN - 1078-8956
IS - 9
ER -