Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury

Abstract

This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MD(glc)), lactate (MD(lac)), and pyruvate (MD(pyr)), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MD(pyr) was not altered after CCI-Sal, whereas MD(lac) levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MD(glc) decreased bilaterally (p < 0.05). MD(pyr) levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MD(lac) decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MD(glc) levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI.

FIG. 1.

Mean (±SEM) arterial serum concentrations of pyruvate (A), lactate (B), and glucose (C) at baseline (Base) and from 10 to 75 min after injection of saline (-Sal) or sodium pyruvate (-SP, 1000 mg/kg) in rats with sham (Sham) or cortical contusion injury (CCI).

FIG. 2.

Mean (±SEM) extracellular changes in concentrations of pyruvate, expressed as percent of baseline (Base), measured in microdialysis samples collected every 15 min from the ipsilateral (A) or contralateral (B) cerebral cortex after injection of saline (-Sal) or sodium pyruvate (-SP, 1000 mg/kg) in rats with sham (Sham) or left cortical contusion injury (CCI).

FIG. 3.

Mean (±SEM) extracellular changes in concentrations of lactate, expressed as percent of baseline (Base), measured in microdialysis samples collected every 15 min from the ipsilateral (A) or contralateral (B) cerebral cortex after injection of saline (-Sal) or sodium pyruvate (-SP, 1000 mg/kg) in rats with sham (Sham) or left cortical contusion injury (CCI).

FIG. 4.

Mean (±SEM) extracellular changes in concentrations of glucose, expressed as percent of baseline (Base), measured in microdialysis samples collected every 15 min from the ipsilateral (A) or contralateral (B) cerebral cortex after injection of saline (-Sal) or sodium pyruvate (-SP, 1000 mg/kg) in rats with sham (Sham) or left cortical contusion injury (CCI).

FIG. 5.

Mean (±SEM) number of acid fuchsin (AF) or Fluoro-jade B (FJ) positive cells in the cortex ipsilateral and medial to cortical contusion injury (CCI) at 6 h after injection of saline (-Sal) or sodium pyruvate at a dose of 500 mg/kg (-500) or 1000 mg/kg (-1000). *p < 0.05 vs. CCI-Sal.

FIG. 6.

Tissue loss in the left/injured cortical mantle, expressed as percentage of tissue volume in the contralateral cortical mantle (mean ± SEM), at 2 weeks after cortical contusion injury (CCI) in rats with a single (5 min post-CCI) injection of saline (-Sal) or sodium pyruvate at a dose of 500 mg/kg (-500) or 1000 mg/kg (-1000), and rats with three injections (5, 65, and 125 min post-CCI) of the 1000 mg/kg dose of sodium pyruvate (-3x1000). ***p < 0.001 vs. CCI-Sal, CCI-500, or CCI-1000.