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.

The Neuroprotective Effect of Lactate Is Not Due to Improved Glutamate Uptake after Controlled Cortical Impact in Rats

“…Our glutamate microdialysis levels changed briefly to elevated levels similar to those reported by Palmer and colleagues (Palmer et al, 1993). If the trauma is more severe, more pronounced and prolonged glutamate and lactate release occurs (Fukushima et al, 2009;Palmer et al, 1993;Rose et al, 2002). In a model of focal ischemia, reperfusion seems to further elevate and extend glutamate and lactate release (Lin et al, 2002), making an effect of 4-CIN more likely.…”

Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology

“…injection of 500 mg/kg of pyruvate. The rationale for the chosen dose comes from evidence indicating that at this concentration, given the first pass partial drug metabolization by the liver, there is still significant pyruvate permeation across the blood-brain barrier (Miller and Oldendorf, 1986), thereby allowing the building up of significant levels of pyruvate in the brain (Fukushima et al, 2009). Furthermore, 500 mg/kg of pyruvate has been successfully employed in previous studies aiming at promoting neuroprotection in rat models of epilepsy or diabetes (Suh et al, 2005;Kim et al, 2007).…”

Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat

“…), at 1, 12 and 24 h post-CCI. The SP dose was chosen based on prior data indicating this dose was optimal compared to SP at 500 mg/kg after CCI (Fukushima et al, 2009). EP treatment was administered at two dosages (20 mg/kg or 40 mg/kg, i.p.…”

“…We have previously reported a neuroprotective role of sodium pyruvate (SP) treatment in a rat model of cortical contusion injury (CCI) (Fukushima et al, 2009). In those studies a single SP injection (1000 mg/kg, i.p.)…”