Background and Goals of Study: Subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. Glutamate scavengers have been shown to decrease glutamate concentrations in the blood and improve neurological outcome following ischemic stroke and traumatic brain injury in rats.
This study examines the value of blood glutamate scavengers, pyruvate and oxaloacetate, as a therapeutic neuroprotective strategy in a rat model of SAH. We additionally investigated whether glutamate scavenging was the mechanism responsible for any resulting neuroprotection.
Materials and Methods: SAH was induced in 60 rats by autologous arterial blood injection into the cisterna magnum. 20 additional rats served as the sham group, with a 0.3 ml saline injection into the cisterna magnum. 60 minutes later, rats were treated with isotonic saline, 250 mg/kg oxaloacetate, or 125 mg/kg pyruvate by intravenous infusion for 30 minutes at a rate of 0.1 ml/100g/min. Prior to the induction of SAH (baseline) and 90 minutes after SAH, blood samples were collected. Rats' neurological status was measured 24 hours following SAH. Glutamate concentrations in the CSF of half of the rats were also measured 24 hours following SAH. The blood brain barrier (BBB) permeability in the parieto-occipital and frontal lobes was assessed in the remaining half via histological analysis 48 hours following SAH.
Results and Discussion: Blood glutamate levels were decreased in rats treated with pyruvate or oxaloacetate at 90 minutes following SAH (p < 0.001). CSF glutamate was decreased in rats treated with pyruvate (p< 0.05). Neurological performance improved significantly in rats treated with pyruvate (p< 0.01) or oxaloacetate (p< 0.05). There was less BBB breakdown in the parieto-occipital lobes in rats treated with oxaloacetate (p< 0.01) or pyruvate (p< 0.01), and in the frontal lobe in rats treated with pyruvate (p< 0.05).
Conclusions: This study suggests the effectiveness of blood glutamate scavengers, pyruvate and oxaloacetate, in the treatment of SAH in rats. The data suggests that the observed neuroprotection with treatment of pyruvate or oxaloacetate is mediated via their blood glutamate scavenging effect.
Acknowledgements: This work was supported by the grant awarded to Alexander Zlotnik MD, PhD from the European Society of Anesthesiologists in 2010.