Evaluation of Homeostatic Changes in CSF Circulation: In vivo Analysis of the Effect of Neurotransmitter Accumulation in the Extracellular Space Following Transient Global Ischemia

Abstract

Accumulation of potassium and excitatory amino acids (EAA) in the extracellular space (ECS) following ischemia has been well documented. Careful monitoring of these transients is crucial to gain a better understanding of CNS pathophysiology. This study was initiated to determine if CSF concentrations of EAAs reflect those measured in the ECS. Transient global ischemia, 20 minutes in duration, was produced by clamping the left subclavian and innominate arteries combined with hemorrhagic hypotension. The accumulation of glutamate and electrolytes were measured in CSF and the extracellular fluid (ECF) of cerebral cortex. Microdialysis (MD) was utilized to measure the extracellular concentrations while direct sampling of CSF was provided via cannulation of the cisterna magna. Hydrogen clearance and laser doppler methods were used to monitor regional cortical CBF. Our results show that extracellular concentrations of potassium ([K+]ECF) and glutamate significantly increased following the initiation of ischemia (p < 0.05). The extracellular concentration of these substances decreased with the restoration of CBF. In CSF, a similar trend was observed following re-circulation (p < 0.05). However, CSF glutamate levels did not return to pre-ischemic values.