Responses to Cortical Spreading Depression under Oxygen Deficiency.

J Sonn

doi:10.2174/1874205x01206010006

Abstract

Objectives:Objectives: The effect of cortical spreading depression (CSD) on extracellular K+ concentrations ([K+]e), cerebral blood flow (CBF), mitochondrial NADH redox state and direct current (DC) potential was studied during normoxia and three pathological conditions: hypoxia, after NOS inhibition by L-NAME and partial ischemia.Methods:A special device (MPA) was used for monitoring CSD wave propagation, containing: mitochondrial NADH redox state and reflected light, by a fluorometry technique; DC potential by Ag/AgCl electrodes; CBF by laser Doppler flowmetry; and [K+]e by a mini-electrode.Results and Discussion:CSD under the 3 pathological conditions caused an initial increase in NADH and a further decrease in CBF during the first phase of CSD, indicating an imbalance between oxygen supply and demand as a result of the increase in oxygen requirements. The hyperperfusion phase in CBF was significantly reduced during hypoxia and ischemia showing a further decline in oxygen supply during CSD. CSD wave duration increased during the pathological conditions, showing a disturbance in energy production.Extracellular K+ levels during CSD, increased to identical levels during normoxia and during the three pathological groups, indicating correspondingly increase in oxygen demand. 5. The special design of the MPA enabled identifying differences in the simultaneous responses of the measured parameters, which may indicate changes in the interrelation between oxygen demand, oxygen supply and oxygen balance during CSD propagation, under the conditions tested. 6. In conclusion, brain oxygenation was found to be a critical factor in the responses of the brain to CSD.

Highlights

Cortical spreading depression (CSD) is a transient neuronal depolarization that is accompanied by a negative shift in the direct current (DC) potential and a flattening in EEG [1], changes in membrane permeability as well as in the ionic homeostasis [2], thereby increasing energy consumption [3] and blood flow [4, 5]
The hyperperfusion phase in cerebral blood flow (CBF) was significantly reduced during hypoxia and ischemia showing a further decline in oxygen supply during CSD. 3
Arterial blood samples were taken during normoxia and hypoxia

Summary

Introduction

Cortical spreading depression (CSD) is a transient neuronal depolarization that is accompanied by a negative shift in the DC potential and a flattening in EEG [1], changes in membrane permeability as well as in the ionic homeostasis [2], thereby increasing energy consumption [3] and blood flow [4, 5]. The responses of the brain to CSD were used as a tool that increases oxygen demand [7] and serves as an indicator to the tissue energetic-metabolic state [7,8,9]. In the case of healthy normoxic brain, repeated CSD waves do not cause any damage to the tissue [10]. The brain is completely dependent upon a continuous supply of blood flow providing oxygen, glucose, nutrients etc. During pathological conditions, where oxygen supply is limited, such as hypoxia or ischemia, any increase in oxygen demand will cause an oxygen deficiency that will end with severe functional disorders and irreversible brain

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Conclusion