1944 was the year when Leão described for the first time an electrophysiological phenomenon of the brain cortex, which has not ceased to intrigue researchers ever since and is being implicated in migraine as well as in stroke. He called it Cortical Spreading Depression (CSD) because this massive synchronous and sustained depolarization of all cell types in a given area spreads at the rather low speed of 3 mm per minute over the cortex, temporarily depressing normal electrical activity as it is seen in EEG.
Such a wave of initial excitation followed by paralysis that spreads like a bush fire would give a very attractive explanation for the underlying process of the aura of classical migraine. During the aura somatosensory disturbances migrate over the perception sphere. And, in fact, four years before CSD was discovered, Lashley calculated speed of a supposed phenomenon in his primary visual cortex if it was the cause of the fortification figures of his own migraine aura: He calculated 3 mm per minute.
The generalized depolarization during CSD causes dramatic ionic currents. To regain ionic balance, energy dependent ion transporters of the cells have to work full speed, which means maximal stress to energy metabolism. May be this is why the wave of depolarization is followed by a wave of hyperperfusion that carries substrate and oxygen to the distressed cells. That successive CSD does not cause any irreversible damage to the tissue may indicate the success of adapted blood supply. A migraine attack does not leave any neurological deficits behind, either.
This may be all different if the perfusion of the affected cortical area is impaired in the first place: i.e. in the penumbra of an ischaemic focus. The extreme workload of ion transport may just "finish off" cells that have already been struggling, thus increasing the volume of the resulting infarction. Models of focal ischaemia have shown Periinfarct Depolarizations (PID) that resemble CSD closely and produced evidence for their influence on infarction size.
We investigate CSD in the rat. The anaesthetized animals are being ventilated and physiologically (body temperature, blood pressure and respiratory gases) monitored. CSD is elicited by topical application of KCl solution to the frontal cortex (1) in the figure). Its way over the cortex is registrated by superficial electrodes that measure the cortical DC potential (2). The ensuing blood flow response can be measured by a laser Doppler probe (3).
The new optical method of Near Infrared Spectroscopy (NIRS) relies on the specific absorption properties of oxygenated and deoxygenated haemoglobin and of the terminal enzyme in the respiratory chain: cytochrome aa3 in the infrared light range near the visual spectrum. Light in this spectral range penetrates even dense tissue as the bone very well and is attenuated only by these chromophores, which makes the method very attractive for non invasive measurements in humans. Light of several wavelengths is brought from a laser diode by fiber optics to the skull (4). In a certain distance the modulated light is collected by another fibre bundle (5) that brings it back to the machine. There it is amplified and concentration changes of the chromophores are being calculated by an integrated computer from changes in optical density. These concentration changes reflect the oxygen supply to the regional tissue.
An additional electrochemical oxygen probe measures the actual oxygen tension of the cortical tissue (6).
Our experiments demonstrated that the blood and tissue oxygenation is increased during CSD in normal tissue, which may indicate that the oxygen supply even exceeds the actual demand.
Currently we investigate PID in rats during middle cerebral artery occlusion. Our first data, in contrast to normal CSD, show a drop in blood oxygenation during the spreading depolarization. That supports the notion that PID can knock out brain tissue that may otherwise survive.