Does Leão’s Spreading Depression Cause Irreversible Brain Damage?
It has been repeatedly suggested that the cell damage in infarction of myocardium and of brain tissue is the result of intracellular accumulation of calcium. In agreement with this hypothesis we found earlier that recovery of synaptic transmission in hippocampal tissue slices following transient oxygen withdrawal is inversely related to the duration of hypoxic depolarization1. Calcium enters cells not only during hypoxic depolarization but also during Leão’s spreading depression (LD). We now asked whether LD in well oxygenated hippocampal slices has aftereffects similar to those of transient hypoxia. Slices were maintained in an interface chamber at about 36°C in artificial cerebrospinal fluid (ACSF) that contained 1.2 mM Ca2+, 1.2 mM Mg2+, 3.5 mM K+ and was flowing at 2 ml/min. Interstitial potassium ([K+] 0 ) and extracellular potentials evoked by stimulation of the Schaffer collateral-commisural fibers were recorded in st. radiatum and st. pyramidale of CA1 with ion selective microelectrodes. LD was provoked by high-[K+] ACSF (133 mM K+, 0 mM Na+) flowing from tubing positioned over the slice, at 0.6 ml/min, for periods ranging from 10 sec to several min. High [K+] exposure in excess of 25 sec reliably provoked LD, recognized by a sudden negative shift of extracellular potential and elevation of [K+ 0 above 20 mM. Potential and [K+] 0 returned to control levels after a variable time following cessation of high [K+] application. Delayed recovery of [K+] 0 may be due to impaired active membrane transport. LD duration was defined as the time from onset of [K+] 0 elevation until 1/2 decay (return to 50% of maximal level).