THE INFLUENCE OF REPEATED SPREADING DEPRESSION-INDUCED CALCIUM TRANSIENTS ON NEURONAL VIABILITY IN MODERATELY HYPOGLYCEMIC RATS

The calcium transients which are associated with spreading depression (SD) do not lead to neuronal necrosis, even if the SDs are repeated ov er hours. We have previously shown that a restriction of energy produc tion by moderate hypoglycemia prolongs the calcium transients during S D, In the present experiments, we explored whether such prolonged tran sients lead to neuronal necrosis. To that end, SDs were elicited for 2 h by topical application of KCl in anesthetized rats at plasma glucose concentrations of 6, 3, and 2 mM. The animals were then allowed to re cover, and they were studied histopathologically after 7 days. In two other groups, hypoglycemic coma of 5 min duration (defined in terms of the d.c. potential shift) was induced either without or with a preced ing train of SDs. These animals were also evaluated with respect to hi stopathological alterations. SDs elicited for 2 h did not give rise to neuronal damage when elicited at plasma glucose concentration of 6 mM , and, of the animals maintained at 3 and 2 mM, only a few animals sho wed (mild) damage. In general, therefore, repeated SDs with calcium tr ansients of normal or increased duration fail to induce neuronal damag e. The results suggest that, if calcium transients are responsible for a gradual extension of the infarct into the penumbra zone of a focal ischemic lesion some additional pathophysiological factors must be pre sent, such as overt energy failure, acidosis, or microvascular damage. A hypoglycemia-induced calcium transient of 5 min duration gave no or only moderate neuronal damage. However, if a series of SDs were elici ted in the precoma period, the damage was exaggerated. The results dem onstrate that, normally, brain tissues can tolerate a hypoglycemic cal cium transient of up to 5 min duration without incurring neuronal necr osis. They also demonstrate that calcium transients preceding a subseq uent insult involving calcium influx into cells exaggerate the damage incurred. It is tentatively concluded that the ''priming'' transients alter membrane properties in such a way that cellular calcium homeosta sis is perturbed.