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 over hours. We have previously shown that a restriction of energy production by moderate hypoglycemia prolongs the calcium transients during SD. In the present experiments, we explored whether such prolonged transients 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 recover, 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 preceding train of SDs. These animals were also evaluated with respect to histopathological 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 showed (mild) damage. In general, therefore, repeated SDs with calcium transients of normal or increased duration fail to induce neuronal damage. 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 present, 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 elicited in the precoma period, the damage was exaggerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Gidö
G
G
Laboratory for Experimental Brain Research, University Hospital, Lund, Sweden.
Kristián
T
T
Katsura
K
K
Siesjö
B K
BK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004569:Electroencephalography; D004594:Electrophysiology; D007003:Hypoglycemia / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D015220:Calcium Channels; D007328:Insulin; D011189:Potassium Chloride