Calcium ion transients in peri-infarct depolarizations may deteriorate ion homeostasis and expand infarction in focal cerebral ischemia in cats.
OBJECTIVE
Harmful effects of peri-infarct depolarizations (PIDs) may depend on recurrent Ca(2+) influx. Thus far, few studies have documented the relevance of PIDs in gyrencephalic animals, and the progressive nature of this process has not been investigated over extended periods. We therefore studied in prolonged focal ischemia in cats spatial and temporal profiles of extracellular calcium ([Ca(2+)](o)) shifts in relation to direct current (DC) potential, nitric oxide (NO) concentration and regional cerebral blood flow alterations, and final pathological outcome.


METHODS
In halothane-anesthetized cats receiving either vehicle (n=12) or MK-801 treatment (5 mg/kg IV; n=10), the left middle cerebral artery was permanently occluded. Laser-Doppler probes, ion-selective microelectrodes, and NO electrodes measured simultaneously regional cerebral blood flow, DC potential, electrocorticogram, [Ca(2+)](o), and NO concentrations in ectosylvian and suprasylvian gyri of the left cerebral cortex.


RESULTS
Persistent depolarization immediately after middle cerebral artery occlusion occurred in 10 ectosylvian and 4 suprasylvian gyri of vehicle-treated animals and in 9 ectosylvian and 3 suprasylvian gyri of MK-801-treated animals. PIDs associated with transient decreases of [Ca(2+)](o) were detected in suprasylvian gyri of only 4 vehicle-treated animals, of which 3 developed recurrent PIDs. Electrocorticogram was suppressed during PIDs, and electrocorticogram recovery worsened in a stepwise manner with consecutive depolarizations. PID duration increased slightly with ongoing ischemia and evolved to persistent depolarization at a final stage. NO transients were not detected during PID, and regional cerebral blood flow transients were not pronounced. Infarction was larger with initial persistent depolarization than with PID and was smallest in MK-801-treated animals.


CONCLUSIONS
PID is not a common finding in peri-infarct zones in cats, and it is suppressed by the N:-methyl-D-aspartate antagonist MK-801. However, if repeated PIDs are generated, they result in a stepwise, progressive breakdown of neuronal function and ion homeostasis, probably contributing to the growth of infarction in focal cerebral ischemia. Recurrent Ca(2+) influx is a mechanism that presumably contributes to this process.
Ohta
K
K
Max-Planck-Institut für neurologische Forschung, Cologne, Germany.
Graf
R
R
Rosner
G
G
Heiss
W D
WD
D000818:Animals; D001783:Blood Flow Velocity; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002415:Cats; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography; D005260:Female; D006706:Homeostasis; D020244:Infarction, Middle Cerebral Artery; D017136:Ion Transport; D017078:Laser-Doppler Flowmetry; D008297:Male; D008564:Membrane Potentials; D008839:Microelectrodes; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism
D018696:Neuroprotective Agents; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D002118:Calcium