BACKGROUND: Spreading depression (SD) is known to go along with temporary 
breakdown of ion gradients and cell swelling which spontaneously normalizes. 
Here, the effects of SD at reduced flow conditions as encountered in the 
ischemic penumbra are examined.
METHODS: In rats the right carotid artery was permanently occluded. MABP was 
lowered to 50 mmHg for 30 min. This is sufficient to reduce CBF to penumbra-like 
conditions in the right hemisphere. The following parameters were assessed: 
rCBF, DC potential, and tissue impedance. 5 or 15 min after onset of flow 
reduction one SD wave was initiated by microinjection of KCl. Histology was 
performed after 7 days.
RESULTS: In animals with hypotension there was depolarization resembling anoxic 
depolarization after SD induction and an uncoupling of CBF and metabolism only 
in the right hemisphere. Impedance increased with SD but did not recover 
spontaneously as long as rCBF remained reduced. 15 min of SD-induced cell 
swelling was tolerated without permanent damage, whereas 25 min were followed by 
severe neuron loss in the affected cortex after 7 days.
CONCLUSIONS: The study demonstrates the induction of penumbra conditions in the 
cortex of one hemisphere. SD is followed by cell swelling which persists as long 
as flow is critically reduced. The experiments illustrate how peri-infarct 
depolarizations may detrimentally affect the penumbra.