Spreading depression induces permanent cell swelling under penumbra conditions

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.

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.

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.

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.