Introduction
Peri-infarct depolarizations may progressively injure the ischemic penumbra 1 . Other factors known to worsen conditions in the subacute stage of focal brain ischemia include brain swelling and rise of intracranial pressure (ICP), which potentially results in a malignant course of infarction 2 . We intended to investigate the relevance of steady and transitory ICP elevations in focal ischemia for the induction of peri-infarct depolarizations in subcortical regions of ischemic territories.
Methods
In 11 anesthetized cats, the left middle cerebral artery (MCA) was prepared transorbitally. Micropipette calomel electrodes inserted into the medial and lateral portion of the left caudate nucleus measured the direct current (DC) potential and the spontaneous electrical activity (EEG). Laser Doppler probes measured cortical blood flow (LDF) extradurally on ectosylvian gyrus ipsilateral to MCAO. A strain-gauge MicroSensor and a thermocouple measured subdurally intracranial pressure (ICP) and brain temperature, respectively, on the contralateral marginal gyrus. All parameters were continuously recorded before and for 24 hours following permanent MCA occlusion.
Results
In all animals, severe focal ischemia was conformed by LDF. Different types of peri-infarct depolarizations (negative DC shifts >10 mV) included terminal depolarizations (TD: without repolarization), long depolarizations (LD: repolarization after 65±48 min) and spreading depression-like depolarizations (SD: 5±1 min). In 4/11 cats, these depolarizations (n=23; 14 SDs, 4 LDs and 5 TDs) were either associated with a) gradual, long-lasting or b) with rather steep, temporary ICP elevations. Analysis of the temporal relationship between ICP and DC alterations revealed that in 22/23 cases, the starting points of ICP rises preceded those of depolarizations, although the time spans between starting points differed considerably (mean 14.9±21.4 min). Gradual, long-lasting ICP elevations were severe (542±282% of control) and resulted always in TD or LD. In 4 cases of TD, malignant infarction with transtentorial herniation developed finally. Steep, temporary ICP elevations (60±54 % of control) led in all instances to the induction of SDs
Conclusion
Our study reveals a close relationship between temporary and permanent elevations of ICP and the induction of different types of tissue depolarization including peri-infarct spreading depression and characterizes therefore a relevant process of progressively worsening conditions in the subacute stage of focal ischemia.