Introduction: Comprehensive clinical data revealed that spreading depolarization (SD) plays a central role in developing cortical lesions in patients with acute brain injury. Detailed mapping of the brain’s electrical activity in clinics at the onset of focal ischemic stroke and during the initial phase of cortical injury development is lacking because electroencephalography (ECoG) monitoring typically starts hours or days after focal ischemia. Non-human primate (NHP) models are considered the best representation of human stroke due to their genetic, physiological, and anatomical similarities to humans.
Methods: Craniotomies were performed over the left and right hemispheres on five male and female nemestrina and rhesus macaques aged 23-32 years. Subdural electrode arrays were placed bilaterally over the middle cerebral artery (MCA) territory, recording from 24 electrodes 1 cm apart on the left cortex and 7 electrodes on the right. After 30 minutes of baseline ECoG, the left MCA and, in some cases, also the left internal carotid or anterior cerebral arteries were permanently occluded with aneurysmal clips. Repetitive SDs were recorded during the next 3 hours, followed by terminal SD during euthanization.
Results: No epileptiform activity was noted in any of the five animals. Non-spreading electrical silence developed in the ischemic core within seconds of ischemic onset, followed by SD and SD-initiated negative ultraslow potential (NUP) with a substantial delay. These events defined the ischemic core and led to histologically confirmed cell damage. The initial and subsequent transient SDs caused the spreading depression of spontaneous activity at the normally perfused surrounding cortex without any signs of histological damage.
Conclusion : Circulatory arrest at the end of experiments first induced non-spreading depression of activity followed by SD and eventually, the SD-initiated NUP, which indicated brain death. Results in gyrencephalic NHP hold significant implications for understanding the causal role of SD in acute brain injury development alongside the SD continuum as it transitions from persistent depolarization in the severely ischemic cortex to transient depolarization in the normal brain
.jpg)
