Neuro-Electronics Research Flanders

NERF SEMINAR: Spreading depolarization in the brain of rats and humans

Speaker: Ana Ferreira
Time: Wednesday, May 23, 2018, 11:00 am
Location: Imec Tower room 1.B
Registration: Please register here if you are an external participant.

Spreading depolarization is the generic term for depolarization waves in the central nervous system characterized by abrupt, near-complete sustained depolarization of neurons, observed as a large change of the slow electrical field potential. In the clinic, unequivocal electrophysiological evidence now exists that the full spectrum of spreading depolarizations occurs in patients with aneurysmal subarachnoid hemorrhage, malignant hemispheric stroke, traumatic brain injury and cardiac arrest. Spreading depolarizations in isoelectric tissue were associated with worse patient outcome. Experimental data suggests that spreading depolarizations facilitate neuronal death.

Most animal models of focal ischemia are designed to replicate severe sudden onset ischemia in humans which, e.g., occurs with embolic or thrombotic occlusion of a large vessel. In contrast, the endothelin-1 (ET-1) model allows us to induce a gradually developing milder focal ischemia by titrating the constrictive effect of different concentrations of ET-1 on the vasculature.

Gradual development of focal ischemia also occurs in the human brain, e.g. in patients with aneurysmal subarachnoid hemorrhage or in vasculitides. Previous findings suggested that the electrophysiological signature of spreading depolarizations in the ET-1 model in rat neocortex is similar to that in patients with aneurysmal subarachnoid hemorrhage.

Notably, not all neuroanatomical structures show the same vulnerability under hypoxic/ischemic stress. High vulnerability is found in cerebellar Purkinje cells, CA1 pyramidal cells of the hippocampus, layers III, IV and V neocortical pyramids and cells in the striatum. All these structures are very prone to spreading depolarizations apart from the cerebellum. The cerebellum is assumed to show spreading depolarization only under conditioning media that increase neuronal excitability. In this study we compared the electrophysiological signature of spreading depolarization between cerebral neocortex and cerebellum.