Cerebral ischemia comes in waves

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Science Translational Medicine  20 Sep 2017:
Vol. 9, Issue 408, eaao6127
DOI: 10.1126/scitranslmed.aao6127


Subarachnoid blood induces spreading depolarizations, which are associated with cortical infractions.

Cortical spreading depolarizations are waves of electrical silence caused by massive coordinated neuronal depolarizations that have been shown to occur in different types of acute brain injury, including subarachnoid hemorrhage (SAH). During brain injury, the presence of cortical spreading depolarizations has been associated with brain hypoxia and poor clinical outcomes; however, their causes and clinical impact in SAH are not well understood. Hartings et al. used a swine model of SAH and studied subdural electrocorticography recordings in 23 patients with aneurysmal SAH to determine causes and clinical consequences of cortical spreading depolarizations.

Fresh and clotted blood was injected into the subarachnoid space in gyrencephalic swine brains to create a model of SAH. Intracranial electrodes were placed to measure the number of cortical spreading depolarizations. Infusion of fresh blood resulted in continuous, repetitive spreading depolarizations and infusion of clotted blood caused spreading depolarizations associated with cortical infarctions. Twenty-three aneurysmal SAH patients underwent subdural electrocorticography and magnetic resonance imaging to detect spreading depolarizations and cerebral ischemia. 86% of patients with ischemic lesions had cortical spreading depolarizations compared with only 9% of those who had no lesions. The findings in the animal model in conjunction with the observation that SAH patients with early infarcts have more spreading depolarizations suggest that spreading depolarizations might contribute to cerebral ischemia in SAH.

The main limitation of the study is that although SAH was shown to lead to cortical spreading depolarizations and ischemic injury, the mediators of this injury were not investigated thoroughly. Cortical spreading depolarizations occur after acute brain injuries of different types. A better understanding of the mechanisms underlying the relationship between cortical spreading depolarization and ischemic processes is needed to develop targeted interventions for preventing ischemic damage.

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