Cortical Spreading Depolarizations in a Mouse Model of Subarachnoid Hemorrhage

James H Lai; Tao Qin; Sava Sakadžić; Cenk Ayata; David Y Chung

doi:10.1007/s12028-021-01397-9

Cortical Spreading Depolarizations in a Mouse Model of Subarachnoid Hemorrhage

Neurocrit Care. 2022 Jun;37(Suppl 1):123-132. doi: 10.1007/s12028-021-01397-9. Epub 2022 Jan 3.

Authors

James H Lai^{1

2}, Tao Qin¹, Sava Sakadžić³, Cenk Ayata^{1

4}, David Y Chung^{5

6}

Affiliations

¹ Neurovascular Research Unit, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th St, Charlestown, MA, 02129, USA.
² Division of Neurocritical Care, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
³ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
⁴ Stroke Service, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Neurovascular Research Unit, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th St, Charlestown, MA, 02129, USA. dychung@mgh.harvard.edu.
⁶ Division of Neurocritical Care, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. dychung@mgh.harvard.edu.

Abstract

Background: Cortical spreading depolarizations (CSDs) are associated with worse outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). Animal models are required to assess whether CSDs can worsen outcomes or are an epiphenomenon; however, little is known about the presence of CSDs in existing animal models. Therefore, we designed a study to determine whether CSDs occur in a mouse model of SAH.

Methods: A total of 36 mice were included in the study. We used the anterior prechiasmatic injection model of SAH under isoflurane anesthesia. A needle was inserted through the mouse olfactory bulb with the point terminating at the base of the skull, and arterial blood or saline (100 µl) was injected over 10 s. Changes in cerebral blood volume over the entire dorsal cortical surface were assessed with optical intrinsic signal imaging for 5 min following needle insertion.

Results: CSDs occurred in 100% of mice in the hemisphere ipsilateral to olfactory bulb needle insertion (CSD1). Saline-injected mice had 100% survival (n = 10). Blood-injected mice had 88% survival (n = 23 of 26). A second, delayed, CSD ipsilateral to CSD1 occurred in 31% of blood-injected mice. An increase in the time interval between CSD1 and blood injection was associated with the occurrence of a second CSD in blood-injected mice (mean intervals 26.4 vs. 72.7 s, p < 0.0001, n = 18 and 8). We observed one blood-injected animal with a second CSD in the contralateral hemisphere and observed terminal CSDs in mice that died following SAH injection.

Conclusions: The prechiasmatic injection model of SAH includes CSDs that occur at the time of needle insertion. The occurrence of subsequent CSDs depends on the timing between CSD1 and blood injection. The mouse prechiasmatic injection model could be considered an SAH plus CSD model of the disease. Further work is needed to determine the effect of multiple CSDs on outcomes following SAH.

Keywords: Brain aneurysm; Cortical spreading depression; Delayed cerebral ischemia; Mouse model; Neurocritical care.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cerebral Cortex
Cerebrovascular Circulation
Cortical Spreading Depression*
Disease Models, Animal
Mice
Subarachnoid Hemorrhage* / complications

Abstract

Publication types

MeSH terms

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