Neurocognitive Outcomes in a Cisternal Blood Injection Murine Model of Subarachnoid Hemorrhage

Nefize Turan, Robert A. Heider, Maheen Nadeem, Brandon A. Miller, Bushra Wali, Seema Yousuf, Iqbal Sayeed, Donald G. Stein, Gustavo Pradilla

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model. Methods: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus. Results: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus. Conclusions: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH.

Original languageEnglish
Article number105249
JournalJournal of Stroke and Cerebrovascular Diseases
Issue number11
StatePublished - Nov 2020

Bibliographical note

Funding Information:
Financial Support: This work was supported by the Emory Medical Care Foundation (GP), Karen M. Schurr Memorial Chair of Research (BAM) Grants by the Brain Aneurysm Foundation, the Emory University Department of Neurosurgery departmental funds (GP) and a gift in support of research to the Department of Emergency Medicine Brain Research Laboratory from Allen and Company (DGS). The funding source has no involvement in the conduct of the research and/or preparation of the article.

Publisher Copyright:
© 2020 Elsevier Inc.


  • Elevated plus maze
  • Morris Water Maze
  • inflammation
  • microglia
  • neurobehavioral tests
  • subarachnoid hemorrhage

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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