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Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats

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Abstract

Background

Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive deficits in the context of similar levels of insult severity in the cisterna magna double-blood (DB) injection versus prechiasmatic blood (PB) injection SAH models.

Methods

Pilot work identified blood injectate volumes necessary to provide similar mortality rates (20–25 %). Rats were then randomly assigned to DB or PB insults. Saline injection and naïve rats were used as controls. Functional and cognitive outcome was assessed over 35 days.

Results

DB and PB caused similar transient rotarod deficits. PB rats exhibited decreased anxiety behavior on the elevated plus maze, while anxiety was increased in DB. DB and PB caused differential deficits in the novel object recognition and novel object location tasks. Morris water maze performance was similarly altered in both models (decreased escape latency and increased swimming speed). SAH caused histologic damage in the medial prefrontal cortex, perirhinal cortex, and hippocampal CA1, although severity of injury in the respective regions differed between DB and PB.

Conclusion

Both SAH models caused long-term cognitive deficits in the context of similar insult severity. Cognitive deficits differed between the two models, as did distribution of histologic injury. Each model offers unique properties and both models may be useful for study of SAH-induced cognitive deficits.

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Funding

This research was funded by the Department of Anesthesiology, Duke University Medical Center.

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Author notes

    Authors and Affiliations

    1. Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA

      Toshihiro Sasaki, Ulrike Hoffmann, Motomu Kobayashi, Huaxin Sheng, Frederick W. Lombard & David S. Warner

    2. Department of Pharmacy, University of Sunderland, Wharncliffe Street, Sunderland, SR1 3SD, UK

      Abdelkader Ennaceur

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    1. Toshihiro Sasaki
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    2. Ulrike Hoffmann
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    3. Motomu Kobayashi
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    Correspondence to David S. Warner.

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    All applicable institutional and/or national guidelines for the care and use of animals were followed.

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    Toshihiro Sasaki and Ulrike Hoffmann have contributed equally to this manuscript.

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    Sasaki, T., Hoffmann, U., Kobayashi, M. et al. Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats. Neurocrit Care 25, 293–305 (2016). https://doi.org/10.1007/s12028-016-0250-1

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    • DOI: https://doi.org/10.1007/s12028-016-0250-1

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