Subarachnoid hemorrhage in C57BL/6J mice increases motor stereotypies and compulsive-like behaviors

ABSTRACT

Objective

Long-term behavioral, mood, and cognitive deficits affect over 30% of patients with subarachnoid hemorrhage (SAH). The aim of the present study was to examine the neurobehavioral outcomes following endovascular perforation induced SAH in mice.

Methods

C57BL/6 J (B6) mice were exposed to endovascular perforation induced SAH or control surgery. Three weeks later, mice received a series of behavioral tests, e.g. motor function, stereotypy, learning, memory, behavioral flexibility, depression and anxiety. The immunohistologic experiment examined neuronalloss in the cortex following SAH.

Results

SAH mice exhibited increased marble burying and nestlet shredding compared to that of control mice. Although SAH did not affect memory, learning or reversal learning,mice displayed greater overall object exploration in the novel object recognition test, as well as elevated perseveration during probabilistic reversal learning.In the forced swim and open field tests, SAH mice performed comparably to that of control mice. However, SAH mice exhibited an increased frequency in ‘jumping’ behavior in the open field test. Histological analyses revealed reduced neuron density in the parietal-entorhinal cortices of SAH mice on the injured side compared to that of control mice.

Discussion

The findings suggest that parietal-entorhinal damage from SAH increases stereotyped motor behaviors and ‘compulsive-like’ behaviors without affecting cognition (learning and memory) or mood (anxiety and depression). This model can be used to better understand the neuropathophysiology following SAH that contributes to behavioral impairments in survivors with no gross sensory-motor deficits.

KEYWORDS:

• Subarachnoid hemorrhage
• neurobehavioral tests
• stereotyped motor behavior
• compulsive-like behavior
• repetitive behavior
• mice

Acknowledgments

In memoriam: Dale A. Pelligrino,PhD, age 67, passed away 15 August 2016 at his home, surrounded by the love of his family. In 1994, he became a Research Professor at the University of Illinois at Chicago, Department of Anesthesiology Research. He went on to direct his own lab and retired in 2016. He was taken too soon and will be missed dearly.

Highlights

The parietal-entorhinal cortical damage from SAH in miceleads to stereotyped motor behaviors and ‘compulsive-like’ behaviors without overall affecting cognition (learning and memory) or mood (anxiety and depression).

Disclosure statement

This work was supported by grant fromthe Department of Anesthesiology, University of Illinois at Chicago.All experiments were approved by the Institutional Laboratory Animal Care and Use Committee at the University of Illinois at Chicago.

All authors report no conflict of interest.

Additional information

Funding

This work was supported by the Department of Anesthesiology, University of Illinois at Chicago.

Notes on contributors

Danop Nanegrungsunk

Danop Nanegrungsunk Resident physician, Department of Anesthesiology, University of Illinois College of Medicine at Chicago.

Michael E. Ragozzino

Michael E. Ragozzino Professor, Department of Psychology at the University of Illinois at Chicago, Chicago, IL USA.

Hao-Liang Xu

Hao-Liang Xu Associate Professor, Neuroanesthesia Research Laboratory, University of Illinois College of Medicine, Chicago, IL. Current fellow of hematopathology, Department of Pathology and immunology, Washington University School of Medicine in St. Louis.

Kyle J. Haselton

Kyle J Haselton Medical Student, Neuroanesthesia Research Laboratory, University of Illinois College of Medicine, Chicago, IL. Current resident physician, Department of Anesthesiology, Mayo Clinic in Rochester, MN.

Chanannait Paisansathan

Chanannait Paisansathan Professor, Department of Anesthesiology, University of Illinois College of Medicine at Chicago.