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Am J Phys Med Rehabil. 2018 Jul;97(7):492-499. doi: 10.1097/PHM.0000000000000904.

Impaired Cognitive Performance in Endothelial Nitric Oxide Synthase Knockout Mice After Ischemic Stroke: A Pilot Study.

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From the Stroke Biological Recovery Laboratory, Spaulding Rehabilitation Hospital, The teaching affiliate of Harvard Medical School, Charlestown, Massachusetts (SL, YW, ZJ, YH, QMW); Guangdong Pharmaceutical University, Basic Medical College, Guangzhou, China (SL); Department of Rehabilitation Medicine, Nan'ao People's Hospital of Shenzhen, The First Affiliated Hospital, Shenzhen University, Shenzhen, China (YW); The Second School of Clinical Medicine, Southern Medicine University, Guangdong, Guanzhou, China (YW); Fourth Affiliated Hospital, Zhengzhou University, Zhengzhou, China (ZJ); Department of Rehabilitation Medicine, Hebei General Hospital, Shijiazhuang, China (YH); Section of Cardiology, University of Chicago Medicine, Illinois (JKL); School of Nursing, Fatigue Research Laboratory, MGH Institute of Health Professions, Charlestown, Massachusetts (KAL, LJW); and Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (RZ).



Cognitive dysfunction and dementia are common following ischemic stroke. Endothelial nitric oxide synthase (eNOS) has been found to play an important role in neurologic function and cognition. The purpose of the present study was to assess the specific role of eNOS in cognitive performance after stroke.


Male wild-type and mice lacking eNOS (eNOS) underwent middle cerebral artery occlusion or sham-surgery. Primary outcomes were repeated measures of neurologic score, limb asymmetry, sensory/motor function, and spatial memory/learning assessed at intervals up to 28 days postsurgery. Group differences in brain microglia activation and infiltration and levels of interferon-gamma were examined.


There was no genotype × surgery interaction effect on the pattern of change in neurologic score, limb asymmetry, or sensory motor function across the 28 days postsurgery. In the Morris water maze, eNOS-/- middle cerebral artery occlusion mice displayed learning and memory deficits not evident in wild-type middle cerebral artery occlusion mice. Poorer spatial memory and learning in eNOS-/- middle cerebral artery occlusion mice was associated with a reduction in the number of activated microglia in the striatum on the lesion side and decreased brain tissue levels of interferon-gamma.


This study's data support a role for eNOS in cognitive performance after stroke. This finding may lead to the development of novel interventions to treat poststroke cognitive deficits.

[Indexed for MEDLINE]
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