Considerable evidence from clinical studies has shown that outcomes after stroke are strongly influenced by psychosocial factors. Patients with high levels of social support or large social networks exhibit more rapid and extensive functional recovery after stroke than socially isolated individuals. In contrast, perceived social isolation predicts morbidity and mortality from cerebrovascular disease. These same effects can be reproducibly demonstrated in animals;social interaction improves behavioral deficits and reduces histological damage after experimental stroke, whereas social isolation enhances ischemic damage. The mechanisms that mediate the interactions between the social environment, behavioral responses, and disease outcomes remain unclear. Advancing age is associated with an increased risk for the development of many chronic diseases including cerebrovascular disease. With our aging population, the incidence and prevalence of stroke will continue to rise, leading to increasing numbers of stroke survivors in our communities. Many older individuals are exposed to significant psychosocial stress and isolation (loss of spouse, depression, frailty etc.), however no studies have investigated the mechanisms by which psychosocial factors influence behavioral and outcomes in aged animals. We will utilize a transient focal ischemia model in socially isolated and pair housed males. We will examine the contribution of aging to the detrimental effects of isolation on the amount of stroke damage, the immune response, and behavioral recovery. Components of the peripheral and central immune system will be examined and manipulated.

Public Health Relevance

Stroke is now the leading cause of disability in the United States. Social isolation predicts morbidity and mortality from cerebrovascular disease. The mechanisms that mediate the interactions between the social environment, behavioral responses, and disease outcomes will be studied in a rodent model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS077769-04
Application #
8715871
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Ferrell, Courtney
Project Start
2011-07-01
Project End
2015-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Verma, Rajkumar; Harris, Nia M; Friedler, Brett D et al. (2016) Reversal of the Detrimental Effects of Post-Stroke Social Isolation by Pair-Housing is Mediated by Activation of BDNF-MAPK/ERK in Aged Mice. Sci Rep 6:25176
Ritzel, Rodney M; Crapser, Joshua; Patel, Anita R et al. (2016) Age-Associated Resident Memory CD8 T Cells in the Central Nervous System Are Primed To Potentiate Inflammation after Ischemic Brain Injury. J Immunol 196:3318-30
Harris, Nia M; Ritzel, Rodney; Mancini, Nikolas et al. (2016) Nano-particle delivery of brain derived neurotrophic factor after focal cerebral ischemia reduces tissue injury and enhances behavioral recovery. Pharmacol Biochem Behav 150-151:48-56
Venna, Venugopal Reddy; McCullough, Louise D (2015) Role of social factors on cell death, cerebral plasticity and recovery after stroke. Metab Brain Dis 30:497-506
Friedler, Brett; Crapser, Joshua; McCullough, Louise (2015) One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition. Acta Neuropathol 129:493-509
Aron, Abraham W; Staff, Ilene; Fortunato, Gilbert et al. (2015) Prestroke living situation and depression contribute to initial stroke severity and stroke recovery. J Stroke Cerebrovasc Dis 24:492-9
Doran, Sarah J; Trammel, Cassandra; Benashaski, Sharon E et al. (2015) Ultrasonic vocalization changes and FOXP2 expression after experimental stroke. Behav Brain Res 283:154-61
Venna, Venugopal Reddy; Verma, Rajkumar; O'Keefe, Lena M et al. (2014) Inhibition of mitochondrial p53 abolishes the detrimental effects of social isolation on ischemic brain injury. Stroke 45:3101-4
Verma, Rajkumar; Friedler, Brett D; Harris, Nia M et al. (2014) Pair housing reverses post-stroke depressive behavior in mice. Behav Brain Res 269:155-63
Bushnell, Cheryl; McCullough, Louise (2014) Stroke prevention in women: synopsis of the 2014 American Heart Association/American Stroke Association guideline. Ann Intern Med 160:853-7

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