Skip to main content

Role of social factors on cell death, cerebral plasticity and recovery after stroke

Metabolic Brain Disease volume 30, pages 497–506 (2015)Cite this article

Abstract

Stroke is a serious global health care problem. It is now is the fourth leading cause of death and the primary cause of adult disability in the United States. Substantial evidence from both experimental and clinical studies has demonstrated that social isolation (SI) can increase stroke incidence and impair recovery. Epidemiological studies demonstrate that an increasing number of patients are living alone, and as the aging population increases, loneliness will only increase in prevalence. SI is increasingly identified as an independent risk factor for all-cause mortality. In contrast, individuals with high levels of social support exhibit more rapid and extensive functional and cognitive recovery after a wide variety of pathological insults, including stroke. Clinical data suggests that SI is an important risk factor for increased mortality and delayed functional recovery following ischemic stroke. Attesting to the importance of mortality and behavioral factors in stroke outcome is that these same effects can be reproduced in animal models of experimental stroke. This has allowed researchers to identify several mechanistic changes that occur with affiliative interactions. These include decreased systemic inflammation, elaboration of growth factors including brain derived neurotropic factor (BDNF), enhanced neurogenesis, and improved neuroimmune responsiveness in group housed animals. These may mediate the beneficial effects of social interaction on improving stroke recovery and reducing neuronal death. In this review we provide an overview of the effects of SI on ischemic injury and recovery and discuss their clinical and therapeutic implications.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

£ 29.95

Price includes VAT (United Kingdom)
Tax calculation will be finalised during checkout.

Fig. 1

References

  • Appelros P, Nydevik I, Viitanen M (2003) Poor outcome after first-ever stroke: predictors for death, dependency, and recurrent stroke within the first year. Stroke J Cereb Circ 34:122–126

    Article  Google Scholar 

  • Arndt SS, Laarakker MC, van Lith HA, van der Staay FJ, Gieling E, Salomons AR, van’t Klooster J, Ohl F (2009) Individual housing of mice–impact on behaviour and stress responses. Physiol Behav 97:385–393

    Article  CAS  PubMed  Google Scholar 

  • Avendano M, Kawachi I, Van Lenthe F, Boshuizen HC, Mackenbach JP, Van den Bos GA, Fay ME, Berkman LF (2006) Socioeconomic status and stroke incidence in the US elderly: the role of risk factors in the EPESE study. Stroke J Cereb Circ 37:1368–1373

    Article  Google Scholar 

  • Bartolomucci A, Palanza P, Sacerdote P, Ceresini G, Chirieleison A, Panerai AE, Parmigiani S (2003) Individual housing induces altered immuno-endocrine responses to psychological stress in male mice. Psychoneuroendocrinology 28:540–558

    Article  CAS  PubMed  Google Scholar 

  • Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, Czajkowski SM, DeBusk R, Hosking J, Jaffe A, Kaufmann PG, Mitchell P, Norman J, Powell LH, Raczynski JM, Schneiderman N, Enhancing Recovery in Coronary Heart Disease Patients, I. (2003) Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 289:3106–3116

    Article  PubMed  Google Scholar 

  • Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868

    Article  CAS  PubMed  Google Scholar 

  • Boden-Albala B, Litwak E, Elkind MS, Rundek T, Sacco RL (2005) Social isolation and outcomes post stroke. Neurology 64:1888–1892

    Article  CAS  PubMed  Google Scholar 

  • Bodenant M, Leys D, Debette S, Cordonnier C, Dumont F, Henon H, Girot M, Lucas C, Devos D, Defebvre L, Deplanque D, Leclerc X, Bordet R (2010) Intravenous thrombolysis for acute cerebral ischaemia: comparison of outcomes between patients treated at working versus nonworking hours. Cerebrovasc Dis 30:148–156

    Article  PubMed  Google Scholar 

  • Bondar NP, Kudriavtseva NN (2005) Impaired social recognition in male mice with repeated experience of aggression. Zh Vyssh Nerv Deiat Im I P Pavlova 55:378–384

    CAS  PubMed  Google Scholar 

  • Burton CR (2000) Living with stroke: a phenomenological study. J Adv Nurs 32:301–309

    Article  CAS  PubMed  Google Scholar 

  • Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, Howard VJ, Lichtman JH, Lisabeth LD, Pina IL, Reeves MJ, Rexrode KM, Saposnik G, Singh V, Towfighi A, Vaccarino, V, Walters MR, on behalf of the American Heart Association Stroke Council, C.o.C., Stroke Nursing, C.o.C.C.C.o.E., Prevention & Council for High Blood Pressure, R. (2014) Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. doi:10.1161/01.str.0000442009.06663.48

  • Cacioppo JT, Hawkley LC (2009) Perceived social isolation and cognition. Trends Cogn Sci 13:447–454

    Article  PubMed Central  PubMed  Google Scholar 

  • Cacioppo JT, Fowler JH, Christakis NA (2009) Alone in the crowd: the structure and spread of loneliness in a large social network. J Pers Soc Psychol 97:977–991

    Article  PubMed Central  PubMed  Google Scholar 

  • Cacioppo JT, Hawkley LC, Norman GJ, Berntson GG (2011) Social isolation. Ann N Y Acad Sci 1231:17–22

    Article  PubMed Central  PubMed  Google Scholar 

  • Cheng E, Vickrey B (2006) Is there a relationship between prestroke social isolation and outcomes following stroke? Nature clinical practice. Neurology 2:16–17

    PubMed  Google Scholar 

  • Christakis NA, Fowler JH (2007) The spread of obesity in a large social network over 32 years. N Engl J Med 357:370–379

    Article  CAS  PubMed  Google Scholar 

  • Christakis NA, Fowler JH (2013) Social contagion theory: examining dynamic social networks and human behavior. Stat Med 32:556–577

    Article  PubMed  Google Scholar 

  • Clark CJ, Guo H, Lunos S, Aggarwal NT, Beck T, Evans DA, Mendes de Leon C, Everson-Rose SA (2011) Neighborhood cohesion is associated with reduced risk of stroke mortality. Stroke J Cereb Circ 42:1212–1217

    Article  Google Scholar 

  • Craft TK, Glasper ER, McCullough L, Zhang N, Sugo N, Otsuka T, Hurn PD, DeVries AC (2005) Social interaction improves experimental stroke outcome. Stroke J Cereb Circ 36:2006–2011

    Article  Google Scholar 

  • DeVries AC, Joh HD, Bernard O, Hattori K, Hurn PD, Traystman RJ, Alkayed NJ (2001) Social stress exacerbates stroke outcome by suppressing Bcl-2 expression. Proc Natl Acad Sci U S A 98:11824–11828

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • DeVries AC, Craft TK, Glasper ER, Neigh GN, Alexander JK (2007) 2006 Curt P. Richter award winner: Social influences on stress responses and health. Psychoneuroendocrinology 32:587–603

    Article  PubMed  Google Scholar 

  • Drage MG, Heinrichs SC (2005) Phenotyping the untouchables: environmental enhancement of behavioral and physiological activation in seizure-prone El mice. Epilepsy Behav 6:35–42

    Article  PubMed  Google Scholar 

  • Engesser-Cesar C, Anderson AJ, Basso DM, Edgerton VR, Cotman CW (2005) Voluntary wheel running improves recovery from a moderate spinal cord injury. J Neurotrauma 22:157–171

    Article  PubMed  Google Scholar 

  • Febinger HY, George A, Priestley J, Toth LA, Opp MR (2014) Effects of housing condition and cage change on characteristics of sleep in mice. J Am Assoc Lab Anim Sci 53:29–37

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fone KC, Porkess MV (2008) Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev 32:1087–1102

    Article  CAS  PubMed  Google Scholar 

  • Friedman EH (1993) Neurobiology of depression in stroke patients. Stroke J Cereb Circ 24:1762

    CAS  Google Scholar 

  • Gardner J, Oswald A (2004) How is mortality affected by money, marriage, and stress? J Health Econ 23:1181–1207

    Article  PubMed  Google Scholar 

  • Gerretsen P, Graff-Guerrero A, Menon M, Pollock BG, Kapur S, Vasdev N, Houle S, Mamo D (2010) Is desire for social relationships mediated by the serotonergic system in the prefrontal cortex? An [(18)F]setoperone PET study. Soc Neurosci 5:375–383

    Article  PubMed  Google Scholar 

  • Glass TA, Dym B, Greenberg S, Rintell D, Roesch C, Berkman LF (2000) Psychosocial intervention in stroke: Families in Recovery from Stroke Trial (FIRST). Am J Orthopsychiatry 70:169–181

    Article  CAS  PubMed  Google Scholar 

  • Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics, C. & Stroke Statistics, S (2013) Executive summary: heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation 127:143–152

    Article  PubMed  Google Scholar 

  • Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics, C. & Stroke Statistics, S (2014) Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation 129:e28–e292

    Article  PubMed  Google Scholar 

  • Gordon CJ, Becker P, Ali JS (1998) Behavioral thermoregulatory responses of single- and group-housed mice. Physiol Behav 65:255–262

    Article  CAS  PubMed  Google Scholar 

  • Hafner S, Emeny RT, Lacruz ME, Baumert J, Herder C, Koenig W, Thorand B, Ladwig KH, Investigators KS (2011) Association between social isolation and inflammatory markers in depressed and non-depressed individuals: results from the MONICA/KORA study. Brain Behav Immun 25:1701–1707

    Article  CAS  PubMed  Google Scholar 

  • Heffner KL, Waring ME, Roberts MB, Eaton CB, Gramling R (2011) Social isolation, C-reactive protein, and coronary heart disease mortality among community-dwelling adults. Soc Sci Med 72:1482–1488

    Article  PubMed Central  PubMed  Google Scholar 

  • Holson RR, Scallet AC, Ali SF, Turner BB (1991) “Isolation stress” revisited: isolation-rearing effects depend on animal care methods. Physiol Behav 49:1107–1118

    Article  CAS  PubMed  Google Scholar 

  • Holt-Lunstad J, Smith TB, Layton JB (2010) Social relationships and mortality risk: a meta-analytic review. PLoS Med 7:e1000316

    Article  PubMed Central  PubMed  Google Scholar 

  • Horie R, Yamori Y, Nara Y, Sawamura M, Mizushima S (1991) Aggravating effects of isolated caging on the development of hypertension and its complications in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Clin Exp Hypertens Part A Theory Pract 13:859–864

    Article  CAS  Google Scholar 

  • House JS, Landis KR, Umberson D (1988) Social relationships and health. Science 241:540–545

    Article  CAS  PubMed  Google Scholar 

  • Hsiao YH, Chen PS, Chen SH, Gean PW (2011) The involvement of Cdk5 activator p35 in social isolation-triggered onset of early Alzheimer’s disease-related cognitive deficit in the transgenic mice. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 36:1848–1858

    Article  CAS  Google Scholar 

  • Hsiao YH, Kuo JR, Chen SH, Gean PW (2012) Amelioration of social isolation-triggered onset of early Alzheimer’s disease-related cognitive deficit by N-acetylcysteine in a transgenic mouse model. Neurobiol Dis 45:1111–1120

    Article  CAS  PubMed  Google Scholar 

  • Ikeda A, Iso H, Kawachi I, Yamagishi K, Inoue M, Tsugane S, Group, J.S (2008) Social support and stroke and coronary heart disease: the JPHC study cohorts II. Stroke J Cereb Circ 39:768–775

    Article  Google Scholar 

  • Jiang Z, Rompala GR, Zhang S, Cowell RM, Nakazawa K (2013) Social isolation exacerbates schizophrenia-like phenotypes via oxidative stress in cortical interneurons. Biol Psychiatry 73:1024–1034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Juraska JM, Kopcik JR (1988) Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res 450:1–8

    Article  CAS  PubMed  Google Scholar 

  • Kannangara TS, Lucero MJ, Gil-Mohapel J, Drapala RJ, Simpson JM, Christie BR, van Praag H (2011) Running reduces stress and enhances cell genesis in aged mice. Neurobiol Aging 32:2279–2286

    Article  CAS  PubMed  Google Scholar 

  • Karelina K, Norman GJ, Zhang N, DeVries AC (2009a) Social contact influences histological and behavioral outcomes following cerebral ischemia. Exp Neurol 220:276–282

    Article  PubMed  Google Scholar 

  • Karelina K, Norman GJ, Zhang N, Morris JS, Peng H, DeVries AC (2009b) Social isolation alters neuroinflammatory response to stroke. Proc Natl Acad Sci U S A 106:5895–5900

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Karelina K, Stuller KA, Jarrett B, Zhang N, Wells J, Norman GJ, DeVries AC (2011) Oxytocin mediates social neuroprotection after cerebral ischemia. Stroke J Cereb Circ 42:3606–3611

    Article  CAS  Google Scholar 

  • Kaufmann JA, Bickford PC, Taglialatela G (2001) Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fisher-344 rats. J Neurochem 76:1099–1108

    Article  CAS  PubMed  Google Scholar 

  • Kim ES, Park N, Peterson C (2013) Perceived neighborhood social cohesion and stroke. Soc Sci Med 97:49–55

    Article  PubMed  Google Scholar 

  • Krause N, Shaw B, Liang J (2011) Social relationships in religious institutions and healthy lifestyles. Health Educ Behav Off Publ Soc Publ Health Educ 38:25–38

    Article  Google Scholar 

  • Kroenke CH, Kubzansky LD, Schernhammer ES, Holmes MD, Kawachi I (2006) Social networks, social support, and survival after breast cancer diagnosis. J Clin Oncol Off J Am Soc Clin Oncol 24:1105–1111

    Article  Google Scholar 

  • Lai MC, Holmes GL, Lee KH, Yang SN, Wang CA, Wu CL, Tiao MM, Hsieh CS, Lee CH, Huang LT (2006) Effect of neonatal isolation on outcome following neonatal seizures in rats–the role of corticosterone. Epilepsy Res 68:123–136

    Article  CAS  PubMed  Google Scholar 

  • Lai MC, Lui CC, Yang SN, Wang JY, Huang LT (2009) Epileptogenesis is increased in rats with neonatal isolation and early-life seizure and ameliorated by MK-801: a long-term MRI and histological study. Pediatr Res 66:441–447

    Article  PubMed  Google Scholar 

  • Lett HS, Blumenthal JA, Babyak MA, Strauman TJ, Robins C, Sherwood A (2005) Social support and coronary heart disease: epidemiologic evidence and implications for treatment. Psychosom Med 67:869–878

    Article  PubMed  Google Scholar 

  • Leutz W, Nonnenkamp L, Dickinson L, Brody K (2005) Utilization and costs of home-based and community-based care within a social HMO: trends over an 18-year period. Int J Integr Care 5:e25

    PubMed Central  PubMed  Google Scholar 

  • Leys D, Deplanque D (2006) Thrombolysis beyond the three-hour time window. Clin Exp Hypertens 28:313–316

    Article  PubMed  Google Scholar 

  • Lieberwirth C, Liu Y, Jia X, Wang Z (2012) Social isolation impairs adult neurogenesis in the limbic system and alters behaviors in female prairie voles. Horm Behav 62:357–366

    Article  PubMed Central  PubMed  Google Scholar 

  • Liu H, Wang Z (2005) Effects of social isolation stress on immune response and survival time of mouse with liver cancer. World J Gastroenterol 11:5902–5904

    PubMed  Google Scholar 

  • Liu J, Dietz K, DeLoyht JM, Pedre X, Kelkar D, Kaur J, Vialou V, Lobo MK, Dietz DM, Nestler EJ, Dupree J, Casaccia P (2012) Impaired adult myelination in the prefrontal cortex of socially isolated mice. Nat Neurosci 15:1621–1623

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu X, Wu R, Tai F, Ma L, Wei B, Yang X, Zhang X, Jia R (2013) Effects of group housing on stress induced emotional and neuroendocrine alterations. Brain Res 1502:71–80

    Article  CAS  PubMed  Google Scholar 

  • Madden KS, Szpunar MJ, Brown EB (2013) Early impact of social isolation and breast tumor progression in mice. Brain Behav Immun 30(Suppl):S135–141

    Article  PubMed Central  PubMed  Google Scholar 

  • Marder SR, Roth B, Sullivan PF, Scolnick EM, Nestler EJ, Geyer MA, Welnberger DR, Karayiorgou M, Guidotti A, Gingrich J, Akbarian S, Buchanan RW, Lieberman JA, Conn PJ, Haggarty SJ, Law AJ, Campbell B, Krystal JH, Moghaddam B, Sawa A, Caron MG, George SR, Allen JA, Solis M (2011) Advancing drug discovery for schizophrenia. Ann N Y Acad Sci 1236:30–43

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marsden CA, King MV, Fone KC (2011) Influence of social isolation in the rat on serotonergic function and memory–relevance to models of schizophrenia and the role of 5-HT(6) receptors. Neuropharmacology 61:400–407

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto K, Nomura H, Murakami Y, Taki K, Takahata H, Watanabe H (2003) Long-term social isolation enhances picrotoxin seizure susceptibility in mice: up-regulatory role of endogenous brain allopregnanolone in GABAergic systems. Pharmacol Biochem Behav 75:831–835

    Article  CAS  PubMed  Google Scholar 

  • Mechakra-Tahiri SD, Zunzunegui MV, Preville M, Dube M (2010) Gender, social relationships and depressive disorders in adults aged 65 and over in Quebec. Chron Dis Can 30:56–65

    Google Scholar 

  • Moller M, Du Preez JL, Emsley R, Harvey BH (2012) Social isolation rearing in rats alters plasma tryptophan metabolism and is reversed by sub-chronic clozapine treatment. Neuropharmacology 62:2499–2506

    Article  CAS  PubMed  Google Scholar 

  • Moller M, Du Preez JL, Viljoen FP, Berk M, Emsley R, Harvey BH (2013) Social isolation rearing induces mitochondrial, immunological, neurochemical and behavioural deficits in rats, and is reversed by clozapine or N-acetyl cysteine. Brain Behav Immun 30:156–167

    Article  CAS  PubMed  Google Scholar 

  • Morris PL, Robinson RG, Andrzejewski P, Samuels J, Price TR (1993) Association of depression with 10-year poststroke mortality. Am J Psychiatry 150:124–129

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa-Toyama Y, Zhang S, Krieger M (2012) Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease. PLoS One 7:e47965

    Article  PubMed Central  PubMed  Google Scholar 

  • Nation DA, Szeto A, Mendez AJ, Brooks LG, Zaias J, Herderick EE, Gonzales J, Noller CM, Schneiderman N, McCabe PM (2010) Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE−/− mice. Psychosom Med 72:376–382

    Article  CAS  PubMed  Google Scholar 

  • Nithianantharajah J, Hannan AJ (2006) Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 7:697–709

    Article  CAS  PubMed  Google Scholar 

  • Nithianantharajah J, Hannan AJ (2009) The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders. Prog Neurobiol 89:369–382

    Article  PubMed  Google Scholar 

  • O’Keefe LM, Doran SJ, Mwilambwe-Tshilobo L, Conti LH, Venna VR, McCullough LD (2014) Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice. Behav Brain Res 260:162–170

    Article  PubMed Central  PubMed  Google Scholar 

  • Olson MM, Trevino DB, Islam J, Denner L (2010) The biopsychosocial milieu of type 2 diabetes: an exploratory study of the impact of social relationships on a chronic inflammatory disease. Int J Psychiatry Med 40:289–305

    Article  PubMed  Google Scholar 

  • Ouimet MA, Primeau F, Cole MG (2001) Psychosocial risk factors in poststroke depression: a systematic review. Can J Psychiatry 46:819–828

    CAS  PubMed  Google Scholar 

  • Petrea RE, Beiser AS, Seshadri S, Kelly-Hayes M, Kase CS, Wolf PA (2009) Gender differences in stroke incidence and poststroke disability in the Framingham heart study. Stroke J Cereb Circ 40:1032–1037

    Article  Google Scholar 

  • Petrea RE, Koyfman F, Pikula A, Romero JR, Viereck J, Babikian VL, Kase CS, Nguyen TN (2013) Acute stroke, catheter related venous thrombosis, and paradoxical cerebral embolism: report of two cases. J Neuroimaging Off J Am Soc Neuroimaging 23:111–114

    Article  Google Scholar 

  • Quan MN, Tian YT, Xu KH, Zhang T, Yang Z (2010) Post weaning social isolation influences spatial cognition, prefrontal cortical synaptic plasticity and hippocampal potassium ion channels in Wistar rats. Neuroscience 169:214–222

    Article  CAS  PubMed  Google Scholar 

  • Ros-Simo C, Valverde O (2012) Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function. Pharmacol Biochem Behav 102:434–441

    Article  CAS  PubMed  Google Scholar 

  • Roy-O’Reilly M, McCullough LD (2014) Sex differences in stroke: the contribution of coagulation. Exp Neurol. doi:10.1016/j.expneurol.2014.02.011

  • Schiavone S, Sorce S, Dubois-Dauphin M, Jaquet V, Colaianna M, Zotti M, Cuomo V, Trabace L, Krause KH (2009) Involvement of NOX2 in the development of behavioral and pathologic alterations in isolated rats. Biol Psychiatry 66:384–392

    Article  CAS  PubMed  Google Scholar 

  • Schrijver NC, Bahr NI, Weiss IC, Wurbel H (2002) Dissociable effects of isolation rearing and environmental enrichment on exploration, spatial learning and HPA activity in adult rats. Pharmacol Biochem Behav 73:209–224

    Article  CAS  PubMed  Google Scholar 

  • Shankar A, McMunn A, Banks J, Steptoe A (2011) Loneliness, social isolation, and behavioral and biological health indicators in older adults. Health Psychol Off J Div Health Psychol Am Psychol Assoc 30:377–385

    Google Scholar 

  • Stewart M, Barnfather A, Neufeld A, Warren S, Letourneau N, Liu L (2006) Accessible support for family caregivers of seniors with chronic conditions: from isolation to inclusion. Can J Aging La Rev Can Vieil 25:179–192

    Article  Google Scholar 

  • Stranahan AM, Khalil D, Gould E (2006) Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci 9:526–533

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stuller KA, Jarrett B, DeVries AC (2012) Stress and social isolation increase vulnerability to stroke. Exp Neurol 233:33–39

    Article  PubMed  Google Scholar 

  • Takatsu-Coleman AL, Patti CL, Zanin KA, Zager A, Carvalho RC, Borcoi AR, Ceccon LM, Berro LF, Tufik S, Andersen ML, Frussa-Filho R (2013) Short-term social isolation induces depressive-like behaviour and reinstates the retrieval of an aversive task: mood-congruent memory in male mice? J Psychiatry Neurosci 38:259–268

    Article  PubMed Central  PubMed  Google Scholar 

  • Trigg R, Wood VA, Hewer RL (1999) Social reintegration after stroke: the first stages in the development of the Subjective Index of Physical and Social Outcome (SIPSO). Clin Rehabil 13:341–353

    Article  CAS  PubMed  Google Scholar 

  • Umberson D, Montez JK (2010) Social relationships and health: a flashpoint for health policy. J Health Soc Behav 51(Suppl):S54–66

    Article  PubMed Central  PubMed  Google Scholar 

  • Venna VR, McCullough LD (2011) “Won’t you be my neighbor?”: deciphering the mechanisms of neuroprotection induced by social interaction. Stroke J Cereb Circ 42:3329–3330

    Article  Google Scholar 

  • Venna VR, Weston G, Benashski SE, Tarabishy S, Liu F, Li J, Conti LH, McCullough LD (2012) NF-kappaB contributes to the detrimental effects of social isolation after experimental stroke. Acta Neuropathol 124:425–438

    Article  PubMed Central  PubMed  Google Scholar 

  • Venna VR, Xu Y, Doran SJ, Patrizz A, McCullough LD (2014) Social interaction plays a critical role in neurogenesis and recovery after stroke. Transl Psychiatry 4:e351

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Verma R, Friedler B, Harris N, Venna VR, McCullough LD (2014) Impact of Post Stroke Isolation on Sociability and Depressive Behavior. Stroke 45:AWP88

    Google Scholar 

  • Vogt TM, Mullooly JP, Ernst D, Pope CR, Hollis JF (1992) Social networks as predictors of ischemic heart disease, cancer, stroke and hypertension: incidence, survival and mortality. J Clin Epidemiol 45:659–666

    Article  CAS  PubMed  Google Scholar 

  • Wallace DL, Han MH, Graham DL, Green TA, Vialou V, Iniguez SD, Cao JL, Kirk A, Chakravarty S, Kumar A, Krishnan V, Neve RL, Cooper DC, Bolanos CA, Barrot M, McClung CA, Nestler EJ (2009) CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nat Neurosci 12:200–209

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang SH, Zhang ZJ, Guo YJ, Zhou H, Teng GJ, Chen BA (2009) Anhedonia and activity deficits in rats: impact of post-stroke depression. J Psychopharmacol 23:295–304

    Article  CAS  PubMed  Google Scholar 

  • Whyte EM, Mulsant BH (2002) Post stroke depression: epidemiology, pathophysiology, and biological treatment. Biol Psychiatry 52:253–264

    Article  PubMed  Google Scholar 

  • Yevchak AM, Loeb SJ, Fick DM (2008) Promoting cognitive health and vitality: a review of clinical implications. Geriatr Nurs 29:302–310

    Article  PubMed  Google Scholar 

  • Zhu SW, Pham TM, Aberg E, Brene S, Winblad B, Mohammed AH, Baumans V (2006) Neurotrophin levels and behaviour in BALB/c mice: impact of intermittent exposure to individual housing and wheel running. Behav Brain Res 167:1–8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Institutes of Health grants R01 NSO77769 and NS055215 (to L.D.M.) and American Heart Association grant 11POST7430045 to V.R.V

Author information

Affiliations

  1. Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Venugopal Reddy Venna & Louise D. McCullough

  2. Department of Neurology, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Louise D. McCullough

  3. The Stroke Center at Hartford Hospital, 85 Jefferson Street, Hartford, CT, 06102, USA

    Louise D. McCullough

Authors
  1. Venugopal Reddy Venna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Louise D. McCullough
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Louise D. McCullough.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Venna, V.R., McCullough, L.D. Role of social factors on cell death, cerebral plasticity and recovery after stroke. Metab Brain Dis 30, 497–506 (2015). https://doi.org/10.1007/s11011-014-9544-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9544-1

Keywords

  • Social isolation
  • Social interaction
  • Brain plasticity
  • Stroke
  • Behavior