Metabolic Brain Disease

, Volume 30, Issue 2, pp 497–506 | Cite as

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

  • Venugopal Reddy Venna
  • Louise D. McCullough
Research Article


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.


Social isolation Social interaction Brain plasticity Stroke Behavior 



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


  1. 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 34:122–126CrossRefGoogle Scholar
  2. 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 97:385–393CrossRefPubMedGoogle Scholar
  3. 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 37:1368–1373CrossRefGoogle Scholar
  4. 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 28:540–558CrossRefPubMedGoogle Scholar
  5. 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 289:3106–3116CrossRefPubMedGoogle Scholar
  6. 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 311:864–868CrossRefPubMedGoogle Scholar
  7. Boden-Albala B, Litwak E, Elkind MS, Rundek T, Sacco RL (2005) Social isolation and outcomes post stroke. Neurology 64:1888–1892CrossRefPubMedGoogle Scholar
  8. 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 30:148–156CrossRefPubMedGoogle Scholar
  9. Bondar NP, Kudriavtseva NN (2005) Impaired social recognition in male mice with repeated experience of aggression. Zh Vyssh Nerv Deiat Im I P Pavlova 55:378–384PubMedGoogle Scholar
  10. Burton CR (2000) Living with stroke: a phenomenological study. J Adv Nurs 32:301–309CrossRefPubMedGoogle Scholar
  11. 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
  12. Cacioppo JT, Hawkley LC (2009) Perceived social isolation and cognition. Trends Cogn Sci 13:447–454CrossRefPubMedCentralPubMedGoogle Scholar
  13. 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 97:977–991CrossRefPubMedCentralPubMedGoogle Scholar
  14. Cacioppo JT, Hawkley LC, Norman GJ, Berntson GG (2011) Social isolation. Ann N Y Acad Sci 1231:17–22CrossRefPubMedCentralPubMedGoogle Scholar
  15. Cheng E, Vickrey B (2006) Is there a relationship between prestroke social isolation and outcomes following stroke? Nature clinical practice. Neurology 2:16–17PubMedGoogle Scholar
  16. Christakis NA, Fowler JH (2007) The spread of obesity in a large social network over 32 years. N Engl J Med 357:370–379CrossRefPubMedGoogle Scholar
  17. Christakis NA, Fowler JH (2013) Social contagion theory: examining dynamic social networks and human behavior. Stat Med 32:556–577CrossRefPubMedGoogle Scholar
  18. 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 42:1212–1217CrossRefGoogle Scholar
  19. 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 36:2006–2011CrossRefGoogle Scholar
  20. 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 98:11824–11828CrossRefPubMedCentralPubMedGoogle Scholar
  21. 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 32:587–603CrossRefPubMedGoogle Scholar
  22. Drage MG, Heinrichs SC (2005) Phenotyping the untouchables: environmental enhancement of behavioral and physiological activation in seizure-prone El mice. Epilepsy Behav 6:35–42CrossRefPubMedGoogle Scholar
  23. 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 22:157–171CrossRefPubMedGoogle Scholar
  24. 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 53:29–37PubMedCentralPubMedGoogle Scholar
  25. Fone KC, Porkess MV (2008) Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev 32:1087–1102CrossRefPubMedGoogle Scholar
  26. Friedman EH (1993) Neurobiology of depression in stroke patients. Stroke J Cereb Circ 24:1762Google Scholar
  27. Gardner J, Oswald A (2004) How is mortality affected by money, marriage, and stress? J Health Econ 23:1181–1207CrossRefPubMedGoogle Scholar
  28. 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 5:375–383CrossRefPubMedGoogle Scholar
  29. 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 70:169–181CrossRefPubMedGoogle Scholar
  30. 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 127:143–152CrossRefPubMedGoogle Scholar
  31. 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–e292CrossRefPubMedGoogle Scholar
  32. Gordon CJ, Becker P, Ali JS (1998) Behavioral thermoregulatory responses of single- and group-housed mice. Physiol Behav 65:255–262CrossRefPubMedGoogle Scholar
  33. 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 25:1701–1707CrossRefPubMedGoogle Scholar
  34. 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 72:1482–1488CrossRefPubMedCentralPubMedGoogle Scholar
  35. Holson RR, Scallet AC, Ali SF, Turner BB (1991) “Isolation stress” revisited: isolation-rearing effects depend on animal care methods. Physiol Behav 49:1107–1118CrossRefPubMedGoogle Scholar
  36. Holt-Lunstad J, Smith TB, Layton JB (2010) Social relationships and mortality risk: a meta-analytic review. PLoS Med 7:e1000316CrossRefPubMedCentralPubMedGoogle Scholar
  37. 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 13:859–864CrossRefGoogle Scholar
  38. House JS, Landis KR, Umberson D (1988) Social relationships and health. Science 241:540–545CrossRefPubMedGoogle Scholar
  39. 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 36:1848–1858CrossRefGoogle Scholar
  40. 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 45:1111–1120CrossRefPubMedGoogle Scholar
  41. 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 39:768–775CrossRefGoogle Scholar
  42. 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 73:1024–1034CrossRefPubMedCentralPubMedGoogle Scholar
  43. Juraska JM, Kopcik JR (1988) Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res 450:1–8CrossRefPubMedGoogle Scholar
  44. 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 32:2279–2286CrossRefPubMedGoogle Scholar
  45. Karelina K, Norman GJ, Zhang N, DeVries AC (2009a) Social contact influences histological and behavioral outcomes following cerebral ischemia. Exp Neurol 220:276–282CrossRefPubMedGoogle Scholar
  46. 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 106:5895–5900CrossRefPubMedCentralPubMedGoogle Scholar
  47. 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 42:3606–3611CrossRefGoogle Scholar
  48. 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 76:1099–1108CrossRefPubMedGoogle Scholar
  49. Kim ES, Park N, Peterson C (2013) Perceived neighborhood social cohesion and stroke. Soc Sci Med 97:49–55CrossRefPubMedGoogle Scholar
  50. Krause N, Shaw B, Liang J (2011) Social relationships in religious institutions and healthy lifestyles. Health Educ Behav Off Publ Soc Publ Health Educ 38:25–38CrossRefGoogle Scholar
  51. 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 24:1105–1111CrossRefGoogle Scholar
  52. 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 68:123–136CrossRefPubMedGoogle Scholar
  53. 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 66:441–447CrossRefPubMedGoogle Scholar
  54. 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 67:869–878CrossRefPubMedGoogle Scholar
  55. 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:e25PubMedCentralPubMedGoogle Scholar
  56. Leys D, Deplanque D (2006) Thrombolysis beyond the three-hour time window. Clin Exp Hypertens 28:313–316CrossRefPubMedGoogle Scholar
  57. 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 62:357–366CrossRefPubMedCentralPubMedGoogle Scholar
  58. Liu H, Wang Z (2005) Effects of social isolation stress on immune response and survival time of mouse with liver cancer. World J Gastroenterol 11:5902–5904PubMedGoogle Scholar
  59. 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 15:1621–1623CrossRefPubMedCentralPubMedGoogle Scholar
  60. 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 1502:71–80CrossRefPubMedGoogle Scholar
  61. Madden KS, Szpunar MJ, Brown EB (2013) Early impact of social isolation and breast tumor progression in mice. Brain Behav Immun 30(Suppl):S135–141CrossRefPubMedCentralPubMedGoogle Scholar
  62. 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 1236:30–43CrossRefPubMedCentralPubMedGoogle Scholar
  63. 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 61:400–407CrossRefPubMedGoogle Scholar
  64. 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 75:831–835CrossRefPubMedGoogle Scholar
  65. 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 30:56–65Google Scholar
  66. 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 62:2499–2506CrossRefPubMedGoogle Scholar
  67. 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 30:156–167CrossRefPubMedGoogle Scholar
  68. Morris PL, Robinson RG, Andrzejewski P, Samuels J, Price TR (1993) Association of depression with 10-year poststroke mortality. Am J Psychiatry 150:124–129CrossRefPubMedGoogle Scholar
  69. 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:e47965CrossRefPubMedCentralPubMedGoogle Scholar
  70. 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 72:376–382CrossRefPubMedGoogle Scholar
  71. Nithianantharajah J, Hannan AJ (2006) Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 7:697–709CrossRefPubMedGoogle Scholar
  72. Nithianantharajah J, Hannan AJ (2009) The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders. Prog Neurobiol 89:369–382CrossRefPubMedGoogle Scholar
  73. 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 260:162–170CrossRefPubMedCentralPubMedGoogle Scholar
  74. 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 40:289–305CrossRefPubMedGoogle Scholar
  75. Ouimet MA, Primeau F, Cole MG (2001) Psychosocial risk factors in poststroke depression: a systematic review. Can J Psychiatry 46:819–828PubMedGoogle Scholar
  76. 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 40:1032–1037CrossRefGoogle Scholar
  77. 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 23:111–114CrossRefGoogle Scholar
  78. 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 169:214–222CrossRefPubMedGoogle Scholar
  79. Ros-Simo C, Valverde O (2012) Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function. Pharmacol Biochem Behav 102:434–441CrossRefPubMedGoogle Scholar
  80. 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
  81. 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 66:384–392CrossRefPubMedGoogle Scholar
  82. 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 73:209–224CrossRefPubMedGoogle Scholar
  83. 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 30:377–385Google Scholar
  84. 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 25:179–192CrossRefGoogle Scholar
  85. Stranahan AM, Khalil D, Gould E (2006) Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci 9:526–533CrossRefPubMedCentralPubMedGoogle Scholar
  86. Stuller KA, Jarrett B, DeVries AC (2012) Stress and social isolation increase vulnerability to stroke. Exp Neurol 233:33–39CrossRefPubMedGoogle Scholar
  87. 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 38:259–268CrossRefPubMedCentralPubMedGoogle Scholar
  88. 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 13:341–353CrossRefPubMedGoogle Scholar
  89. Umberson D, Montez JK (2010) Social relationships and health: a flashpoint for health policy. J Health Soc Behav 51(Suppl):S54–66CrossRefPubMedCentralPubMedGoogle Scholar
  90. Venna VR, McCullough LD (2011) “Won’t you be my neighbor?”: deciphering the mechanisms of neuroprotection induced by social interaction. Stroke J Cereb Circ 42:3329–3330CrossRefGoogle Scholar
  91. 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 124:425–438CrossRefPubMedCentralPubMedGoogle Scholar
  92. 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:e351CrossRefPubMedCentralPubMedGoogle Scholar
  93. Verma R, Friedler B, Harris N, Venna VR, McCullough LD (2014) Impact of Post Stroke Isolation on Sociability and Depressive Behavior. Stroke 45:AWP88Google Scholar
  94. 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 45:659–666CrossRefPubMedGoogle Scholar
  95. 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 12:200–209CrossRefPubMedCentralPubMedGoogle Scholar
  96. 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 23:295–304CrossRefPubMedGoogle Scholar
  97. Whyte EM, Mulsant BH (2002) Post stroke depression: epidemiology, pathophysiology, and biological treatment. Biol Psychiatry 52:253–264CrossRefPubMedGoogle Scholar
  98. Yevchak AM, Loeb SJ, Fick DM (2008) Promoting cognitive health and vitality: a review of clinical implications. Geriatr Nurs 29:302–310CrossRefPubMedGoogle Scholar
  99. 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 167:1–8CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Venugopal Reddy Venna
    • 1
  • Louise D. McCullough
    • 1
    • 2
    • 3
  1. 1.Department of NeuroscienceUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Department of NeurologyFarmingtonUSA
  3. 3.The Stroke Center at Hartford HospitalHartfordUSA

Personalised recommendations