Aging, inflammation and depressive behavior: a review
DOI:
https://doi.org/10.7175/rhc.v6i2.1170Keywords:
Metabolic syndrome, Inflammation, AgingAbstract
One of the most common co-morbidities of cerebrovascular disorders is neuroinflammation, a hallmark and decisive contributor to many central nervous system (CNS) diseases. Although neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment or after cerebral insult such as stroke. Moreover, a number of highly prevalent risk factors such as hypertension, diabetes and atherosclerosis are increasingly understood to act as “silent contributors” to neuroinflammation – not only establishing the condition as a central pathophysiological mechanism, but also constantly fuelling it. Mild, but continuous neuroinflammation can provide the ground for disorders such as cerebral small vessel disease (cSVD) and subsequent dementia. Acute neuroinflammation, often in the context of traumatic or ischemic CNS lesions, aggravates the acute damage and can lead to depression, post-stroke dementia and neurodegeneration. All of these sequelae impair recovery and provide the ground for further cerebrovascular events.
References
Olesen J, Gustavsson A, Svensson M, et al.; CDBE2010 study group. The economic cost of brain disorders in Europe. Eur J Neurol 2012; 19: 155-62; http://dx.doi.org/10.1111/j.1468-1331.2011.03590.x
Sivenius J, Torppa J, Tuomilehto J, et al. Modelling the burden of stroke in Finland until 2030. Int J Stroke 2009; 4: 340-5; http://dx.doi.org/10.1111/j.1747-4949.2009.00330.x
Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke 1988; 19: 1497-500; http://dx.doi.org/10.1161/01.STR.19.12.1497
Burn J, Dennis M, Bamford J, et al. Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke 1994; 25: 333-7; http://dx.doi.org/10.1161/01.STR.25.2.333
Appelros P, Nydevik I, Viitanen M. Poor Outcome After First-Ever Stroke. Predictors for Death, Dependency, and Recurrent Stroke Within the First Year. Stroke 2002; 34: 122-6; http://dx.doi.org/10.1161/01.STR.0000047852.05842.3C
Donnan GA, Davis SM. Breaking the 3 h barrier for treatment of acute ischaemic stroke. Lancet Neurol 2008; 7: 981-2; http://dx.doi.org/10.1016/S1474-4422(08)70230-8
Murray C, Sanderson DJ, Barkus C, et al. Systemic inflammation induces acute working memory deficits in the primed brain: Relevance for delirium. Neurobiol Aging 2010; 33: 603-6; http://dx.doi.org/10.1016/j.neurobiolaging.2010.04.002
Buga AM, Di Napoli M, Popa-Wagner A. Preclinical models of stroke in aged animals with or without comorbidities: role of neuroinflammation. Biogerontology 2013, 14: 651-62; http://dx.doi.org/10.1007/s10522-013-9465-0
Popa-Wagner A, Buga AM, Tica AA, et al. Perfusion deficits, inflammation and aging precipitate depressive behaviour. Biogerontology 2014, 15: 439-48; http://dx.doi.org/10.1007/s10522-014-9516-1
Allison DJ, Ditor DS. The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. J Neuroinflammation 2014, 11: 151; http://dx.doi.org/10.1186/s12974-014-0151-1
Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010; 72: 219-46; http://dx.doi.org/10.1146/annurev-physiol-021909-135846
Poulsen P, Ohm Kyvik K, Vaag A, et al. Heritability of Type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance ± a population-based twin study. Diabetologia 1999; 42: 139-45; http://dx.doi.org/10.1007/s001250051131
Cornelis MC, Hu FB. Gene-environment interactions in the development of type 2 diabetes: recent progress and continuing challenges. Annu Rev Nutr 2012; 32:245-259; http://dx.doi.org/10.1146/annurev-nutr-071811-150648
Kim JG, Mandal PK, Choi KD, et al. Beneficial dietary effect of turmeric and sulphur on weight gain, fat deposition and lipid profile of serum and liver in rats. J Food Sci Technol 2014; 51:774-9; http://dx.doi.org/10.1007/s13197-011-0569-8
Olsen TS, Dehlendorff C, Petersen HG, et al. Body mass index and poststroke mortality. Neuroepidemiology 2008; 30: 93-100; http://dx.doi.org/10.1159/000118945
Towfighi A, Ovbiagele B. The impact of body mass index on mortality after stroke. Stroke 2009; 40: 2704-8; http://dx.doi.org/10.1161/STROKEAHA.109.550228
Vemmos K, Ntaios G, Spengos K, et al. Association between obesity and mortality after acute first-ever stroke: the obesity-stroke paradox. Stroke 2011; 42: 30-6; http://dx.doi.org/10.1161/STROKEAHA.110.593434
Ovbiagele B, Bath PM, Cotton D, et al. Obesity and recurrent vascular risk after a recent ischemic stroke. Stroke 2011; 42: 3397-402; http://dx.doi.org/10.1161/STROKEAHA.111.624957
Andersen KK, Olsen TS. The obesity paradox in stroke: lower mortality and lower risk of readmission for recurrent stroke in obese stroke patients. Int J Stroke 2015; 10: 99-104; http://dx.doi.org/10.1111/ijs.12016
Ryu WS, Lee SH, Kim CK, et al. Body mass index, initial neurological severity and long-term mortality in ischemic stroke. Cerebrovasc Dis 2011; 32: 170-6; http://dx.doi.org/10.1159/000328250
Zhao L, Du W, Zhao X, et al. Favorable functional recovery in overweight ischemic stroke survivors: findings from the China National Stroke Registry. J Stroke Cerebrovasc Dis 2014; 23: e201-6; http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.002
Burke DT, Al-Adawi S. Effect of Body Mass Index on Stroke Rehabilitation. J Stroke Cerebrovasc Dis. 2014; 23: e201-6; http://dx.doi.org/10.1016/j.apmr.2014.01.019
Chiquete E, Cantú-Brito C. Obesity paradox and functional recovery in first-ever acute ischemic stroke survivors: The PREMIER study. Rev Neurol 2010; 51: 705-13
Kalichman L, Rodrigues B, Gurvich D, et al. Impact of patient’s weight on stroke rehabilitation results. Am J Phys Med Rehabil 2007; 86: 650-5; http://dx.doi.org/10.1097/PHM.0b013e318115f41b
Razinia T, Saver JL, Liebeskind DS, et al. Body mass index and hospital discharge outcomes after ischemic stroke. Arch Neurol 2007; 64: 388-91; http://dx.doi.org/10.1001/archneur.64.3.388
Tanizaki Y, Kiyohara Y, Kato I, et al. Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study. Stroke 2000; 31: 2616-22; http://dx.doi.org/10.1161/01.STR.31.11.2616
Kessler D, Sharp D, Lewis G. Screening for depression in primary care. Br J Gen Pract 2005; 55: 659-60
Knol MJ, Twisk JW, Beekman AT, et al. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 2006; 49: 837-84; http://dx.doi.org/10.1007/s00125-006-0159-x
Evans J, Heron J, Lewis G, et al.; ALSPAC study team. Negative self-schemas and the onset of depression in women: longitudinal study. Negative self-schemas and the onset of depression in women: longitudinal study. Br J Psychiatry 2005; 186: 302-7; http://dx.doi.org/10.1192/bjp.186.4.302
Gildengers AG, Whyte EM, Drayer RA, et al. Medical burden in late-life bipolar and major depressive disorders. Am J Geriatr Psychiatry 2008; 16: 194-200; http://dx.doi.org/10.1097/JGP.0b013e318157c5b1
Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature 2008; 455: 894-902; http://dx.doi.org/10.1038/nature07455
Trivedi MH, Fava M, Marangell LB, et al. Use of treatment algorithms for depression. Prim Care Companion. J Clin Psychiatry 2006; 8: 291-8; http://dx.doi.org/10.4088/PCC.v08n0506
Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006; 354: 1231-42; http://dx.doi.org/10.1056/NEJMoa052963
Najjar S, Pearlman DM, Devinsky O, et al. Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence. J Neuroinflammation 2013; 10: 142; http://dx.doi.org/10.1186/1742-2094-10-142
Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009; 65: 732-41; http://dx.doi.org/10.1016/j.biopsych.2008.11.029
Lanquillon S, Krieg JC, Bening-Abu-Shach U, et al. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 2000; 22: 370-9; http://dx.doi.org/10.1016/S0893-133X(99)00134-7
Papakostas GI, Fan H, Tedeschini E. Severe and anxious depression: combining definitions of clinical sub-types to identify patients differentially responsive to selective serotonin reuptake inhibitors. Eur Neuropsychopharmacol 2012; 22: 347-55; http://dx.doi.org/10.1016/j.euroneuro.2011.09.009
Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry 2012; 83: 495-502; http://dx.doi.org/10.1136/jnnp-2011-301779
Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013; 70: 31-41; http://dx.doi.org/10.1001/2013.jamapsychiatry.4
Sluzewska A, Sobieska M, Rybakowski JK. Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression. Neuropsychobiology 1997; 35: 123-7; http://dx.doi.org/10.1159/000119332
Nemeroff CB, Heim CM, Thase ME, et al. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of majordepression and childhood trauma. Proc Natl Acad Sci U S A 2003; 100:14293-6; http://dx.doi.org/10.1073/pnas.2336126100
Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci U S A 2007; 104: 1319-24; http://dx.doi.org/10.1073/pnas.0610362104
Danese A, Moffitt TE, Pariante CM, et al. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 2008; 65: 409-15; http://dx.doi.org/10.1001/archpsyc.65.4.409
Baune BT, Smith E, Reppermund S, et al. Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging: the prospective Sydney Memory and Aging Study. Psychoneuroendocrinology 2012; 37: 1521-30; http://dx.doi.org/10.1016/j.psyneuen.2012.02.006
Caraci F, Copani A, Nicoletti F, et al. Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets. Eur J Pharmacol 2010; 626: 64–71; http://dx.doi.org/10.1016/j.ejphar.2009.10.022
Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009; 24: 27-53; http://dx.doi.org/10.1007/s11011-008-9118-1
Capuron, L, Miller, A.H. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol. Ther 2011; 130: 226-38; http://dx.doi.org/10.1016/j.pharmthera.2011.01.014
Penninx BW, Kritchevsky SB, Yaffe K, et al. Inflammatory markers and depressed mood in older persons: results from the health, aging and body composition study. Biol Psychiatry 2003; 54: 566-72; http://dx.doi.org/10.1016/S0006-3223(02)01811-5
Tiemeier H, Hofman A, van Tuijl HR, et al. Inflammatory proteins and depression in the elderly. Epidemiology 2003; 14: 103-7; http://dx.doi.org/10.1097/00001648-200301000-00025
Bremmer MA, Beekman AT, Deeg DJ, et al. Inflammatory markers in late-life depression: results from a population-based study. J Affect. Disord 2008; 106: 249-55; http://dx.doi.org/10.1016/j.jad.2007.07.002
van den Biggelaar AH, Gussekloo J, de Craen AJ, et al. Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. Exp Gerontol 2007; 42: 693-701; http://dx.doi.org/10.1016/j.exger.2007.01.011
Milaneschi Y, Corsi AM, Penninx BW, et al. Interleukin-1 receptor antagonist and incident depressive symptoms over 6 years in older persons: the InCHIANTI study. Biol Psychiatry 2009; 65: 973-8; http://dx.doi.org/10.1016/j.biopsych.2008.11.011
Stewart JW, McGrath PJ, Quitkin FM, et al. DSM-IV depression with atypical features: is it valid? Neuropsychopharmacology 2009; 34: 2625-32; http://dx.doi.org/10.1038/npp.2009.99
Dantzer R, O’Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008; 9: 46-56; http://dx.doi.org/10.1038/nrn2297
Anisman H, Merali Z, Hayley S. Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Prog Neurobiol 2008; 85: 1-74; http://dx.doi.org/10.1016/j.pneurobio.2008.01.004
Dentino AN, Pieper CF, Rao MK, et al. Association of interleukin-6 and other biologic variables with depression in older people living in the community. J Am Geriatr Soc 1999; 47: 6-11
Musselman DL, Miller AH, Porter MR, et al. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 2001; 158: 1252-7; http://dx.doi.org/10.1176/appi.ajp.158.8.1252
Raison CL, Demetrashvili M, Capuron L, et al. Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs 2005; 19: 105-23; http://dx.doi.org/10.2165/00023210-200519020-00002
Capuron L, Miller AH. Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry 2004; 56: 819-24; http://dx.doi.org/10.1016/j.biopsych.2004.02.009
Ghiadoni L, Virdis A, Magagna A, et al. Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 2000; 35: 501-6; http://dx.doi.org/10.1161/01.HYP.35.1.501
Nagata Y, Takahashi A, Ohnishi K, et al. Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. Int J Oncol 2010; 37: 1001-10; http://dx.doi.org/10.3892/ijo_00000751
Tyring S, Gottlieb A, Papp K, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006; 367: 29-35; http://dx.doi.org/10.1016/S0140-6736(05)67763-X
Kekow J, Moots RJ, Emery P, et al. Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: the COMET trial. Ann Rheum Dis 2010; 69: 222-5; http://dx.doi.org/10.1136/ard.2008.102509
Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001; 11: 240-9; http://dx.doi.org/10.1016/S0959-4388(00)00203-8
Sheline YI. Neuroimaging studies of mood disorder effects on the brain. Biol Psychiatry 2003;54: 338-52; http://dx.doi.org/10.1016/S0006-3223(03)00347-0
Harrison RV, Harel N, Panesar J, et al. Blood capillary distribution correlates with hemodynamic-based functional imaging in cerebral cortex. Cereb Cortex 2002; 12: 225-33; http://dx.doi.org/10.1093/cercor/12.3.225
Davalos D, Grutzendler J, Yang G, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005; 8: 752-8; http://dx.doi.org/10.1038/nn1472
Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005; 308: 1314-18; http://dx.doi.org/10.1126/science.1110647
Paolicelli RC, Bolasco G, Pagani F, et al. Synaptic pruning by microglia is necessary for normal brain development. Science 2011; 333: 1456-8; http://dx.doi.org/10.1126/science.1202529
Tremblay MÈ, Lowery RL, Majewska AK. Microglial interactions with synapses are modulated by visual experience. PLoS Biol 2010; 8: e1000527; http://dx.doi.org/10.1371/journal.pbio.1000527
Wake H, Moorhouse AJ, Jinno S, et al. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 2009; 29: 3974-80; http://dx.doi.org/10.1523/JNEUROSCI.4363-08.2009
Schafer DP, Lehrman EK, Kautzman AG, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 2012; 74: 691-705; http://dx.doi.org/10.1016/j.neuron.2012.03.026
Depp CA, Harmell A, Vahia IV. Successful cognitive aging. Curr Top Behav Neurosci 2012; 10: 35-50; http://dx.doi.org/10.1007/7854_2011_158
Gump BB, Matthews KA, Eberly LE, et al.; MRFIT Research Group. Depressive symptoms and mortality in men: results from the Multiple Risk Factor Intervention Trial. Stroke 2005; 36: 98-102; http://dx.doi.org/10.1161/01.STR.0000149626.50127.d0
McIntyre RS, Soczynska JK, Konarski JZ, et al. Should Depressive Syndromes Be Reclassified as “Metabolic Syndrome Type II”? Ann Clin Psychiatry 2007; 19: 257-64; http://dx.doi.org/10.1080/10401230701653377
Bauer ME. Chronic stress and immunosenescence: a review. Neuroimmunomodulation 2008; 15: 241-50; http://dx.doi.org/10.1159/000156467
Wolkowitz OM, Epel ES, Reus VI, et al. Depression gets old fast: do stress and depression accelerate cell aging? Depress Anxiety 2010; 27: 327-38; http://dx.doi.org/10.1002/da.20686
Warsch JR, Rundek T, Paik MC, et al. Association between northern Manhattan study global vascular risk score and successful aging. J Am Geriatr Soc 2013; 61: 519-24; http://dx.doi.org/10.1111/jgs.12166
Berkman LF, Seeman TE, Albert M, et al. High, usual and impaired functioning in community-dwelling older men and women: findings from the MacArthur foundation research network on successful aging. J Clin Epidemiol 1993; 46: 1129-40; http://dx.doi.org/10.1016/0895-4356(93)90112-E
Jeste DV, Savla GN, Thompson WK, et al. Association between older age and more successful aging: critical role of resilience and depression. Am J Psychiatry 2013; 170: 188-96; http://dx.doi.org/10.1176/appi.ajp.2012.12030386
Kessler RC, Birnbaum HG, Shahly V, et al. Age differences in the prevalence and co-morbidity of DSM-IV major depressive episodes: results from the WHO World Mental Health Survey Initiative. Depress Anxiety 2010; 27: 351-64; http://dx.doi.org/10.1002/da.20634
Luppa M, Konig HH, Heider D, et al. Direct costs associated with depressive symptoms in late life: a 4.5-year prospective study. Int Psychogeriatr 2013; 25: 292-302; http://dx.doi.org/10.1017/S1041610212001688
Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: 3095-105; http://dx.doi.org/10.1001/jama.289.23.3095
Brevik EJ, Eikeland RA, Lundervold AJ. Subthreshold depressive symptoms have a negative impact on cognitive functioning in middle-aged and older males. Front Psychol 2013; 4: 309; http://dx.doi.org/10.3389/fpsyg.2013.00309
Grav S, Stordal E, Romild UK, et al. The relationship among neuroticism, extraversion, and depression in the HUNT Study: in relation to age and gender. Issues Ment Heal Nurs 2012; 33: 777-85; http://dx.doi.org/10.3109/01612840.2012.713082
Dombrovski AY, Lenze EJ, Dew MA, et al. Maintenance treatment for old-age depression preserves health-related quality of life: a randomized, controlled trial of paroxetine and interpersonal psychotherapy. J Am Geriatr Soc 2007; 55: 1325-32; http://dx.doi.org/10.1111/j.1532-5415.2007.01292.x
Lenze EJ, Schulz R, Martire LM, et al. The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the cardiovascular health study. J Am Geriatr Soc 2005; 53: 569-75; http://dx.doi.org/10.1111/j.1532-5415.2005.53202.x
Bruunsgaard H, Pedersen M, Pedersen BK. Aging and proinflammatory cytokines. Curr Opin Hematol 2001; 8: 131-6; http://dx.doi.org/10.1097/00062752-200105000-00001
Fagiolo U, Cossarizza A, Santacaterina S, et al. Increased cytokine production by peripheral blood mononuclear cells from healthy elderly people. Ann N Y Acad Sci 1992; 663: 490-3; http://dx.doi.org/10.1111/j.1749-6632.1992.tb38712.x
Fagiolo U, Cossarizza A, Scala E, et al. Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 1993; 23: 2375-8; http://dx.doi.org/10.1002/eji.1830230950
Floyd RA, Hensley K, Jaffery F, et al. Increased oxidative stress brought on by pro-inflammatory cytokines in neurodegenerative processes and the protective role of nitrone-based free radical traps. Life Sci 1999; 65: 1893-9; http://dx.doi.org/10.1016/S0024-3205(99)00443-9
Ye SM, Johnson RW. Increased interleukin-6 expression by microglia from brain of aged mice. J Neuroimmunol 1999; 93: 139-48; http://dx.doi.org/10.1016/S0165-5728(98)00217-3
Akiyama H, Arai T, Kondo H, et al. Cell mediators of inflammation in the Alzheimer disease brain Alzheimer. Dis Assoc Disord 2000; 14: S47-53; http://dx.doi.org/10.1097/00002093-200000001-00008
Capuron L, Su S, Miller AH, et al. Depressive symptoms and metabolic syndrome: is inflammation the underlying link? Biol Psychiatry 2008; 64: 896-900; http://dx.doi.org/10.1016/j.biopsych.2008.05.019
Capuron L, Poitou C, Machaux-Tholliez D, et al. Relationship between adiposity, emotional status and eating behavior in obese women: role of inflammation. Psychol Med 2011; 41: 1517-28; http://dx.doi.org/10.1017/S0033291710001984
Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277-86; http://dx.doi.org/10.2337/diabetes.54.8.2277
Emery CF, Fondow MD, Schneider CM, et al. Gastric bypass surgery is associated with reduced inflammation and less depression: a preliminary investigation. Obes Surg 2007; 17: 759-63; http://dx.doi.org/10.1007/s11695-007-9140-0
Alexopoulos GS. The vascular depression hypothesis: 10 years later. Biol Psychiatry 2006; 60: 1304-5; http://dx.doi.org/10.1016/j.biopsych.2006.09.006
Fenn AM, Gensel JC, Huang Y, et al. Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia. Biol Psychiatry 2013; 76: 575-84; http://dx.doi.org/10.1016/j.biopsych.2013.10.014
Hackett ML, Anderson CS. Predictors of depression after stroke: a systematic review of observational studies. Stroke 2005; 36: 2296-301; http://dx.doi.org/10.1161/01.STR.0000183622.75135.a4
Linden T, Blomstrand C, Skoog I. Depressive disorders after 20 months in elderly stroke patients. A case-control study. Stroke 2007; 38: 1860-3; http://dx.doi.org/10.1161/STROKEAHA.106.471805
Jorge RE, Robinson RG, Arndt S, et al. Mortality and poststroke depression: a placebo-controlled trial of antidepressants. Am J Psychiatry 2003; 160: 1823-9; http://dx.doi.org/10.1176/appi.ajp.160.10.1823
Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10: 1387-94; http://dx.doi.org/10.1038/nn1997
Wakselman S, Béchade C, Roumier A, et al. Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J Neurosci 2008; 28: 8138-43; http://dx.doi.org/10.1523/JNEUROSCI.1006-08.2008
Badan I, Platt D, Kessler C, et al. Temporal dynamics of degenerative and regenerative events associated with cerebral ischemia in aged rats. Gerontology 2003; 49: 356-65; http://dx.doi.org/10.1159/000073763
Buga AM, Scholz CJ, Kumar S, et al. Identification of new therapeutic targets by genome-wide analysis of gene expression in the ipsilateral cortex of aged rats after stroke. PLoS One 2012; 7: e50985; http://dx.doi.org/10.1371/journal.pone.0050985
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