{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:36:08Z","timestamp":1771338968798,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T00:00:00Z","timestamp":1447804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["456615\/2013-0"],"award-info":[{"award-number":["456615\/2013-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["34\/204.823\/2014"],"award-info":[{"award-number":["34\/204.823\/2014"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tissue plasminogen activator (tPA) mediates a number of processes that are pivotal for synaptogenesis and remodeling of synapses, including proteolysis of the brain extracellular matrix, degradation of adhesion molecules, activation of neurotrophins, and activation of the N-methyl-d-aspartate receptor. Abnormalities in these processes have been consistently described in psychotic disorders. In this paper, we review the physiological roles of tPA, focusing on conditions characterized by low tPA activity, which are prevalent in schizophrenia. We then describe how tPA activity is influenced by lifestyle interventions and nutritional supplements that may ameliorate psychotic symptoms. Next, we analyze the role of tPA in the mechanism of action of hormones and medications effective in mitigating psychotic symptoms, such as pregnenolone, estrogen, oxytocin, dopamine D3 receptor antagonists, retinoic acid, valproic acid, cannabidiol, sodium nitroprusside, N-acetyl cysteine, and warfarin. We also review evidence that tPA participates in the mechanism by which electroconvulsive therapy and cigarette smoking may reduce psychotic symptoms.<\/jats:p>","DOI":"10.3390\/ijms161126053","type":"journal-article","created":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T10:35:12Z","timestamp":1447842912000},"page":"27550-27560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Improvement of Psychotic Symptoms and the Role of Tissue Plasminogen Activator"],"prefix":"10.3390","volume":"16","author":[{"given":"Silvia","family":"Hoirisch-Clapauch","sequence":"first","affiliation":[{"name":"Department of Hematology, Hospital Federal dos Servidores do Estado, Ministry of Health, Rio de Janeiro CEP 20221-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-4669","authenticated-orcid":false,"given":"Antonio","family":"Nardi","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Federal University of Rio de Janeiro, and National Institute for Translational Medicine, INCT-TM CEP 22290-140, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1160\/TH13-06-0517","article-title":"Human tissue-type plasminogen activator","volume":"112","author":"Kruithof","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1523\/JNEUROSCI.16-07-02220.1996","article-title":"Membrane depolarization induces calcium dependent secretion of tissue plasminogen activator","volume":"16","author":"Gualandris","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.brainres.2011.06.042","article-title":"Serine proteases, serine protease inhibitors, and protease-activated receptors: roles in synaptic function and behavior","volume":"1407","author":"Almonte","year":"2011","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e106238","DOI":"10.1371\/journal.pone.0106238","article-title":"Subacute intranasal administration of tissue plasminogen activator promotes neuroplasticity and improves functional recovery following traumatic brain injury in rats","volume":"9","author":"Meng","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1515\/revneuro-2013-0007","article-title":"Does extracellular proteolysis control mammalian cognition?","volume":"24","author":"Tamura","year":"2013","journal-title":"Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1001\/jamapsychiatry.2013.155","article-title":"Schizophrenia is a cognitive illness: Time for a change in focus","volume":"70","author":"Kahn","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/wps.20145","article-title":"Cognitive impairments in psychotic disorders: Common mechanisms and measurement","volume":"13","author":"Barch","year":"2014","journal-title":"World Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/83358","article-title":"The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling","volume":"7","author":"Nicole","year":"2001","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0166-2236(02)00040-1","article-title":"The Yin and Yang of NMDA receptor signalling","volume":"26","author":"Hardingham","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_10","unstructured":"Lu, B., Nagappan, G., and Lu, Y. (2014). Handbook of Experimental Pharmacology, Springer Berlin Heidelberg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1124\/mol.106.022467","article-title":"Involvement of tissue plasminogen activator-plasmin system in depolarization-evoked dopamine release in the nucleus accumbens of mice","volume":"70","author":"Ito","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1111\/j.1538-7836.2005.01420.x","article-title":"PAI-1 and atherothrombosis","volume":"3","author":"Vaughan","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1182\/blood-2012-06-436188","article-title":"Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation","volume":"120","author":"Huang","year":"2012","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.molbrainres.2003.12.018","article-title":"Neuroserpin is post-transcriptionally regulated by thyroid hormone","volume":"123","author":"Cuadrado","year":"2004","journal-title":"Mol. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2741\/1778","article-title":"Neuroserpin","volume":"11","author":"Galliciotti","year":"2006","journal-title":"Front. Biosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/bjh.12627","article-title":"Prevalence of antiphospholipid antibodies in psychiatric patients users and non-users of antipsychotics","volume":"164","author":"Delluc","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.pnpbp.2008.09.009","article-title":"Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia","volume":"32","author":"Piperski","year":"2008","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.schres.2014.07.033","article-title":"Serum levels of BDNF, folate and homocysteine: In relation to hippocampal volume and psychopathology in drug na\u00efve, first episode schizophrenia","volume":"159","author":"Song","year":"2014","journal-title":"Schizophr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1055\/s-0033-1334143","article-title":"Annexin A2 system in human biology: Cell surface and beyond","volume":"39","author":"Luo","year":"2013","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.schres.2014.08.011","article-title":"Markers of low activity of tissue plasminogen activator\/plasmin are prevalent in schizophrenia patients","volume":"159","author":"Nardi","year":"2014","journal-title":"Schizophr. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.psychres.2006.02.002","article-title":"Reduced anticardiolipin antibodies in first episode and chronic schizophrenia","volume":"144","author":"Sirota","year":"2006","journal-title":"Psychiatry Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1440-1819.2008.01886.x","article-title":"Effects of a 10-week weight control program on obese patients with schizophrenia or schizoaffective disorder: A 12-month follow up","volume":"63","author":"Chen","year":"2009","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-7075-6-10","article-title":"Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: A case report and review of the literature","volume":"6","author":"Kraft","year":"2009","journal-title":"Nutr. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1001\/archgenpsychiatry.2009.193","article-title":"Hippocampal plasticity in response to exercise in schizophrenia","volume":"67","author":"Pajonk","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.physbeh.2014.11.054","article-title":"Antidepressant-like effect of n-3 PUFAs in CUMS rats: Role of tPA\/PAI-1 system","volume":"139","author":"Tang","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/0002-8703(88)90440-1","article-title":"Reduction in plasminogen activator inhibitor-1 (PAI-1) with omega-3 potyunsaturated fatty acid (PUFA) intake","volume":"116","author":"Mehta","year":"1988","journal-title":"Am. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1210\/en.2007-1722","article-title":"Obesity and hypertriglyceridemia produce cognitive impairment","volume":"149","author":"Farr","year":"2008","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7934","DOI":"10.1038\/ncomms8934","article-title":"Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study","volume":"6","author":"Amminger","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.biopsych.2005.10.009","article-title":"Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia","volume":"60","author":"Levine","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12881-015-0197-7","article-title":"Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis","volume":"16","author":"Numata","year":"2015","journal-title":"BMC Med. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0166-2236(03)00032-8","article-title":"Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders","volume":"26","author":"Mattson","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fnins.2013.00157","article-title":"Pgrmc1: New roles in the microglial mediation of progesterone-antagonism of estradiol-dependent neurite sprouting and in microglial activation","volume":"7","author":"Bali","year":"2013","journal-title":"Front. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/frne.1999.0188","article-title":"Neurosteroids: Biosynthesis and function of these novel neuromodulators","volume":"21","author":"Compagnone","year":"2000","journal-title":"Front. Neuroendocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1210\/en.2007-1050","article-title":"Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone\u2019s antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations","volume":"149","author":"Peluso","year":"2008","journal-title":"Endocrinology"},{"key":"ref_35","first-page":"917901","article-title":"Progesterone and cerebral function during emotion processing in men and women with schizophrenia","volume":"2012","author":"Champagne","year":"2012","journal-title":"Schizophr. Res. Treat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/pcn.12150","article-title":"Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: An 8-week, double-blind, randomized add-on two-center trial","volume":"68","author":"Ritsner","year":"2014","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1038\/npp.2009.26","article-title":"Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia","volume":"34","author":"Marx","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.pbb.2006.07.026","article-title":"Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: Candidate mechanism for superior efficacy?","volume":"84","author":"Marx","year":"2006","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1161\/01.RES.0000136521.70093.f1","article-title":"Differential and opposing regulation of PAI-1 promoter activity by estrogen receptor \u03b1 and estrogen receptor \u03b2 in endothelial cells","volume":"95","author":"Smith","year":"2004","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1177\/1073858413519865","article-title":"Estrogen receptors, the hippocampus, and memory","volume":"20","author":"Bean","year":"2014","journal-title":"Neuroscientist"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/mp.2014.33","article-title":"Estradiol for treatment-resistant schizophrenia: A large-scale randomized-controlled trial in women of child-bearing age","volume":"20","author":"Kulkarni","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Da Silva, T.L., and Ravindran, A.V. (2015). Contribution of sex hormones to gender differences in schizophrenia: A review. Asian J. Psychiatry.","DOI":"10.1016\/j.ajp.2015.07.016"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0028-2243(94)90032-9","article-title":"Effects of labor and delivery on fibrinolysis","volume":"55","author":"Bremer","year":"1994","journal-title":"Eur. J. Obst. Gynecol. Reprod. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.schres.2011.07.027","article-title":"Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia","volume":"132","author":"Pedersen","year":"2011","journal-title":"Schizophr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/347146a0","article-title":"Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics","volume":"347","author":"Sokoloff","year":"1990","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.neuroscience.2013.07.053","article-title":"Dopamine D3 receptor deletion increases tissue plasminogen activator (tPA) activity in prefrontal cortex and hippocampus","volume":"250","author":"Castorina","year":"2013","journal-title":"Neuroscience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.euroneuro.2015.07.012","article-title":"Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective agents","volume":"25","author":"Pich","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/sj.mp.4001668","article-title":"Microarray results suggest altered transport and lowered synthesis of retinoic acid in schizophrenia","volume":"10","author":"Goodman","year":"2005","journal-title":"Mol. Psychiatry"},{"key":"ref_49","first-page":"113","article-title":"Species-specific regulation of t-PA and PAI-1 gene expression in human and rat astrocytes","volume":"8","author":"Hultman","year":"2014","journal-title":"Gene Regul. Syst. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1055\/s-0038-1648191","article-title":"Stimulation of tissue-type plasminogen activator synthesis by retinoids in cultured human endothelial cells and rat tissues in vivo","volume":"65","author":"Kooistra","year":"1991","journal-title":"Thromb. Haemost."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1002\/hipo.22037","article-title":"Patterning of retinoic acid signaling and cell proliferation in the hippocampus","volume":"22","author":"Goodman","year":"2012","journal-title":"Hippocampus"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.4088\/JCP.12m08160","article-title":"The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: A 6-week, randomized, double-blind, placebo-controlled multicenter trial","volume":"74","author":"Lerner","year":"2013","journal-title":"J. Clin. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/glia.22463","article-title":"Valproic acid induces astrocyte-dependent neurite outgrowth from cultured rat primary cortical neuron via modulation of tPA\/PAI-1 activity","volume":"61","author":"Cho","year":"2013","journal-title":"Glia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e31573","DOI":"10.1371\/journal.pone.0031573","article-title":"Role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression","volume":"7","author":"Larsson","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1007\/s11095-010-0219-2","article-title":"Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells","volume":"27","author":"Ramer","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1038\/tp.2012.15","article-title":"Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia","volume":"2","author":"Leweke","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1001\/jamapsychiatry.2013.210","article-title":"Nitric oxide and symptom reduction in schizophrenia","volume":"70","author":"Coyle","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1161\/01.HYP.0000260471.16113.d8","article-title":"Nitric oxide modulates tissue plasminogen activator release in normotensive subjects and hypertensive patients","volume":"49","author":"Giannarelli","year":"2007","journal-title":"Hypertension"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/JCP.0000000000000258","article-title":"The effects of sodium nitroprusside treatment on cognitive deficits in schizophrenia: a pilot study","volume":"35","author":"Abrao","year":"2015","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1161\/01.CIR.0000163542.48611.A2","article-title":"Tissue-type plasminogen activator crosses the intact blood\u2013brain barrier by low-density lipoprotein receptor\u2013related protein-mediated transcytosis","volume":"111","author":"Benchenane","year":"2005","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.mehy.2012.11.011","article-title":"Psychiatric remission with warfarin: Should psychosis be addressed as plasminogen activator imbalance?","volume":"80","author":"Nardi","year":"2013","journal-title":"Med. Hypotheses"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/clpt.2009.95","article-title":"Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium","volume":"86","author":"Anthony","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1016\/j.ijcard.2011.07.058","article-title":"Warfarin resistance and caffeine containing beverages","volume":"156","author":"Clapauch","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.biopsych.2008.03.004","article-title":"N-Acetyl cysteine as a glutathione precursor for schizophrenia\u2014A double-blind, randomized, placebo-controlled trial","volume":"64","author":"Berk","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0140-6736(91)92161-T","article-title":"Lipoprotein (a) reduction by N-acetylcysteine","volume":"337","author":"Gavish","year":"1991","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/S0735-1097(02)01797-7","article-title":"N-acetylcysteine in acute cardiology: 10 years later: What do we know and what would we like to know?","volume":"39","author":"Sochman","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1016\/S0021-9258(18)52266-3","article-title":"Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. A potential mechanism in thrombogenesis","volume":"266","author":"Etingin","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_68","unstructured":"Parmer, R.J., Mahata, S.K., Jiang, Q., Taupenot, L., Gong, Y., Mahata, M., O\u2019Connor, D.T., and Miles, L.A. (2002). Chromogranins, Springer."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1213\/00000539-199111000-00009","article-title":"Prevention of the cardiovascular and neuroendocrine response to electroconvulsive therapy: II. Effects of pretreatment regimens on catecholamines, ACTH, vasopressin, and cortisol","volume":"73","author":"Weinger","year":"1991","journal-title":"Anesth. Analg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1017\/S1461145712000053","article-title":"Electroconvulsive seizure, but not imipramine, rapidly up-regulates pro-BDNF and t-PA, leading to mature BDNF production, in the rat hippocampus","volume":"16","author":"Segawa","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/0269881113507639","article-title":"Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy","volume":"28","author":"Mezzasalma","year":"2014","journal-title":"J. Psychopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.schres.2013.02.005","article-title":"Indications for electroconvulsive treatment in schizophrenia: A systematic review","volume":"146","author":"Pompili","year":"2013","journal-title":"Schizophr. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3109\/15622975.2011.564653","article-title":"Using ECT in schizophrenia: A review from a clinical perspective","volume":"13","author":"Zervas","year":"2012","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1254\/jphs.08R04FM","article-title":"Basic and translational research on proteinase-activated receptors: Regulation of nicotine reward by the tissue plasminogen activator (tPA)-plasmin system via proteinase-activated receptor 1","volume":"108","author":"Nagai","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.comppsych.2014.11.024","article-title":"Assessment of cigarette smoking status with respect to symptomatic manifestation in first-episode schizophrenia patients","volume":"58","author":"Misiak","year":"2015","journal-title":"Compr. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1093\/ntr\/ntu163","article-title":"Cognitive effects of very low nicotine content cigarettes, with and without nicotine replacement, in smokers with schizophrenia and controls","volume":"17","author":"AhnAllen","year":"2015","journal-title":"Nicotine Tob. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/00004647-200003000-00002","article-title":"Reduction of tissue plasminogen activator-induced hemorrhage and brain injury by free radical spin trapping after embolic focal cerebral ischemia in rats","volume":"20","author":"Asahi","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_78","first-page":"355","article-title":"Rituximab treatment for resistant antiphospholipid syndrome","volume":"33","author":"Rubenstein","year":"2006","journal-title":"J. Rheumatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/11\/26053\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:52:17Z","timestamp":1760215937000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/11\/26053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,18]]},"references-count":78,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,11]]}},"alternative-id":["ijms161126053"],"URL":"https:\/\/doi.org\/10.3390\/ijms161126053","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,18]]}}}