PMID- 26469350
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 10
DP  - 2015
TI  - Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of 
      Stroke Outcome. Impact of rt-PA Treatment.
PG  - e0140668
LID - 10.1371/journal.pone.0140668 [doi]
LID - e0140668
AB  - The recombinant form of tissue plasminogen activator (rt-PA) is the only curative 
      treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism 
      of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in 
      post-stroke neuroplasticity. Thus, the objective of our study was to investigate 
      the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans 
      and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at 
      hospital admission and at up to 90 days in stroke patients receiving (n = 24) or 
      not (n = 14) rt-PA perfusion. We investigated the relationships between serum 
      BDNF with concurrent t-PA/plasmin activity, neurological outcomes and 
      cardiovascular scores at admission. In parallel, serum BDNF levels and 
      t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction 
      of ischemic stroke in rats. Our study revealed higher serum BDNF levels and 
      better neurological outcome in rt-PA-treated than non-treated patients. However, 
      serum BDNF levels did not predict stroke outcome when the whole cohort of stroke 
      patients was analyzed. By contrast, serum BDNF levels when measured at admission 
      and at day 90 correlated with cardiovascular scores, and those at day 1 
      correlated with serum t-PA/plasmin activity in the whole cohort of patients 
      whereas no association could be found in the rt-PA-treated group. In rats devoid 
      of cardiovascular risk, no difference in post-stroke serum BDNF levels was 
      detected between rt-PA- and vehicle-treated animals and no correlation was found 
      between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest 
      that serum BDNF levels may not be useful as a prognostic biomarker of stroke 
      outcome and that endothelial dysfunction could be a confounding factor when serum 
      BDNF levels after stroke are used to reflect of brain BDNF levels.
FAU - Rodier, Marion
AU  - Rodier M
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, 
      F-21078, France; Universite de Bourgogne Franche-Comte, Dijon, F-21079, France; 
      Department of Neurology, University Hospital, Dijon, F-21000, France.
FAU - Quirie, Aurore
AU  - Quirie A
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, 
      F-21078, France; Universite de Bourgogne Franche-Comte, Dijon, F-21079, France; 
      Departement Genie Biologique, IUT, Dijon, F-21078, France.
FAU - Prigent-Tessier, Anne
AU  - Prigent-Tessier A
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, 
      F-21078, France; Universite de Bourgogne Franche-Comte, Dijon, F-21079, France.
FAU - Bejot, Yannick
AU  - Bejot Y
AD  - Department of Neurology, University Hospital, Dijon, F-21000, France; Centre 
      d'Epidemiologie des Populations, EA4184, Dijon, F-21000, France.
FAU - Jacquin, Agnes
AU  - Jacquin A
AD  - Department of Neurology, University Hospital, Dijon, F-21000, France; Centre 
      d'Epidemiologie des Populations, EA4184, Dijon, F-21000, France.
FAU - Mossiat, Claude
AU  - Mossiat C
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, 
      F-21078, France; Universite de Bourgogne Franche-Comte, Dijon, F-21079, France.
FAU - Marie, Christine
AU  - Marie C
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, 
      F-21078, France; Universite de Bourgogne Franche-Comte, Dijon, F-21079, France.
FAU - Garnier, Philippe
AU  - Garnier P
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, 
      F-21078, France; Universite de Bourgogne Franche-Comte, Dijon, F-21079, France; 
      Departement Genie Biologique, IUT, Dijon, F-21078, France.
LA  - eng
PT  - Journal Article
DEP - 20151015
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Fibrinolytic Agents)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Biomarkers/blood
MH  - Brain Ischemia/blood/*drug therapy
MH  - Brain-Derived Neurotrophic Factor/*blood
MH  - Female
MH  - Fibrinolytic Agents/*administration & dosage/blood/therapeutic use
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Perfusion
MH  - Prognosis
MH  - Rats
MH  - Stroke/blood/*drug therapy
MH  - Tissue Plasminogen Activator/*administration & dosage/blood/therapeutic use
MH  - Treatment Outcome
PMC - PMC4607484
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/10/16 06:00
MHDA- 2016/06/15 06:00
PMCR- 2015/10/15
CRDT- 2015/10/16 06:00
PHST- 2015/02/20 00:00 [received]
PHST- 2015/09/29 00:00 [accepted]
PHST- 2015/10/16 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
PHST- 2015/10/15 00:00 [pmc-release]
AID - PONE-D-15-07781 [pii]
AID - 10.1371/journal.pone.0140668 [doi]
PST - epublish
SO  - PLoS One. 2015 Oct 15;10(10):e0140668. doi: 10.1371/journal.pone.0140668. 
      eCollection 2015.