PMID- 24551199
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20240322
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - TrkB agonist antibody pretreatment enhances neuronal survival and long-term 
      sensory motor function following hypoxic ischemic injury in neonatal rats.
PG  - e88962
LID - 10.1371/journal.pone.0088962 [doi]
LID - e88962
AB  - Perinatal hypoxic ischemia (H-I) causes brain damage and long-term neurological 
      impairments, leading to motor dysfunctions and cerebral palsy. Many studies have 
      demonstrated that the TrkB-ERK1/2 signaling pathway plays a key role in mediating 
      the protective effect of brain-derived neurotrophic factor (BDNF) following 
      perinatal H-I brain injury in experimental animals. In the present study, we 
      explored the neuroprotective effects of the TrkB-specific agonist monoclonal 
      antibody 29D7 on H-I brain injury in neonatal rats. First, we found that 
      intracerebroventricular (icv) administration of 29D7 in normal P7 rats markedly 
      increased the levels of phosphorylated ERK1/2 and phosphorylated AKT in neurons 
      up to 24 h. Second, P7 rats received icv administration of 29D7 and subjected to 
      H-I injury induced by unilateral carotid artery ligation and exposure to hypoxia 
      (8% oxygen). We found that 29D7, to a similar extent to BDNF, significantly 
      inhibited activation of caspase-3, a biochemical hallmark of apoptosis, following 
      H-I injury. Third, we found that this 29D7-mediated neuroprotective action 
      persisted at least up to 5 weeks post-H-I injury as assessed by brain tissue 
      loss, implicating long-term neurotrophic effects rather than an acute delay of 
      cell death. Moreover, the long-term neuroprotective effect of 29D7 was tightly 
      correlated with sensorimotor functional recovery as assessed by a tape-removal 
      test, while 29D7 did not significantly improve rotarod performance. Taken 
      together, these findings demonstrate that pretreatment with the TrkB-selective 
      agonist 29D7 significantly increases neuronal survival and behavioral recovery 
      following neonatal hypoxic-ischemic brain injury.
FAU - Kim, Gab Seok
AU  - Kim GS
AD  - Department of Pharmacology, Seoul National University, College of Pharmacy, 
      Seoul, Republic of Korea.
FAU - Cho, Seongeun
AU  - Cho S
AD  - Wyeth Neuroscience Discovery Research, Princeton, New Jersey, United States of 
      America.
FAU - Nelson, James W
AU  - Nelson JW
AD  - Department of Neurological Surgery Washington University School of Medicine, St. 
      Louis, Missouri, United States of America ; Hope Center for Neurological 
      Disorders Washington University School of Medicine, St. Louis, Missouri, United 
      States of America.
FAU - Zipfel, Gregory J
AU  - Zipfel GJ
AD  - Department of Neurological Surgery Washington University School of Medicine, St. 
      Louis, Missouri, United States of America ; Hope Center for Neurological 
      Disorders Washington University School of Medicine, St. Louis, Missouri, United 
      States of America ; Department of Neurology, Washington University School of 
      Medicine, St. Louis, Missouri, United States of America.
FAU - Han, Byung Hee
AU  - Han BH
AD  - Department of Pharmacology, Seoul National University, College of Pharmacy, 
      Seoul, Republic of Korea ; Department of Neurological Surgery Washington 
      University School of Medicine, St. Louis, Missouri, United States of America ; 
      Hope Center for Neurological Disorders Washington University School of Medicine, 
      St. Louis, Missouri, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140214
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies/administration & dosage/*pharmacology
MH  - Body Temperature/drug effects
MH  - Caspase 3/metabolism
MH  - Cell Survival/drug effects
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Hypoxia-Ischemia, Brain/drug therapy/enzymology/*pathology/physiopathology
MH  - Injections, Intraventricular
MH  - Male
MH  - Motor Activity/*drug effects
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*agonists/metabolism
MH  - Sensory Receptor Cells/drug effects/enzymology/*pathology
PMC - PMC3925177
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/02/20 06:00
MHDA- 2014/10/22 06:00
PMCR- 2014/02/14
CRDT- 2014/02/20 06:00
PHST- 2013/09/13 00:00 [received]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/02/20 06:00 [entrez]
PHST- 2014/02/20 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
PHST- 2014/02/14 00:00 [pmc-release]
AID - PONE-D-13-37662 [pii]
AID - 10.1371/journal.pone.0088962 [doi]
PST - epublish
SO  - PLoS One. 2014 Feb 14;9(2):e88962. doi: 10.1371/journal.pone.0088962. eCollection 
      2014.