PMID- 29611441
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20191201
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 38
IP  - 12
DP  - 2018 Dec
TI  - Juvenile cerebral ischemia reveals age-dependent BDNF-TrkB signaling changes: 
      Novel mechanism of recovery and therapeutic intervention.
PG  - 2223-2235
LID - 10.1177/0271678X18766421 [doi]
AB  - Global ischemia in childhood often leads to poor neurologic outcomes, including 
      learning and memory deficits. Using our novel model of childhood cardiac 
      arrest/cardiopulmonary resuscitation (CA/CPR), we investigate the mechanism of 
      ischemia-induced cognitive deficits and recovery. Memory is impaired seven days 
      after juvenile CA/CPR and completely recovers by 30 days. Consistent with this 
      remarkable recovery not observed in adults, hippocampal long-term potentiation 
      (LTP) is impaired 7-14 days after CA/CPR, recovering by 30 days. This recovery is 
      not due to the replacement of dead neurons (neurogenesis), but rather correlates 
      with brain-derived neurotrophic factor (BDNF) expression, implicating BDNF as the 
      molecular mechanism underlying impairment and recovery. Importantly, delayed 
      activation of TrkB receptor signaling reverses CA/CPR-induced LTP deficits and 
      memory impairments. These data provide two new insights (1) endogenous recovery 
      of memory and LTP through development may contribute to improved neurological 
      outcome in children compared to adults and (2) BDNF-enhancing drugs speed 
      recovery from pediatric cardiac arrest during the critical school ages.
FAU - Dietz, Robert M
AU  - Dietz RM
AD  - 1 Department of Pediatrics, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Orfila, James E
AU  - Orfila JE
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Rodgers, Krista M
AU  - Rodgers KM
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Patsos, Olivia P
AU  - Patsos OP
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Deng, Guiying
AU  - Deng G
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Chalmers, Nicholas
AU  - Chalmers N
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Quillinan, Nidia
AU  - Quillinan N
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 4 Department of Pharmacology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Traystman, Richard J
AU  - Traystman RJ
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 4 Department of Pharmacology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Herson, Paco S
AU  - Herson PS
AD  - 2 Neuronal Injury Program, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 3 Department of Anesthesiology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
AD  - 4 Department of Pharmacology, 129263 University of Colorado School of Medicine, 
      Aurora, CO, USA.
LA  - eng
GR  - K08 NS097586/NS/NINDS NIH HHS/United States
GR  - R01 GM125095/GM/NIGMS NIH HHS/United States
GR  - R01 NS092645/NS/NINDS NIH HHS/United States
GR  - R01 NS046072/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180403
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - EC 2.7.10.1 (Ntrk2 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
MH  - Animals
MH  - Brain Ischemia/*metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Male
MH  - Membrane Glycoproteins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuronal Plasticity/physiology
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Recovery of Function/*physiology
MH  - Signal Transduction/physiology
PMC - PMC6282214
OTO - NOTNLM
OT  - Global ischemia
OT  - brain-derived neurotrophic factor
OT  - hippocampus
OT  - memory and cognition
OT  - synaptic plasticity
EDAT- 2018/04/04 06:00
MHDA- 2019/08/06 06:00
PMCR- 2019/12/01
CRDT- 2018/04/04 06:00
PHST- 2018/04/04 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2018/04/04 06:00 [entrez]
PHST- 2019/12/01 00:00 [pmc-release]
AID - 10.1177_0271678X18766421 [pii]
AID - 10.1177/0271678X18766421 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2018 Dec;38(12):2223-2235. doi: 
      10.1177/0271678X18766421. Epub 2018 Apr 3.