PMID- 10908618
OWN - NLM
STAT- MEDLINE
DCOM- 20000810
LR  - 20240420
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 15
DP  - 2000 Aug 1
TI  - BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK 
      pathway.
PG  - 5775-81
AB  - Neurotrophins activate several different intracellular signaling pathways that in 
      some way exert neuroprotective effects. In vitro studies of sympathetic and 
      cerebellar granule neurons have demonstrated that the survival effects of 
      neurotrophins can be mediated via activation of the phosphatidylinositol 3-kinase 
      (PI3-kinase) pathway. Neurotrophin-mediated protection of other neuronal types in 
      vitro can be mediated via the extracellular signal-related protein kinase (ERK) 
      pathway. Whether either of these pathways contributes to the neuroprotective 
      effects of neurotrophins in the brain in vivo has not been determined. 
      Brain-derived neurotrophic factor (BDNF) is markedly neuroprotective against 
      neonatal hypoxic-ischemic (H-I) brain injury in vivo. We assessed the role of the 
      ERK and PI3-kinase pathways in neonatal H-I brain injury in the presence and 
      absence of BDNF. Intracerebroventricular administration of BDNF to postnatal day 
      7 rats resulted in phosphorylation of ERK1/2 and the PI3-kinase substrate AKT 
      within minutes. Effects were greater on ERK activation and occurred in neurons. 
      Pharmacological inhibition of ERK, but not the PI3-kinase pathway, inhibited the 
      ability of BDNF to block H-I-induced caspase-3 activation and tissue loss. These 
      findings suggest that neuronal ERK activation in the neonatal brain mediates 
      neuroprotection against H-I brain injury, a model of cerebral palsy.
FAU - Han, B H
AU  - Han BH
AD  - Department of Neurology, Washington University School of Medicine, St. Louis, MO 
      63110, USA.
FAU - Holtzman, D M
AU  - Holtzman DM
LA  - eng
GR  - P50 NS035902/NS/NINDS NIH HHS/United States
GR  - NS 35902/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Androstadienes)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Butadienes)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitriles)
RN  - 0 (U 0126)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Butadienes/pharmacology
MH  - Caspase 3
MH  - Caspase Inhibitors
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Hippocampus/cytology/enzymology
MH  - Hypoxia-Ischemia, Brain/*drug therapy/*metabolism
MH  - Injections, Intraventricular
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neocortex/cytology/enzymology
MH  - Neurons/cytology/enzymology
MH  - Neuroprotective Agents/*pharmacology
MH  - Nitriles/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Wortmannin
PMC - PMC6772561
EDAT- 2000/07/26 11:00
MHDA- 2000/08/12 11:00
PMCR- 2001/02/01
CRDT- 2000/07/26 11:00
PHST- 2000/07/26 11:00 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 2000/07/26 11:00 [entrez]
PHST- 2001/02/01 00:00 [pmc-release]
AID - 20/15/5775 [pii]
AID - 4363 [pii]
AID - 10.1523/JNEUROSCI.20-15-05775.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 Aug 1;20(15):5775-81. doi: 10.1523/JNEUROSCI.20-15-05775.2000.