PMID- 20610036
OWN - NLM
STAT- MEDLINE
DCOM- 20110304
LR  - 20161125
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 169
IP  - 1
DP  - 2010 Aug 11
TI  - Induction of striatal neurogenesis enhances functional recovery in an adult 
      animal model of neonatal hypoxic-ischemic brain injury.
PG  - 259-68
LID - 10.1016/j.neuroscience.2010.04.038 [doi]
AB  - While intraventricular administration of epidermal growth factor (EGF) expands 
      the proliferation of neural stem/progenitor cells in the subventricular zone 
      (SVZ), overexpression of brain-derived neurotrophic factor (BDNF) is particularly 
      effective in enhancing striatal neurogenesis. We assessed the induction of 
      striatal neurogenesis and consequent functional recovery after chronic infusion 
      of BDNF and EGF in an adult animal model of neonatal hypoxic-ischemic (HI) brain 
      injury. Permanent brain damage was induced in CD-1 (ICR) mice (P7) by applying 
      the ligation of unilateral carotid artery and hypoxic condition. At 6 weeks of 
      age, the mice were randomly assigned to groups receiving a continuous 2-week 
      infusion of one of the following treatments into the ventricle: BDNF, EGF, 
      BDNF/EGF, or phosphate buffered saline (PBS). Two weeks after treatment, 
      immunohistochemical analysis revealed an increase in the number of BrdU(+) cells 
      in the SVZ and striata of BDNF/EGF-treated mice. The number of new neurons 
      co-stained with BrdU and betaIII-tubulin was also significantly increased in the 
      neostriata of BDNF/EGF-treated mice, compared with PBS group. In addition, the 
      newly generated cells were expressed as migrating neuroblasts labeled with 
      PSA-NCAM or doublecortin in the SVZ and the ventricular side of neostriata. The 
      new striatal neurons were also differentiated as mature neurons co-labeled with 
      BrdU(+)/NeuN(+). When evaluated post-surgical 8 weeks, BDNF/EGF-treated mice 
      exhibited significantly longer rotarod latencies at constant speed (48 rpm) and 
      under accelerating condition (4-80 rpm), relative to PBS and untreated controls. 
      In the forelimb-use asymmetry test, BDNF/EGF-treated mice showed significant 
      improvement in the use of the contralateral forelimb. In contrast, this 
      BDNF/EGF-associated functional recovery was abolished in mice receiving a 
      co-infusion of 2% cytosine-b-d-arabinofuranoside (Ara-C), a mitotic inhibitor. 
      Induction of striatal neurogenesis by the intraventricular administration of BDNF 
      and EGF promoted functional recovery in an adult animal model of neonatal HI 
      brain injury. The effect of Ara-C to completely block functional recovery 
      indicates that the effect may be the result of newly generated neurons. 
      Therefore, this treatment may offer a promising strategy for the restoration of 
      motor function for adults with cerebral palsy (CP).
CI  - Published by Elsevier Ltd.
FAU - Im, S H
AU  - Im SH
AD  - Department and Research Institute of Rehabilitation Medicine, Yonsei University 
      College of Medicine, Seoul, South Korea.
FAU - Yu, J H
AU  - Yu JH
FAU - Park, E S
AU  - Park ES
FAU - Lee, J E
AU  - Lee JE
FAU - Kim, H O
AU  - Kim HO
FAU - Park, K I
AU  - Park KI
FAU - Kim, G W
AU  - Kim GW
FAU - Park, C I
AU  - Park CI
FAU - Cho, S-R
AU  - Cho SR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 04079A1RDZ (Cytarabine)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Ataxia/drug therapy/etiology/physiopathology
MH  - Brain Damage, Chronic/etiology/*prevention & control
MH  - Brain-Derived Neurotrophic Factor/administration & 
      dosage/pharmacology/*therapeutic use
MH  - Carotid Arteries
MH  - Cerebral Palsy
MH  - Corpus Striatum/drug effects/*physiopathology
MH  - Cytarabine/pharmacology
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Epidermal Growth Factor/administration & dosage/pharmacology/therapeutic use
MH  - Forelimb/physiopathology
MH  - Hemiplegia/drug therapy/etiology/physiopathology
MH  - Hypoxia/complications
MH  - Hypoxia-Ischemia, Brain/*drug therapy/physiopathology
MH  - Infusions, Intraventricular
MH  - Ligation
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Neurogenesis/*drug effects
MH  - Random Allocation
MH  - Recovery of Function
EDAT- 2010/07/09 06:00
MHDA- 2011/03/05 06:00
CRDT- 2010/07/09 06:00
PHST- 2009/08/06 00:00 [received]
PHST- 2010/04/03 00:00 [revised]
PHST- 2010/04/19 00:00 [accepted]
PHST- 2010/07/09 06:00 [entrez]
PHST- 2010/07/09 06:00 [pubmed]
PHST- 2011/03/05 06:00 [medline]
AID - S0306-4522(10)00581-6 [pii]
AID - 10.1016/j.neuroscience.2010.04.038 [doi]
PST - ppublish
SO  - Neuroscience. 2010 Aug 11;169(1):259-68. doi: 10.1016/j.neuroscience.2010.04.038.