PMID- 24118418
OWN - NLM
STAT- MEDLINE
DCOM- 20140716
LR  - 20131202
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 38
IP  - 11
DP  - 2013 Dec
TI  - Blocking brain-derived neurotrophic factor inhibits injury-induced 
      hyperexcitability of hippocampal CA3 neurons.
PG  - 3554-66
LID - 10.1111/ejn.12367 [doi]
AB  - Brain trauma can disrupt synaptic connections, and this in turn can prompt axons 
      to sprout and form new connections. If these new axonal connections are aberrant, 
      hyperexcitability can result. It has been shown that ablating tropomyosin-related 
      kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), can 
      reduce axonal sprouting after hippocampal injury. However, it is unknown whether 
      inhibiting BDNF-mediated axonal sprouting will reduce hyperexcitability. Given 
      this, our purpose here was to determine whether pharmacologically blocking BDNF 
      inhibits hyperexcitability after injury-induced axonal sprouting in the 
      hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic 
      hippocampal slice cultures. As reported by others, we observed a 50% reduction in 
      axonal sprouting in cultures treated with a BDNF blocker (TrkB-Fc) 14 days after 
      injury. Furthermore, lesioned cultures treated with TrkB-Fc were less 
      hyperexcitable than lesioned untreated cultures. Using electrophysiology, we 
      observed a two-fold decrease in the number of CA3 neurons that showed bursting 
      responses after lesion with TrkB-Fc treatment, whereas we found no change in 
      intrinsic neuronal firing properties. Finally, evoked field excitatory 
      postsynaptic potential recordings indicated an increase in network activity 
      within area CA3 after lesion, which was prevented with chronic TrkB-Fc treatment. 
      Taken together, our results demonstrate that blocking BDNF attenuates 
      injury-induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has 
      been found in patients with post-traumatic epilepsy. Therefore, our data suggest 
      that blocking the BDNF-TrkB signaling cascade shortly after injury may be a 
      potential therapeutic target for the treatment of post-traumatic epilepsy.
CI  - (c) 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Gill, Raminder
AU  - Gill R
AD  - Department of Pharmacology & Therapeutics, McGill University, Bellini Life 
      Sciences Complex, 3649 Promenade Sir William Osler, Montreal, QC, Canada, H3G 
      0B1.
FAU - Chang, Philip K-Y
AU  - Chang PK
FAU - Prenosil, George A
AU  - Prenosil GA
FAU - Deane, Emily C
AU  - Deane EC
FAU - McKinney, Rebecca A
AU  - McKinney RA
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130930
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
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)
SB  - IM
CIN - Eur J Neurosci. 2013 Dec;38(11):3552-3. doi: 10.1111/ejn.12419. PMID: 24289826
MH  - Animals
MH  - Axons/pathology
MH  - Brain Injuries/metabolism/*physiopathology
MH  - Brain-Derived Neurotrophic Factor/*deficiency
MH  - CA3 Region, Hippocampal/metabolism/pathology/*physiology
MH  - *Excitatory Postsynaptic Potentials
MH  - Membrane Glycoproteins/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Pyramidal Cells/metabolism/pathology/physiopathology
OTO - NOTNLM
OT  - GAP43
OT  - axonal sprouting
OT  - brain-derived neurotrophic factor
OT  - organotypic hippocampal slices
OT  - post-traumatic epilepsy
EDAT- 2013/10/15 06:00
MHDA- 2014/07/17 06:00
CRDT- 2013/10/15 06:00
PHST- 2011/10/21 00:00 [received]
PHST- 2013/08/16 00:00 [revised]
PHST- 2013/08/28 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2014/07/17 06:00 [medline]
AID - 10.1111/ejn.12367 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2013 Dec;38(11):3554-66. doi: 10.1111/ejn.12367. Epub 2013 Sep 
      30.