PMID- 29766029
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 9
DP  - 2018 Jun 15
TI  - Seizure-Suppressant and Neuroprotective Effects of Encapsulated BDNF-Producing 
      Cells in a Rat Model of Temporal Lobe Epilepsy.
PG  - 211-224
LID - 10.1016/j.omtm.2018.03.001 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic 
      epilepsy, but evaluating its potential is complicated by difficulties in its 
      delivery to the brain. Here, we describe the effects on epileptic seizures of 
      encapsulated cell biodelivery (ECB) devices filled with genetically modified 
      human cells engineered to release BDNF. These devices, implanted into the 
      hippocampus of pilocarpine-treated rats, highly decreased the frequency of 
      spontaneous seizures by more than 80%. These benefits were associated with 
      improved cognitive performance, as epileptic rats treated with BDNF performed 
      significantly better on a novel object recognition test. Importantly, long-term 
      BDNF delivery did not alter normal behaviors such as general activity or 
      sleep/wake patterns. Detailed immunohistochemical analyses revealed that the 
      neurological benefits of BDNF were associated with several anatomical changes, 
      including reduction in degenerating cells and normalization of hippocampal 
      volume, neuronal counts (including parvalbumin-positive interneurons), and 
      neurogenesis. In conclusion, the present data suggest that BDNF, when 
      continuously released in the epileptic hippocampus, reduces the frequency of 
      generalized seizures, improves cognitive performance, and reverts many 
      histological alterations associated with chronic epilepsy. Thus, ECB 
      device-mediated long-term supplementation of BDNF in the epileptic tissue may 
      represent a valid therapeutic strategy against epilepsy and some of its 
      co-morbidities.
FAU - Falcicchia, Chiara
AU  - Falcicchia C
AD  - Department of Medical Science, Section of Pharmacology, Neuroscience Center, 
      University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
AD  - NsGene Inc., Providence, RI, USA.
FAU - Paolone, Giovanna
AU  - Paolone G
AD  - Department of Medical Science, Section of Pharmacology, Neuroscience Center, 
      University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
AD  - NsGene Inc., Providence, RI, USA.
FAU - Emerich, Dwaine F
AU  - Emerich DF
AD  - NsGene Inc., Providence, RI, USA.
FAU - Lovisari, Francesca
AU  - Lovisari F
AD  - Department of Medical Science, Section of Pharmacology, Neuroscience Center, 
      University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
FAU - Bell, William J
AU  - Bell WJ
AD  - NsGene Inc., Providence, RI, USA.
FAU - Fradet, Tracie
AU  - Fradet T
AD  - NsGene Inc., Providence, RI, USA.
FAU - Wahlberg, Lars U
AU  - Wahlberg LU
AD  - NsGene Inc., Providence, RI, USA.
FAU - Simonato, Michele
AU  - Simonato M
AD  - Department of Medical Science, Section of Pharmacology, Neuroscience Center, 
      University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.
AD  - School of Medicine, University Vita-Salute San Raffaele, Milan, Italy.
LA  - eng
PT  - Journal Article
DEP - 20180309
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC5948312
OTO - NOTNLM
OT  - BDNF
OT  - ECB devices
OT  - cell encapsulation
OT  - epilepsy
OT  - hippocampus
OT  - neurogenesis
EDAT- 2018/05/17 06:00
MHDA- 2018/05/17 06:01
PMCR- 2018/03/09
CRDT- 2018/05/17 06:00
PHST- 2017/12/20 00:00 [received]
PHST- 2018/03/05 00:00 [accepted]
PHST- 2018/05/17 06:00 [entrez]
PHST- 2018/05/17 06:00 [pubmed]
PHST- 2018/05/17 06:01 [medline]
PHST- 2018/03/09 00:00 [pmc-release]
AID - S2329-0501(18)30025-1 [pii]
AID - 10.1016/j.omtm.2018.03.001 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2018 Mar 9;9:211-224. doi: 10.1016/j.omtm.2018.03.001. 
      eCollection 2018 Jun 15.