TY  - JOUR
A1  - Cacheaux, Luisa P.
A1  - Ivens, Sebastian
A1  - David, Yaron
A1  - Lakhter, Alexander J.
A1  - Bar-Klein, Guy
A1  - Shapira, Michael
A1  - Heinemann, Uwe
A1  - Friedman, Alon
A1  - Kaufer, Daniela
T1  - Transcriptome Profiling Reveals TGF-β Signaling Involvement in Epileptogenesis
Y1  - 2009/07/15 
JF  - The Journal of Neuroscience 
JO  - The Journal of Neuroscience 
SP  - 8927 
EP  - 8935 
DO  - 10.1523/JNEUROSCI.0430-09.2009 
VL  - 29 
IS  - 28 
UR  - http://www.jneurosci.org/content/29/28/8927.abstract 
N2  - Brain injury may result in the development of epilepsy, one of the most common neurological disorders. We previously demonstrated that albumin is critical in the generation of epilepsy after blood–brain barrier (BBB) compromise. Here, we identify TGF-β pathway activation as the underlying mechanism. We demonstrate that direct activation of the TGF-β pathway by TGF-β1 results in epileptiform activity similar to that after exposure to albumin. Coimmunoprecipitation revealed binding of albumin to TGF-β receptor II, and Smad2 phosphorylation confirmed downstream activation of this pathway. Transcriptome profiling demonstrated similar expression patterns after BBB breakdown, albumin, and TGF-β1 exposure, including modulation of genes associated with the TGF-β pathway, early astrocytic activation, inflammation, and reduced inhibitory transmission. Importantly, TGF-β pathway blockers suppressed most albumin-induced transcriptional changes and prevented the generation of epileptiform activity. Our present data identifies the TGF-β pathway as a novel putative epileptogenic signaling cascade and therapeutic target for the prevention of injury-induced epilepsy. 
ER  -