AU  - Cacheaux, Luisa P.
AU  - Ivens, Sebastian
AU  - David, Yaron
AU  - Lakhter, Alexander J.
AU  - Bar-Klein, Guy
AU  - Shapira, Michael
AU  - Heinemann, Uwe
AU  - Friedman, Alon
AU  - Kaufer, Daniela
TI  - Transcriptome Profiling Reveals TGF-β Signaling Involvement in Epileptogenesis
PT  - JOURNAL ARTICLE
DP  - 2009 Jul 15 
TA  - The Journal of Neuroscience 
PG  - 8927-8935 
VI  - 29 
IP  - 28 
4099 - http://www.jneurosci.org/content/29/28/8927.abstract 
4100 - http://www.jneurosci.org/content/29/28/8927.full 
SO - J. Neurosci. 2009 Jul 15; 29(28):8927-8935 
AID  - 10.1523/JNEUROSCI.0430-09.2009 [doi] 
AB  - 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.