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10.1002/ana.24147 http://scihub22266oqcxt.onion/10.1002/ana.24147 C4077937!4077937!24659129     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Ann+Neurol 2014 ; 75 (6): 864-75 Nephropedia Template TP {{tp|p=24659129|t=2014. Losartan prevents acquired epilepsy via TGF-? signaling suppression |pdf=|usr=}}{{24659129}} gab.com Text Losartan prevents acquired epilepsy via TGF- signaling suppression JO: Ann Neurol http://www.kidney.de/pget.php?&tw=1&pmid=24659129 #FOAvip Objective: Acquired epilepsy is frequently associated with structural lesions following trauma, stroke and infections. While seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor ? (TGF-?) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-? signaling and tested the efficacy of blocking the TGF-? pathway in preventing epilepsy. Methods: We addressed the role of TGF-? signaling in epiletogenesis in two different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, magnetic resonance and direct optical imaging for blood-brain barrier (BBB) permeability and vascular reactivity. Long-term electrocorticographic (ECoG) recordings were acquired in freely behaving animals. Results: We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 (ALK5) pathway of TGF-? receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist (AT1), losartan, previously identified as a blocker of peripheral TGF-? signaling, effectively blocks albumin-induced TGF-? activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation: TGF-? signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, an FDA-approved drug, as an efficient anti-epileptogenic therapy for epilepsy associated with vascular injury. Twit Text FOAVip Losartan prevents acquired epilepsy via TGF- signaling suppression ????Ann Neurol http://www.kidney.de/pget.php?&tw=1&pmid=24659129 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24659129 #FOAvip English Wikipedia <ref>{{Cite pmid|24659129}}</ref> Losartan prevents acquired epilepsy via TGF-? signaling suppression #MMPMID24659129 Bar-Klein G; Cacheaux LP; Kamintsky L; Prager O; Weissberg I; Schoknecht K; Cheng P; Kim SY; Wood L; Heinemann U; Kaufer D; Friedman A Ann Neurol 2014[Jun]; 75 (6): 864-75 PMID24659129show ga Objective: Acquired epilepsy is frequently associated with structural lesions following trauma, stroke and infections. While seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor ? (TGF-?) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-? signaling and tested the efficacy of blocking the TGF-? pathway in preventing epilepsy. Methods: We addressed the role of TGF-? signaling in epiletogenesis in two different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, magnetic resonance and direct optical imaging for blood-brain barrier (BBB) permeability and vascular reactivity. Long-term electrocorticographic (ECoG) recordings were acquired in freely behaving animals. Results: We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 (ALK5) pathway of TGF-? receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist (AT1), losartan, previously identified as a blocker of peripheral TGF-? signaling, effectively blocks albumin-induced TGF-? activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation: TGF-? signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, an FDA-approved drug, as an efficient anti-epileptogenic therapy for epilepsy associated with vascular injury. äLosartan prevents acquired epilepsy via TGF-? signaling suppression (epmc).pdf DeepDyve Pubget Overpricing