The effects of fasudil on the permeability of the rat blood–brain barrier and blood–spinal cord barrier following experimental autoimmune encephalomyelitis

The Therapeutic Potential of Rho Kinase Inhibitor Fasudil Derivative FaD-1 in Experimental Autoimmune Encephalomyelitis

“…Some observations in cultured neurons have discovered that the activation of Rho/ROCK caused the growth cone to collapse by affecting the actin skeleton system (Hall 1998). A series of studies have demonstrated that the expression and/or activity of ROCK were increased in different EAE models (Sun et al 2006;Yu et al 2010;Huang et al 2011;Hou et al 2012;Liu et al 2013). In this study, we demonstrate that FaD-1, as a ROCK inhibitor fasudil derivative, can inhibit ROCK II in spinal cord of EAE.…”

“…A series of studies have demonstrated that the expression and/or activity of ROCK were increased in different EAE models (Sun et al 2006;Yu et al 2010;Huang et al 2011;Hou et al 2012;Liu et al 2013). Previous investigations from our group and other labs have indicated that ROCK inhibitor fasudil ameliorated clinical severity of EAE at different models and different stages (Sun et al 2006;Yu et al 2010;Huang et al 2011;Liu et al 2013), accompanied by the improvement of demyelination and the inhibition of neuroinflammation (Sun et al 2006;Yu et al 2010;Hou et al 2012;Liu et al 2013).…”

“…Previous investigations from our group and other labs have indicated that ROCK inhibitor fasudil ameliorated clinical severity of EAE at different models and different stages (Sun et al 2006;Yu et al 2010;Huang et al 2011;Liu et al 2013), accompanied by the improvement of demyelination and the inhibition of neuroinflammation (Sun et al 2006;Yu et al 2010;Hou et al 2012;Liu et al 2013). The mechanism underlying the therapeutic potential of fasudil in EAE models include: (1) the downregulation of Th17 and Th1 T cells (Sun et al 2006;Yu et al 2010), (2) the protection of BBB and blood-spinal cord barrier (BSCB) integrity (Huang et al 2011), (3) the inhibition of TLR-4 and p-NF-kB/p65 inflammatory axis (Hou et al 2012), and (4) the shift from M1 to M2 macrophages (Liu et al 2013).…”

“…Some observations in cultured neurons have shown that the activation of Rho/ROCK caused the growth cone to collapse by affecting the actin skeleton system (Hall 1998). The inhibition of ROCK resulted in accelerated regeneration and enhanced functional recovery, and has also proved to be efficacious in animal models of stroke ), MS (Sun et al 2006;Yu et al 2010;Huang et al 2011;Hou et al 2012;Liu et al 2013), ALS (Takata et al 2013), Alzheimer's disease (Song et al 2013), and Parkinson's disease (Tönges et al 2012;Rodriguez-Perez et al 2013). Therefore, ROCK has been considered as a promising drug target for preventing neurodegeneration and stimulating neuroregeneration in several neurological diseases (Mueller et al 2005).…”

Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis

“…These inhibitors bind their receptor complex, including NgR1, the p75 neurotrophin receptor (p75NTR), and LINGO-1 [8], and downstream signaling leads to failure of remyelination and arrest of neurite/axon growth [9]. An important downstream pathway of these myelin-associated inhibitors (MAIs) is Rho molecules, especially RhoA, and their kinases (Rho kinases (ROCKs)), whose activities are considerably increased in several neurological disorders such as stroke, MS, Alzheimer's disease (AD), and Parkinson's disease (PD) [10,11], while the blockade of Rho/ROCK is thought to inhibit inflammation, to reduce infarct size [12], and to suppress EAE [13][14][15]. On the other hand, adenosine 3′,5′-cyclic monophosphate (cAMP) plays an important role in neuronal survival and modulation of growth cone and enhancement of neurite outgrowth [16].…”