<p>Tanshinone IIA Promotes Axonal Regeneration in Rats with Focal Cerebral Ischemia Through the Inhibition of Nogo-A/NgR1/RhoA/ROCKII/MLC Signaling</p>

Abstract

The aim of this study was to evaluate the neuroprotective effect of tanshinone IIA (TSA) on focal cerebral ischemia in rats and to investigate whether it was associated with Nogo-A/NgR1/RhoA/Rho-associated protein kinase 2 (ROCKII)/myosin light chain (MLC) signaling. Methods: In this study, focal cerebral ischemia animal model was used. Neurological deficit scores and infarction volume were investigated to evaluate the neuroprotection of TSA. Hematoxylin-eosin staining, Nissl staining, and immunofluorescence staining were conducted to detect ischemic changes in brain tissue and changes in neurofilament protein 200 (NF200) and growth-associated protein-43 (GAP-43) expression, respectively. Western blotting and qRT-PCR analyses were used to detect the expression levels of NF200, GAP-43 and Nogo-A/NgR1/RhoA/ROCKII/MLC pathway-related signaling molecules. Results: TSA treatment can improve the survival rate of rats, reduce the neurological score and infarct volume, and reduce neuron damage. In addition, TSA also increased axon length and enhanced expression of NF200 and GAP-43. Importantly, TSA significantly attenuated the expression of Nogo-A, NgR1, RhoA, ROCKII, and p-MLC, and thus inhibiting the activation of this signaling pathway. Conclusion: TSA promoted axonal regeneration by inhibiting the Nogo-A/NgR1/RhoA/ ROCKII/MLC signaling pathway, thereby exerting neuroprotective effects in cerebral ischemia rats, which provided support for the clinical application of TSA in stroke treatment.

Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats

“…In addition to neurite growth and guidance, axonal regeneration could be constrained by neurite growth inhibitors. NogoA binding with NgR by initiating the downstream RhoA/ROCK-2 inhibits axonal regeneration and results in growth cone collapse ( Wang et al, 2020 ). Strategies stimulating axonal growth-promoting factors and suppressing growth-inhibiting signals may greatly improve axonal extension and neurological outcomes ( Lu et al, 2021 ).…”

Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS‐CoV‐2‐induced CNS complications

“…In various studies, the therapeutic potential of tanshinone IIA has been evaluated for the treatment of various CNS disorders. Some studies report that this compound has a significant protective effect against the spinal cord and cerebral ischemic injury by inhibiting the inflammatory responses, oxidative stress, and apoptosis (Gong, Zhang, et al, 2020; Huang et al, 2020; Li et al, 2020; Yao et al, 2017; Yin et al, 2012; Zhou, Bondy, et al, 2015), which can mediate by inhibiting the signaling pathways RAGE/NF‐κB, Nogo‐A/NgR1/RhoA/ROCKII/MLC, ERβ/IL‐10, and Notch (Chen et al, 2020; Ding et al, 2020; Li et al, 2020; Wang, Ni, et al, 2020). Has been reported that this compound also can ameliorate CNS autoimmunity by promoting the differentiation of regulatory T cells, which is important for the treatment of neuroinflammatory diseases (Gong, Liu, et al, 2020).…”

The Promising Role of a Zebrafish Model Employed in Neural Regeneration Following a Spinal Cord Injury

“…For example, Chondroitinase ABC degrades CSPGs, improving axonal regeneration in animal models [ 102 , 103 , 104 ]. Pharmaceutical agents targeting RhoA/ROCK and other signaling pathways have also shown potential [ 105 , 106 ]. Additionally, cell transplantation strategies offer promising avenues to modulate the glial scar environment [ 107 , 108 , 109 , 110 ].…”