MAPK Pathway
MAPKs are a type of threonine and serine protein kinase that has many functions in cell biology. MAPK pathways are initiated when TLR, TNF, and IL receptors, as well as receptor tyrosine kinases, are activated (RTK). The three major MAPK families in humans are extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and C-Jun N-terminal kinase (JNK) (Khey, Huard & Mahmoud, 2020). The majority of prior investigations used MAPK inhibitors or inhibitors of their upstream signaling molecules and demonstrated that MAPK inhibition prevented vasospasm (Suzuki, Hasegawa, Kanamaru & Zhang, 2011) conducted an experiment and concluded that.  (Maddahi, Povlsen & Edvinsson, 2012) found that IL-1, IL-6, MMP-9, and pERK1/2 protein expression levels in cerebral arteries increased with time, with an early peak at roughly 6 h and a late peak at 48 to 72 h post-SAH. The elevated expression of TNF in cerebral arteries began at 24 hours and continued until 96 hours. In addition, the animals developed sensorimotor and spontaneous behavioral abnormalities as a result of SAH. They went on to say that SAH causes early activation of the MEK-ERK1/2 pathway in cerebral artery walls, which is linked to proinflammatory cytokines and MMP-9 upregulation. U0126 (selective inhibitor) suppressed the MEK-ERK1/2(mitogen-activated protein kinase kinase-extracellular signal-regulated kinases 1/2) pathway 6 hours after SAH, reducing the activation of cytokines and MMP-9 in cerebral arteries and improving neurological outcome. In canine and rabbit models, blocking the p38 MAPK pathway was found to be efficient in lowering inflammatory cytokine production, including IL-1, IL-1, IL-8, and TNF-α. In addition, as compared to the control group, the scientists saw a decrease in vasospasm (Pan et al., 2013; Sasaki et al., 2004). By activating p38MAPK/MMP-9 and degrading ZO-1, TREM-1 may play a crucial role in the development of EBI following SAH. According to the authors, TREM-1 inhibition alleviated the severity of SAH-induced EBI, establishing a novel method for EBI treatment (Sun, Duan, Jing, Wang, Hou & Zhang, 2019).