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).