NITRIC OXIDE PATHWAY
The enzyme nitric oxide synthase (NOS) catalyzes the interaction of
L-arginine with molecular oxygen to make L-citrulline and NO. There are
three forms of NOS that have been found so far: they constitutively
expressed, Neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible
NOS (iNOS) (Kleinert, Schwarz & Förstermann, 2003). NO, which is mostly
produced by iNOS, can be detrimental and pro-inflammatory in high doses.
However, the activities of nitric oxide are mostly influenced by the
cellular context, NO concentration (depending on distance from the NO
source), and the initial priming of immune cells, rather than the
enzymatic source (Guzik, Korbut & Adamek-Guzik, 2003). The brain’s NO
levels rise dramatically as a result of vertebral ischemia. This is
attributed to increased iNOS expression in reactive astrocytes and
neutrophils invading the ischemic brain 6–12 hours after the injury, as
well as increased eNOS and nNOS expression in the arteries and
parenchyma within an hour of the lesion (Iadecola, 1997; Kader,
Frazzini, Solomon & Trifiletti, 1993; Zhang et al., 1994). NO has
pro-inflammatory and cytotoxic effects at high doses, but it is known to
have anti-inflammatory and vasodilator characteristics under certain
situations (Coleman, 2001; Sharma, Al-Omran & Parvathy, 2007).
L-arginine treatment during the acute period improved symptoms in people
with mitochondrial myopathy, encephalopathy, and stroke-like episodes
(Koga et al., 2018). During an inhaled NO experiment, peripheral
vascular resistance was lowered in a child with traumatic brain injury,
despite no changes in middle cerebral artery blood flow, jugular bulb
oxygen saturations, or intracranial pressure (Vavilala, Roberts, Moore,
Newell & Lam, 2001). According to the researchers, the NO donor had no
effect on cerebral blood flow, cerebral perfusion pressure, or cerebral
steal in these people (Willmot, Ghadami, Whysall, Clarke, Wardlaw &
Bath, 2006). These disparities in results could explain NO toxicity or
insufficient NO exposure, which could be explained by differences in NO
concentration. More research is needed to determine the role of NO in
SAH, which is currently up for contention.