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INNOSC Theranostics and
Pharmacological Sciences Novel pharmacologic therapies for SAH

(v) Immune cell infiltration: In some cases, peripheral (ix) Inflammatory response: SAH initiates an
immune cells may infiltrate the injured brain tissue, inflammatory cascade that affects perivascular
amplifying the immune response and potentially nerves. Inflammatory molecules, such as cytokines
contributing to secondary brain injury. and chemokines, activate or sensitize nerve fibers,
(vi) Perivascular innervation: Cerebral blood vessel thereby enhancing their vasoactive effects. This
contractions are concentration dependent and inflammation-induced neuronal sensitization may
occur when noradrenaline is administered in result in sustained vasoconstriction, contributing to
situ or in vitro. It seems that pial veins are more DCI.
noradrenaline sensitive than pial arterioles. (x) Altered neurotransmitter release: SAH disrupts
Specifically, α-adrenoceptor blockers can prevent the release and reuptake of neurotransmitters at
these contractile responses. According to thorough perivascular nerve terminals. This dysregulation
receptor characterizations, the brain vasculature can lead to sustained vasoconstriction, increased
of certain animals (like dogs and cats) has post- vascular resistance, and impaired autoregulation of
junctional α2-adrenoceptors, while adrenoceptors of cerebral blood flow.
the α1-subtype are found in the brain vessels of other The pathophysiology of complications is illustrated in
animals (such as rats, monkeys, and humans) . Figure 2.
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(vii) Vasoactive neurotransmitters: The cerebral
vasculature is densely innervated by sympathetic 2.7. Potential therapeutic targets
and parasympathetic nerve fibers, which Understanding the role of perivascular innervation in SAH
release various neurotransmitters, including pathophysiology provides potential targets for therapeutic
norepinephrine and acetylcholine, regulating interventions. Modulating the activity of perivascular
vascular tone. In SAH, the balance between these nerves or their neurotransmitters may help mitigate
neurotransmitters is disrupted due to the stress the vasoconstriction and inflammation associated with
response and inflammation, leading to alterations SAH, thereby improving cerebral perfusion and patient
in vascular tone and dysfunction that contribute to outcomes.
SAH. Cardiovascular and cardiac abnormalities are
believed to result from sympathetic nervous system In addition, vascular abnormalities often arise from
activation, which raises circulating catecholamine ruptured intracranial aneurysms or abnormal cerebral
levels. blood vessel dilations, leading to the sudden release
(viii) Sympathetic activation: SAH triggers a robust of blood into the subarachnoid space. Inflammatory
sympathetic nervous system response, resulting in responses ensue from the introduction of blood into the
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increased norepinephrine release. Norepinephrine subarachnoid space .
induces vasoconstriction of cerebral blood vessels, Hemodynamic disturbances lead to increased
potentially contributing to DCI in SAH patients. intracranial pressure (ICP) and reduced cerebral blood
This vasoconstriction can further reduce cerebral flow due to blood presence in the subarachnoid space,
blood flow and exacerbate brain injury. consequently initiating an inflammatory cascade with the

Figure 2. Pathophysiology of subarachnoid hemorrhage complications.

Volume 7 Issue 2 (2024) 5 doi: 10.36922/itps.2019