Page 10 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Novel pharmacologic therapies for SAH

mediated by cytokines and immune cells, can 2.5. Seizure burden associated with clinical outcome
exacerbate tissue damage. A study conducted by De Marchis et al. focused on the
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(iii) Vasoconstriction: Hemoglobin and its degradation clinical and functional outcomes in SAH patients with
products, such as bilirubin, can induce vasoconstriction respect to seizures. The study included every patient
and impair cerebral blood flow regulation. This can with spontaneous SAH consecutively admitted and
result in complications like cerebral vasospasm, continuously monitored with an electroencephalogram in
which is associated with poor outcomes in SAH the neurological intensive care unit at Columbia University
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patients. Towner et al. discuss the use of mechanical Medical Center. The number of hours with seizures
ventilation in aneurysmal SAH, potentially touching recorded on continuous EEG (cEEG) was used to quantify
upon the role of vasoconstriction in the context of the seizure load. Cognitive results were evaluated using the
ventilatory support. Telephone Interview for Cognitive Status. In 12% of SAH

2.3. Blood in subarachnoid space patients undergoing cEEG monitoring, whose primary
purpose was to screen for cerebral ischemia, seizures
Voldby conducted a literature review highlighting the occurred. Since none of the seizures were convulsive, cEEG
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relationship between SAH and cerebral vasospasm. would not have detected them. Three months after SAH, a
They emphasize that the initial insult, characterized by significant correlation was found between the likelihood
the presence of blood in the subarachnoid space due to of a poor functional outcome and the occurrence of
aneurysmal rupture or other causes, triggers a cascade both non-convulsive seizures (NCSZ) and seizure load.
of events leading to vasospasm. The presence of blood However, the occurrence of NCSZ alone was not related
components, particularly hemoglobin breakdown to cognitive results at 3 months; only the seizure load
products, contributes to inflammation and dysfunction of showed a correlation. The more nuanced relationship
cerebral blood vessels, ultimately resulting in vasospasm – between seizure load and cognitive outcome implies that
a hallmark complication of SAH. seizure prophylactic measures should not be separated
Voldby provides insights into the pathophysiology of from therapeutic approaches aimed at reducing seizure
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SAH based on both experimental and clinical data. The burden .
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presence of blood in the subarachnoid space is identified
as a primary event. This blood irritates the meninges and 2.6. Inflammation and immune response
surrounding brain tissues, triggering an inflammatory SAH triggers an inflammatory response involving immune
response. In addition, breakdown products of hemoglobin, cells and the release of pro-inflammatory cytokines,
such as bilirubin, exert toxic effects on brain tissue, potentially contributing to secondary brain injury . The
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exacerbating the damage caused by SAH. inflammatory and immune responses in SAH include
several key processes:
Collectively, these references emphasize the pivotal
role of blood within the subarachnoid space in the (i) Blood–brain barrier (BBB) disruption: The presence
of blood in the subarachnoid space can lead to the
pathophysiology of SAH. This presence triggers a cascade
of events, including inflammation and cerebral vasospasm, disruption of the blood–brain barrier, allowing
which contribute to the clinical manifestations and immune cells and inflammatory molecules to enter
complications associated with this condition . the brain tissue.
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(ii) Immune cell activation: Resident immune cells
2.4. Vasospasm and reduced cerebral blood flow in the brain, such as microglia and macrophages,
become activated in response to blood products.
As mentioned earlier, the study conducted by Voldby They phagocytize red blood cells and release
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contributed experimental and clinical data on the pro-inflammatory cytokines, contributing to
pathophysiology of SAH. While not directly addressing neuroinflammation.
vasospasm and reduced blood flow, these data likely enhance (iii) Cytokine release: Inflammatory cytokines,
a broader understanding of the influence exerted by these such as tumor necrosis factor-alpha (TNF-α)
factors on the development and progression of SAH. and interleukin-1 beta (IL-1β), are released in

In a related context, Hayman et al. discussed the response to SAH. These cytokines can exacerbate
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pathophysiology of acute intracerebral and SAH. They inflammation and neuronal injury.
emphasized the impact of reduced blood flow on brain (iv) Oxidative stress: The breakdown of hemoglobin from
tissue, particularly in the context of SAH. Insufficient the lysed red blood cells leads to the release of heme,
blood supply can result in ischemia, contributing to the generating ROS and causing oxidative stress. This
development of SAH-related complications. oxidative stress further contributes to tissue damage.

Volume 7 Issue 2 (2024) 4 doi: 10.36922/itps.2019