Page 183 - Read Online

Koseki et al. Inflammatory cells in intracranial aneurysm

INTRODUCTION medical IA treatment should be established for patients
without surgical indications, or as an alternative to
Despite the existence of intensive treatments and surgical procedures. Currently, statin is considered to
modern technical advancements in medical care, be a candidate therapeutic drug for IAs as our previous
subarachnoid hemorrhage caused by the rupture of case-control study demonstrated that statin usage
an intracranial aneurysm (IA) has a poor prognosis reduced the incidence of subarachnoid hemorrhage
with a mortality rate of up to 50%. In addition, due to the rupture of IAs. In addition, a prospective
[7]
[1]
subarachnoid hemorrhage can cause sudden death, randomized trial examining the inhibitory effect of
even in the productive population, making this disease statins on the progression and rupture of human IAs,
socially important. Given such a devastating outcome known as the Small Unruptured Aneurysm Verification
and difficulty in treatment once the subarachnoid Prevention Effect against Growth of cerebral Aneurysm
hemorrhage develops, rupture-preventing treatment Study Using Statin study (Japan), is in progress.
of IAs is essential. Currently, many IAs are incidentally However, the mechanisms underlying the pathogenesis
found before rupture through a medical checkup of the of IAs need to be further examined in order to develop
brain, particularly in developed countries. Indeed, in a effective and safe medical treatments. Thus, knowledge
Japanese cohort, the majority of unruptured IAs were regarding the cell types regulating the pathogenesis
found incidentally. The detection of unruptured IAs of IAs is essential to the identification of diagnostic
[2]
enables prophylactic interventions for the prevention or therapeutic targets. Although the histopathological
of rupture and the subsequent onset of subarachnoid examination of human IAs demonstrated the presence
hemorrhage. Currently, IAs with a high probability of of hyaline deposits, sub-intimal fibrin deposition, and
rupture are holistically selected using morphological laminar thrombosis in lesions, particularly in ruptured
aspects such as size and shape, anatomical aspects IAs, [4,8,9] thereby implicating endothelial dysfunction as
such as location, and other confounding factors which, a potential target for medical therapy, we focus on the
according to some guidelines and previous cohort inflammatory infiltrates found in IA walls in this short
studies, increase the likelihood of rupture, such as a review given previous findings that the inflammatory
previous or family history of subarachnoid hemorrhage, response is crucial in the pathogenesis of IAs. [10-13]
race (Japanese or Finnish), current smoking status,
or the presence of hypertension. IAs with a high risk INFLAMMATORY CELLS IN IA LESIONS
for rupture are surgically treated using microsurgical
or endovascular procedures. [3-5] In order to predict Histopathological analysis of surgically dissected
the risk of IA rupture more objectively and accurately, or autopsy-harvested IA specimens has revealed
a scoring system has been established based on a the presence of inflammatory cells in IA lesions.
meta-analysis of 6 prospective cohort studies on the Kataoka et al. demonstrated an increased presence
[9]
annual rupture risk of IAs. [3,6] However, the lack of a of inflammatory infiltrating immune cells in ruptured
diagnostic method to qualitatively estimate the rupture human IAs compared to that in unruptured IAs
risk for each IA is currently a major concern in IA with a positive correlation between inflammatory
treatment. The natural consequence is that IAs with a infiltrates and degenerative changes in the arterial
lower probability of rupture are sometimes surgically walls, suggesting a role for inflammatory cells in the
treated with a considerable risk for complications, or rupture of IAs. Inflammatory cells found in human
lesions on the verge of rupture are simply observed, IA lesions include macrophages, [14-16] neutrophils,
[17]
resulting in a devastating outcome. Therefore, a novel T lymphocytes [14,15] and mast cells. [16,18,19] Among
qualitative diagnostic method should be established these types of inflammatory cells, the contribution
in order to reduce inappropriate decisions regarding of macrophages, neutrophils, and mast cells to
surgical intervention. the pathogenesis of IAs has been supported by
experimental studies using animal IA models. Below,
Another important concern regarding current IA we review the evidence for each cell type.
treatment for rupture prevention is the lack of medical
treatment (expect for medical care targeting risk T cells
factors such as hypertension) for patients with IAs T cells are a major cell type participating in acquired
ill-suited for surgery, including patients with small immunity. T cells are differentiated in the thymus from
IAs or elderly patients with significant comorbidity. their precursors mainly into CD4-positive and CD8-
[6]
Considering the poor outcome associated with positive T cells. These differentiated T cell subsets are
subarachnoid hemorrhage after onset, the intrinsic risk then distributed throughout the body and are further
of complications related to surgical manipulations, and differentiated into effective subtypes according to the
the nature of unruptured IAs as asymptomatic lesions, microenvironment in situ, including CD8-positive T
174 Neuroimmunology and Neuroinflammation ¦ Volume 3 ¦ August 31, 2016