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Updated: Jul 30, 2026

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Increased macrophage M2/M1 ratio is associated with intracranial aneurysm rupture
Mária Hundža Stratilová1,2, Miroslav Koblížek2, Anna Štekláčová3
1Department of Neurosurgery, J. E. Purkyne University, Masaryk Hospital, Sociální péče 3316/12A, 400 13, Ústí Nad Labem, Czech Republic.
Purpose:
Intracranial aneurysm (IA) rupture results in one of the most severe forms of stroke, with severe neurological sequelae. Inflammation appears to drive aneurysm formation and progression with macrophages playing a key role in this process. However, less is known about their involvement in aneurysm rupture. This study is aimed at demonstrating how relationship between the M1 (pro-inflammatory) and M2 (reparative) macrophage subtypes affect an aneurysm's structure resulting in its rupture.
Methods:
Forty-one saccular aneurysm wall samples were collected during surgery including 13 ruptured and 28 unruptured aneurysm sacs. Structural changes were evaluated using histological staining. Macrophages in the aneurysm wall were quantified and defined as M1 and M2 using HLA-DR and CD163 antibodies. Aneurysm samples were divided into four groups according to the structural changes and the M2/1 ratio. Data were analyzed using the Mann-Whitney U test.
Results:
This study has demonstrated an association between the severity of structural changes of an aneurysm with inflammatory cell infiltration within its wall and subsequent aneurysm rupture. More severe morphological changes and a significantly higher number of inflammatory cells were observed in ruptured IAs (p < 0.001). There was a prevalence of M2 macrophage subtypes within the wall of ruptured aneurysms (p < 0.001). A subgroup of unruptured IAs with morphological and inflammatory changes similar to ruptured IAs was observed. The common feature of this subgroup was the presence of an intraluminal thrombus.
Conclusions:
The degree of inflammatory cell infiltration associated with a shift in macrophage phenotype towards M2 macrophages could play an important role in structural changes of the aneurysm wall leading to its rupture.
Insights
Inflammation and M2 macrophages in intracranial aneurysms are linked to rupture. A shift towards M2 macrophages may drive structural changes leading to aneurysm rupture.
Area of Science:
- Neurology
- Pathology
- Immunology
Background:
- Intracranial aneurysm (IA) rupture causes severe stroke.
- Inflammation drives IA formation and progression, with macrophages playing a key role.
- The role of macrophages in IA rupture is less understood.
Purpose of the Study:
- To investigate the relationship between M1 (pro-inflammatory) and M2 (reparative) macrophage subtypes and IA structural changes leading to rupture.
- To quantify macrophage subtypes in ruptured and unruptured IA walls.
Main Methods:
- Collected 41 saccular IA wall samples (13 ruptured, 28 unruptured).
- Assessed structural changes via histological staining.
- Quantified M1 (HLA-DR+) and M2 (CD163+) macrophages.
- Analyzed data using the Mann-Whitney U test.
Main Results:
- Ruptured IAs showed more severe structural changes and higher inflammatory cell infiltration (p < 0.001).
- M2 macrophage subtypes were prevalent in ruptured IA walls (p < 0.001).
- A subgroup of unruptured IAs with similar changes had intraluminal thrombi.
Conclusions:
- Increased inflammatory cell infiltration and a shift towards M2 macrophages are associated with IA structural changes and rupture.
- M2 macrophage polarization may be a key factor in IA wall weakening and rupture.

