Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms

Elisa Laaksamo, Manasi Ramachandran, Juhana Frösen, Riikka Tulamo, Marc Baumann, Robert M. Friedlander, Robert Harbaugh, Juha Hernesniemi, Mika Niemelä, Madhavan L. Raghavan, Aki Laakso

Research output: Contribution to journalArticle

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Abstract

Background: Size and morphological features are associated with intracranial aneurysm (IA) rupture. The cellular mechanisms of IA development and rupture are poorly known. Objective: We studied the expression and phosphorylation of different intracellular signaling molecules in the IA wall compared with IA morphological features to understand better the cellular pathways involved in IA development and wall degeneration. Methods: Nine ruptured and 17 unruptured human IA samples were collected intraoperatively. The expression levels and phosphorylation state of 3 mitogen-activated protein kinases (c-Jun N-terminal kinase [JNK], p38, extracellular signal-regulated kinase [ERK]), Bcl-2 antagonist of cell death (Bad), mammalian target of rapamycin (mTOR), cyclic AMP response element binding protein (CREB), and Akt were determined by Western blotting. The localization of signaling proteins was determined by immunofluorescence. From 3-dimensional segmentation of computed tomography angiographic data, size and shape indexes were calculated. Results: We found a 5-fold difference in phospho-Bad levels between ruptured and unruptured IAs. Phospho-mTOR was downregulated 2.5-fold in ruptured IAs. Phospho-p54 JNK, phospho-p38, and phospho-Akt levels correlated positively with IA size. Phospho-CREB levels were significantly associated with nonsphericity and ellipticity indexes. Phospho-Akt and phospho-p38 correlated negatively with undulation index. Conclusion: The signaling pathway profile (apoptosis, cell proliferation, stress signaling) differs between ruptured and unruptured IAs and is associated with IA geometry. Our results increase the knowledge of IA development and wall degeneration.

Original languageEnglish (US)
Pages (from-to)1565-1572
Number of pages8
JournalNeurosurgery
Volume70
Issue number6
DOIs
StatePublished - Jun 1 2012

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Intracranial Aneurysm
Rupture
Cyclic AMP Response Element-Binding Protein
Sirolimus
Cell Death
Phosphorylation
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Fluorescent Antibody Technique
Phosphotransferases
Down-Regulation
Western Blotting
Tomography
Cell Proliferation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Laaksamo, E., Ramachandran, M., Frösen, J., Tulamo, R., Baumann, M., Friedlander, R. M., ... Laakso, A. (2012). Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms. Neurosurgery, 70(6), 1565-1572. https://doi.org/10.1227/NEU.0b013e31824c057e
Laaksamo, Elisa ; Ramachandran, Manasi ; Frösen, Juhana ; Tulamo, Riikka ; Baumann, Marc ; Friedlander, Robert M. ; Harbaugh, Robert ; Hernesniemi, Juha ; Niemelä, Mika ; Raghavan, Madhavan L. ; Laakso, Aki. / Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms. In: Neurosurgery. 2012 ; Vol. 70, No. 6. pp. 1565-1572.
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Laaksamo, E, Ramachandran, M, Frösen, J, Tulamo, R, Baumann, M, Friedlander, RM, Harbaugh, R, Hernesniemi, J, Niemelä, M, Raghavan, ML & Laakso, A 2012, 'Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms', Neurosurgery, vol. 70, no. 6, pp. 1565-1572. https://doi.org/10.1227/NEU.0b013e31824c057e

Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms. / Laaksamo, Elisa; Ramachandran, Manasi; Frösen, Juhana; Tulamo, Riikka; Baumann, Marc; Friedlander, Robert M.; Harbaugh, Robert; Hernesniemi, Juha; Niemelä, Mika; Raghavan, Madhavan L.; Laakso, Aki.

In: Neurosurgery, Vol. 70, No. 6, 01.06.2012, p. 1565-1572.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms

AU - Laaksamo, Elisa

AU - Ramachandran, Manasi

AU - Frösen, Juhana

AU - Tulamo, Riikka

AU - Baumann, Marc

AU - Friedlander, Robert M.

AU - Harbaugh, Robert

AU - Hernesniemi, Juha

AU - Niemelä, Mika

AU - Raghavan, Madhavan L.

AU - Laakso, Aki

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Background: Size and morphological features are associated with intracranial aneurysm (IA) rupture. The cellular mechanisms of IA development and rupture are poorly known. Objective: We studied the expression and phosphorylation of different intracellular signaling molecules in the IA wall compared with IA morphological features to understand better the cellular pathways involved in IA development and wall degeneration. Methods: Nine ruptured and 17 unruptured human IA samples were collected intraoperatively. The expression levels and phosphorylation state of 3 mitogen-activated protein kinases (c-Jun N-terminal kinase [JNK], p38, extracellular signal-regulated kinase [ERK]), Bcl-2 antagonist of cell death (Bad), mammalian target of rapamycin (mTOR), cyclic AMP response element binding protein (CREB), and Akt were determined by Western blotting. The localization of signaling proteins was determined by immunofluorescence. From 3-dimensional segmentation of computed tomography angiographic data, size and shape indexes were calculated. Results: We found a 5-fold difference in phospho-Bad levels between ruptured and unruptured IAs. Phospho-mTOR was downregulated 2.5-fold in ruptured IAs. Phospho-p54 JNK, phospho-p38, and phospho-Akt levels correlated positively with IA size. Phospho-CREB levels were significantly associated with nonsphericity and ellipticity indexes. Phospho-Akt and phospho-p38 correlated negatively with undulation index. Conclusion: The signaling pathway profile (apoptosis, cell proliferation, stress signaling) differs between ruptured and unruptured IAs and is associated with IA geometry. Our results increase the knowledge of IA development and wall degeneration.

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Laaksamo E, Ramachandran M, Frösen J, Tulamo R, Baumann M, Friedlander RM et al. Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms. Neurosurgery. 2012 Jun 1;70(6):1565-1572. https://doi.org/10.1227/NEU.0b013e31824c057e