Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage

Cecil O. Borel, Andy McKee, Augusto Parra, Michael M. Haglund, Amy Solan, Vikas Prabhakar, Huaxin Sheng, David S. Warner, Laura Niklason

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Background and Purpose - During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro. Methods - CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-Β1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies. Results - PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs. Conclusions - Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalStroke
Volume34
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Intracranial Vasospasm
Subarachnoid Hemorrhage
Blood Vessels
Cell Proliferation
Platelet-Derived Growth Factor
Cerebrospinal Fluid
Thrombosis
Mitogens
Arteries
Cerebral Arteries
Transforming Growth Factors
vascular factor
Neutralizing Antibodies
Vascular Endothelial Growth Factor A
Smooth Muscle
Fibroblasts
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Hemorrhage

Keywords

  • Cerebral arteries
  • Cerebral vasospasm
  • Growth factors
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Borel, C. O., McKee, A., Parra, A., Haglund, M. M., Solan, A., Prabhakar, V., ... Niklason, L. (2003). Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage. Stroke, 34(2), 427-432. https://doi.org/10.1161/01.STR.0000053848.06436.AB

Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage. / Borel, Cecil O.; McKee, Andy; Parra, Augusto; Haglund, Michael M.; Solan, Amy; Prabhakar, Vikas; Sheng, Huaxin; Warner, David S.; Niklason, Laura.

In: Stroke, Vol. 34, No. 2, 01.02.2003, p. 427-432.

Research output: Contribution to journalArticle

Borel, CO, McKee, A, Parra, A, Haglund, MM, Solan, A, Prabhakar, V, Sheng, H, Warner, DS & Niklason, L 2003, 'Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage', Stroke, vol. 34, no. 2, pp. 427-432. https://doi.org/10.1161/01.STR.0000053848.06436.AB
Borel, Cecil O. ; McKee, Andy ; Parra, Augusto ; Haglund, Michael M. ; Solan, Amy ; Prabhakar, Vikas ; Sheng, Huaxin ; Warner, David S. ; Niklason, Laura. / Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage. In: Stroke. 2003 ; Vol. 34, No. 2. pp. 427-432.
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AU - Borel, Cecil O.

AU - McKee, Andy

AU - Parra, Augusto

AU - Haglund, Michael M.

AU - Solan, Amy

AU - Prabhakar, Vikas

AU - Sheng, Huaxin

AU - Warner, David S.

AU - Niklason, Laura

PY - 2003/2/1

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N2 - Background and Purpose - During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro. Methods - CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-Β1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies. Results - PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs. Conclusions - Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.

AB - Background and Purpose - During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro. Methods - CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-Β1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies. Results - PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs. Conclusions - Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.

KW - Cerebral arteries

KW - Cerebral vasospasm

KW - Growth factors

KW - Subarachnoid hemorrhage

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