Skip to main content
Log in

Expression of vascular endothelial growth factor in dura mater of patients with moyamoya disease

  • Original Article
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Vascular endothelial growth factor (VEGF) has been found to be involved in vasculogenesis in different intracranial lesions. We investigated meningeal cellularity and VEGF expression in dura mater of patients with and without moyamoya disease. Nine dural specimens from nine cerebral hemispheres of seven patients with moyamoya disease and four control dural specimens from four non-moyamoya patients were collected during surgery and investigated. Dural specimens were immunohistochemically stained with VEGF antibody, and then meningeal cellularity and VEGF expression in dural tissue were analyzed. The mean ± standard error (SE) of total number of meningeal cells (meningeal cellularity) in dural tissue was 21.5 ± 3.0 in the moyamoya disease patients, whereas it was 2.7 ± 0.7 in control patients. The mean ± SE of VEGF expression was 51.1 ± 4.9% in the moyamoya disease patients, whereas it was 13.8 ± 5.9% in control patients. The meningeal cellularity and VEGF expression were statistically significantly higher in the moyamoya group in comparison to control group (p < 0.0001). Meningeal cellularity and VEGF expression are significantly increased in dura mater of the patients with moyamoya disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Cao Y, Hong A, Schulten H, Post MJ (2005) Update on therapeutic neovascularization. Cardiovasc Res 65:639–648

    Article  PubMed  CAS  Google Scholar 

  2. Dauser RC, Tuite GF, McCluggage CW (1997) Dural inversion procedure for moyamoya disease. Technical note. J Neurosurg 86:719–723

    PubMed  CAS  Google Scholar 

  3. Endo M, Kawano N, Miyaska Y, Yada K (1989) Cranial burr hole for revascularization in moyamoya disease. J Neurosurg 71:180–185

    PubMed  CAS  Google Scholar 

  4. Hoshi H, Ohnishi T, Jinnouchi S, Futami S, Nagamachi S, Kodama T, Watanabe K, Ueda T, Wakisaka S (1994) Cerebral blood flow study in patients with Moyamoya disease evaluated by IMP SPECT. J Nucl Med 35:44–50

    PubMed  CAS  Google Scholar 

  5. Hoshimaru M, Takahashi JA, Kikuchi H, Nagata I, Hatanaka M (1991) Possible roles of basic fibroblast growth factor in the pathogenesis of Moyamoya disease: an immunohistochemical study. J Neurosurg 75:267–270

    PubMed  CAS  Google Scholar 

  6. Jin KL, Mao XO, Nagayama T, Goldsmith PC, Greenberg DA (2000) Induction of vascular endothelial growth factor and hypoxia-inducible factor-1alfa by global ischemia in rat brain. Neuroscience 99:577–585

    Article  PubMed  CAS  Google Scholar 

  7. Kashiwagi S, Kato S, Yasuhara S, Wakuta Y, Yamashita T, Ito H (1996) Use of a split dura for revascularization of ischemic hemispheres in Moyamoya disease. J Neurosurg 85:380–383

    Article  PubMed  CAS  Google Scholar 

  8. Kuwabara Y, Ichiya Y, Otsuka M, Tahara T, Gunasekera R, Hasuo K, Masuda K, Matsushima T, Fukui M (1990) Cerebral hemodynamic change in the child and the adult with Moyamoya disease. Stroke 21:272–277

    PubMed  CAS  Google Scholar 

  9. Matsushima T, Fujiwara S, Nagata S, Fujii K, Fukui M, Kitamura K, Hasuo K (1989) Surgical treatment for paediatric patients with moyamoya disease by indirect revascularization procedures (EDAS, EMS, EMAS). Acta Neurochir (Wien) 98:135–140

    Article  CAS  Google Scholar 

  10. Matsushima T, Inoue T, Suzuki SO, Fujii K, Fukui M, Hasuo K (1992) Surgical treatment of moyamoya disease in pediatric patients—comparison between the results of indirect and direct revascularization procedures. Neurosurgery 31:401–405

    Article  PubMed  CAS  Google Scholar 

  11. Matsushima Y (1998) Indirect anastomoses for Moyamoya disease. No Shinkei Geka 26:769–786 (Jpn)

    PubMed  CAS  Google Scholar 

  12. Nanba R, Kuroda S, Ishikawa T, Houkin K, Iwasaki Y (2004) Increased expression of hepatocyte growth factor in cerebrospinal fluid and intracranial artery in moyamoya disease. Stroke 35:2837–2842

    Article  PubMed  CAS  Google Scholar 

  13. Sakamoto S, Ohba S, Shibukawa M, Kiura Y, Arita K, Kurisu K (2006) CT perfusion imaging for childhood moyamoya disease before and after surgical revascularization. Acta Neurochir (Wien) 148:77–81

    Article  CAS  Google Scholar 

  14. Suzuki J, Takaku A (1969) Cerebrovascular “Moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 20:288–299

    PubMed  CAS  Google Scholar 

  15. Takekawa Y, Umezawa T, Ueno Y, Sawada T, Kobayashi M (2004) Pathological and immunohistochemical findings of an autopsy case of adult moyamoya disease. Neuropathology 24:236–242

    Article  PubMed  Google Scholar 

  16. Touho H, Karasawa J, Ohnishi H (1996) Preoperative and postoperative evaluation of cerebral perfusion and vasodilatory capacity with 99mTc-HMPAO SPECT and acetazolamide in childhood Moyamoya disease. Stroke 27:282–289

    PubMed  CAS  Google Scholar 

  17. Yamada I, Matsushima Y, Suzuki S (1992) Childhood moyamoya disease before and after encephalo-duro-arterio-synangiosis: an angiographic study. Neuroradiology 34:318–322

    Article  PubMed  CAS  Google Scholar 

  18. Yamasaki F, Yoshioka H, Hama S, Sugiyama K, Arita K, Kurisu K (2000) Recurrence of meningiomas. Cancer 89:1102–1110

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shigeyuki Sakamoto.

Additional information

Comments

Kiyohiro Houkin, Sapporo, Japan

The pathogenesis of moyamoya disease is still unknown. There have been various approaches attempted to open this hard gate. Those included the microsattelite analysis of gene using the familial pedigree cases of moyamoya disease, gene expression analysis of the tissue sample from the patient, and investigation of the substance specific to this disease. However, so far, the survey of the gene closely related to moyamoya disease has not reached to confirmation of specific gene. In addition, there is no particular pattern of gene expression reported using the sample of moyamoya disease.

Among these reports, there are some cytokines, FGF, VEGF, HGF, that are suggested to be related to moyamoya disease. In this paper, the VEGF expression is significantly increased in the dura mater of the patients with moyamoya disease. In addition, the cellularity of the dural tissue was significantly high in moyamoya disease.

These facts are quite remarkable because those suggested the pathological process of moyamoya disease reaches not only to the intracerebral vascularity but also meningeal (extracerebral tissue). However, as it is true for other paper similar to this paper, the increase in VEGF expression and increased cellularity of dural tissue is not always considered the primary mechanism of this disease. On the other hand, it is conceivable that these increases may be a result of the specific ischemia of the moyamoya disease.

This paper has added novel fact to the hints to consider the pathogenesis of moyamoya disease. However, it is true that it is very far from the core mechanism of this unusual disease that the primary lesion is the centripetal narrowing of the anterior part of the Willis ring.

Michael T. Lawton, San Francisco, CA, USA

Sakamoto and colleagues compared dural tissue specimens in patients with and without moyamoya disease and demonstrated increased meningeal cellularity, greater numbers of VEGF-positive cells, and higher VEGF labeling indices in moyamoya patients as compared to aneurysm patients. In addition, STA–MCA bypass with encephalo-myo-synangiosis was more effective than encephalo-duro-synangiosis, with greater revascularization responses observed on follow-up angiography. Involvement of VEGF in the brain’s response to moyamoya disease is not surprising—increased VEGF expression has been demonstrated in many conditions of altered cerebral blood flow. VEGF expression in the dura is an intriguing finding, but one that is difficult to interpret without similar measures of VEGF expression in the brain, where there is active tissue ischemia. If brain specimens could have been collected simultaneously, VEGF expression in brain would probably have been higher than in dura. The authors speculate that a natural anatomical barrier in the dura limits the response of the middle meningeal artery to brain ischemia, and accounts for angiographic results with direct bypass that are superior to indirect bypass. I am not sure about the existence of this anatomical barrier, but nonetheless favor direct bypass in my moyamoya patients.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakamoto, S., Kiura, Y., Yamasaki, F. et al. Expression of vascular endothelial growth factor in dura mater of patients with moyamoya disease. Neurosurg Rev 31, 77–81 (2008). https://doi.org/10.1007/s10143-007-0102-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-007-0102-8

Keywords

Navigation