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