Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations

Sure, Ulrich; Butz, Nick; Schlegel, Jürgen; Siegel, Adrian M.; Wakat, Jörg P.; Mennel, H. D.; Bien, Siegfried; Bertalanffy, Helmut

doi:10.3171/jns.2001.94.6.0972

Cited by 173 publications

(110 citation statements)

References 47 publications

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“…PCNA immunostaining was positive in 36 of 42 CAs (86%), 13) and 11 of 13 CAs (85%) and 20 of 25 AVMs (80%). 23) In our study, rates of positive PCNA immunostaining were lower at 12 of 27 CAs and 10 of 20 AVMs, possibly due to technical differences such as resection and fixation proce-…”

Section: Discussionmentioning

confidence: 78%

“…3,9,15,18,20) The underlying developmental and pathogenetic mechanisms of these malformations are not completely understood, but may involve the proliferative and angiogenic capacities of the endothelium. 7,13,21,23) Nestin is one of the intermediate filaments abundantly produced in the developing central nervous system and somites in the embryonic stage of rodents, and is used as a marker of neuroepithelial stem cells. 11,28) Expression of nestin is high in the cerebrum of the developing mouse embryo, peaking at embryonic day 15, and declines with further growth.…”

Section: Introductionmentioning

confidence: 99%

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Nestin Expression in Vascular Malformations: A Novel Marker for Proliferative Endothelium

Shimizu

Sugawara

Tosaka

et al. 2006

Neurol. Med. Chir.(Tokyo)

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Cavernous angiomas (CAs) and arteriovenous malformations (AVMs) sometimes show growth or de novo appearance. Proliferative capacity of the endothelium is evident in such malformations. Intermediate filament nestin is a newly identified marker for proliferative endothelium, which was originally detected in the neuroepithelial stem cells of the embryonal central nervous system. Immunohistochemical analysis of nestin was evaluated as a marker for proliferative capacity of endothelial cells by comparison with proliferating cell nuclear antigen (PCNA). Sixteen of 27 CAs and 13 of 20 AVMs were positive for nestin. Likewise, 12 of 27 CAs and 10 of 20 AVMs were positive for PCNA. Nestin staining was stronger in the typical malformative vessels of CAs than in AVMs, in both the endothelial cells and the interstitial cells. Newly formed endothelial cells expressed nestin strongly in the reactive tissues including organizing or encapsulated hematomas. These results suggest that neovascularization occurs in the process of repeated bleeding and remodeling of hematomas.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Nestin Expression in Vascular Malformations: A Novel Marker for Proliferative Endothelium

Shimizu

Sugawara

Tosaka

et al. 2006

Neurol. Med. Chir.(Tokyo)

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“…Kavernomların literatürde kavernöz anjiom, kavernöz malformasyon, anjografik olarak okkült vasküler malformasyon şeklinde geniş bir aralık-ta isimlendirildiği görülmektedir (1). Literatürde kavernom, kapiller telenjiyektazi ve GVA'nın aynı hastalığın bir spektrumu olduğunu belirten çalışmalar bulunduğu gibi kavernomların GVA'dan geliştiğini belirten yayınlarda bulunmaktadır (1,(6)(7)(8). GVA'nın bir dalında oklüzyon gelişmesi, radyoterapiye maruz kalması, KRIT1 ya da diğer bilinen mutasyonlar gibi genetik faktörler sonucu GVA'dan kavernom gelişebildi-ği belirtilmektedir (6).…”

Section: Discussionunclassified

Serebral Kavernomların Manyetik Rezonans Görüntüleme Bulguları

Gökçe¹,

Beyhan²,

Acu³

et al. 2016

Kocatepe Tıp Dergisi

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Amaç: Serebral kavernomlar, arasında normal beyin parankimi olmayan anormal genişlemiş kapiller kavitelerle karakterize vasküler malformasyonlardır. Bu çalışmada serebral kavernomların manyetik rezonans görüntüleme (MRG) bulguları sunulmaktadır.Gereç ve Yöntem: Çalışmaya çeşitli nörolojik şikayetleri nedeniyle beyin MRG tetkiki uygulanan ve tetkiklerinde kavernom saptanan, 19'u kadın, 17'si erkek toplam 36 hasta dahil edildi. MRG'de kavernomların tipleri, yerleşim alanları, volümleri, T2A serilerde hemosiderin halkalarının varlığı ve şekli, eşlik eden gelişimsel venöz anomali (GVA) varlığı, kontrastlı serilerde kontrastlanma paternleri araştırıldı. Kavernomların volümleri ile kontrastlanma arasındaki ilişki araştırıldı.Bulgular: Otuzaltı kavernomun 17'si kortikal-subkortikal, 11'i derin, 5'i subkortikal-santral beyaz cevher, üçü santral beyaz cevherde yerleşimliydi. Kavernomların hacimleri 0,02-6,50 ml (ortanca 0,45 ml) arasında değişmekteydi. Kavernomların 19'unda kesintili, 15'inde kesintisiz hemosiderin halkası varken ikisinde saptanamadı. Kavernomların 23'ü keskin, 11'nispeten düzgün konturlu iken ikisi belirsiz sınırlı olup bunların şekil itibariyle 24'ü lobule, 11'i yuvarlak, biri şekilsizdi. Zabramski sınıflamasına göre kavernomların 22'si Tip 2, 13'ü Tip 1 ve biri de Tip 3'tü. Kavernomların 14'ünde kontrastlanma saptanmazken, 7'sinde progresif, üçünde fokal-punktat, üçünde periferal, birinde ise difüz kontrastlanma görüldü. Kavernom volümleri ile kontrastlanma arasında istatistiki olarak anlamlı ilişki saptanmadı (p=0,382). Hastaların 18'inde kavernoma GVA eşlik etmekteydi.Sonuç: Kavernomlar sıklıkla GVA'nın eşlik ettiği, içerisindeki kanama ürünlerinin miktarı ve evresine göre değişken MR görünüm özellikleri sergileyen, volümden bağımsız farklı kontrastlanma paternleri içeren vasküler orjinli lezyonlardır.

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“…10) In fact, angiogenic growth factors, such as vascular endothelial growth factor (VEGF), may be involved in the development of cavernous malformation. 13,14) In the present case, we examined the expression of extracellular matrix proteins including MMP-2 and -9, and the endogenous inhibitor TIMP-2, and found increased endothelial expression of MMP-2 and -9, and TIMP-2 only in the cavernous malformation.…”

Section: Discussionmentioning

confidence: 99%

Association of Cavernous Malformation Within Vestibular Schwannoma: Immunohistochemical Analysis of Matrix Metalloproteinase-2 and -9 -Case Report-

Sakata

Fujimura

Watanabe

et al. 2007

Neurol. Med. Chir.(Tokyo)

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A 65-year-old man presented with a rare case of cavernous malformation with hemorrhage located within vestibular schwannoma. He had suffered hearing impairment for 20 years, and was admitted to our hospital with vertigo and ataxic gait. Neurological examination revealed hearing loss, facial nerve paresis, and left cerebellar ataxia. Magnetic resonance imaging demonstrated a left vestibular schwannoma 35 mm in diameter, as well as a heterogeneous area associated with hypointense rim within the tumor, indicating intratumoral hemorrhage. Subtotal removal of the tumor together with the fibrously encapsulated hematoma was performed through a left retrosigmoid craniotomy. Histological examination of the surgical specimen revealed cavernous malformation within vestibular schwannoma. Immunohistochemistry for matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitors of metalloproteinase-2 showed strong expression in the endothelial cells of the cavernous malformation, but not in the interstitial structures. His symptoms significantly improved after surgery and he underwent gamma-knife therapy for the residual tumor. Cavernous malformations may show dynamic characteristics such as repeated hemorrhage and de novo formation. MMP-2 and -9, which are implicated in angiogenesis and hemorrhage, may be upregulated in such tumors.

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Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations

Cited by 173 publications

References 47 publications

Nestin Expression in Vascular Malformations: A Novel Marker for Proliferative Endothelium

Nestin Expression in Vascular Malformations: A Novel Marker for Proliferative Endothelium

Serebral Kavernomların Manyetik Rezonans Görüntüleme Bulguları

Association of Cavernous Malformation Within Vestibular Schwannoma: Immunohistochemical Analysis of Matrix Metalloproteinase-2 and -9 -Case Report-

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