Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin.

During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1-induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

Flow-related intracranial aneurysms associated with unfused arterial twigs relevant to different vascular anomalies: embryologic and hemodynamic considerations.

OBJECT: Cerebrovascular anomalies resulting from the persistence of unfused embryonic twig-like vessels are associated with intracranial aneurysms. All records of patients with ruptured intracranial aneurysms who were treated at our institution were retrospectively reviewed for the presence of aneurysm-associated, unfused, twig-like vessels in the middle cerebral artery (MCA). Such vessels were recorded as twig-like MCA (T-MCA) or twig-like networks of an anomalous collateral artery (T-NACA). Additionally, we sought to characterize vulnerable intracranial aneurysms associated with those vascular anomalies. METHODS: A total of 442 ruptured aneurysms were treated from June 2006 to November 2013; of these, 4 ruptured aneurysms exhibited the presence of ipsilateral, unfused, twig-like vessels. Computed tomography (CT) scans, three-dimensional CT angiography, and digital subtraction angiography (DSA) were performed immediately after the initial ictus. Data analysis included age, sex, Hunt and Hess grade (HHG), Fisher grade (FG), medical risk factors, angiographic architecture, operative methods and findings, radiologic outcomes, and Glasgow outcome scale (GOS). The average follow-up period was 26 months. RESULTS: Patient ages ranged from 26 to 49 years with a mean age of 41; there were two females and two males. All four patients showed FG IV, and three patients had unfavorable HHG (IV in 2 and V in one) at admission. An M1 segmental occlusion and an adjacent small aneurysmal pouch were detected with three-dimensional CT angiography in three patients. Hypertension was recorded in all patients. The initial DSA revealed T-MCA in one patient and T-NACA in three patients. Six aneurysms in all, including two unruptured aneurysms, were found; three ruptured aneurysms existed inside of the twigs. All but one patient required diverse treatment modalities, and four of the five aneurysms were completely occluded after treatment. The remaining aneurysm, treated only with gluing, disappeared during follow-up. In two of the three patients with T-NACA, atresia of the M1 segment was confirmed intraoperatively. The GOS during follow-up was recorded as favorable (good recovery) in two patients and unfavorable (severe disability and permanent vegetative state) in two patients. CONCLUSIONS: These unique vascular anomalies, T-MCA and T-NACA, which are caused by heterogeneous maldevelopment of the primitive cerebral vessels, are not benign because of their frequent association with flow-related aneurysms, which are vulnerable to rupture. Microsurgical or endovascular treatments for this type of flow-related aneurysm associated with twigs are mandatory to prevent fatal rebleeding, and more attention has to be given when physicians encounter steno-occlusive MCA lesions in patients with subarachnoid hemorrhage to detect any vulnerable aneurysms associated with twig-like vessels.

Persistent carotid-vertebrobasilar anastomoses: how and why differentiating them?

The persistent carotid-vertebrobasilar anastomoses (PCVBA) can be explained by an interruption of the vertebrobasilar system (VBS) embryogenesis. We present two very rare cases of persistent anastomoses: a hypoglossal artery and a type I proatlantal artery, insisting on the angiographic criteria allowing differentiation. After a brief review of the embryogenesis of the VBS, we describe the different types of persistent anastomoses (hypoglossal, type I and II proatlantal, trigeminal and otic arteries). We will insist on the potential risks, not well-known, but typical of each anastomosis. PCVBA usually are incidental findings but imaging follow-up may be required since aneurysms may develop.