Impaired vascular remodeling after endothelial progenitor cell transplantation in MMP9-deficient mice suffering cortical cerebral ischemia.

Endothelial progenitor cells (EPCs) are being investigated for advanced therapies, and matrix metalloproteinase 9 (MMP9) has an important role in stroke recovery. Our aim was to determine whether tissue MMP9 influences the EPC-induced angiogenesis after ischemia. Wild-type (WT) and MMP9-deficient mice (MMP9/KO) were subjected to cerebral ischemia and treated with vehicle or outgrowth EPCs. After 3 weeks, we observed an increase in the peri-infarct vessel density in WT animals but not in MMP9/KO mice; no differences were found in the vehicle-treated groups. Our data suggest that tissue MMP9 has a crucial role in EPC-induced vascular remodeling after stroke.

Brain vein disorders in newborn infants.

The brain veins of infants are in a complex phase of remodelling in the perinatal period. Magnetic resonance venography and susceptibility-weighted imaging, together with high-resolution Doppler ultrasound, have provided new tools to aid study of venous developmental anatomy and disease. This review aims to provide a comprehensive background of vein development and perinatal venous lesions in preterm and term-born infants, and to encourage further research in both the fetus and the newborn infant, with the aim of preventing or mitigating parenchymal injury related to diseases involving veins.

The association between cerebral developmental venous anomaly and concomitant cavernous malformation: an observational study using magnetic resonance imaging.

BACKGROUND: Some studies reported that cerebral developmental venous anomaly (DVA) is often concurrent with cavernous malformation (CM). But there is lack of statistical evidence and study of bulk cases. The factors associated with concurrency are still unknown. The purpose of this study was to determine the prevalence of concomitant DVA and CM using observational data on Chinese patients and analyze the factors associated with the concurrency. METHODS: The records of all cranial magnetic resonance imaging (MRI) performed between January 2001 and December 2012 in Beijing Tiantan Hospital were reviewed retrospectively. The DVA and CM cases were selected according to imaging reports that met diagnostic criteria. Statistical analysis was performed using the Pearson chi-square statistic for binary variables and multivariable logistic regression analysis for predictors associated with the concurrent CM. RESULTS: We reviewed a total of 165,230 cranial MR images performed during the previous 12 year period, and identified 1,839 cases that met DVA radiographic criteria. There were 205 patients who presented concomitant CM among the 1,839 DVAs. The CM prevalence in DVA cases (11.1%) was significantly higher than that in the non-DVA cases (2.3%) (P<0.01). In the multivariate analysis, we found that DVAs with three or more medullary veins in the same MRI section (adjusted OR = 2.37, 95% CI: 1.73-3.24), infratentorial DVAs (adjusted OR = 1.71, 95% CI: 1.26-2.33) and multiple DVAs (adjusted OR = 2.08, 95% CI: 1.04-4.16) have a higher likelihood of being concomitant with CM. CONCLUSIONS: CM are prone to coexisting with DVA. There is a higher chance of concurrent CM with DVA when the DVA has three or more medullary veins in the same MRI scanning section, when the DVA is infratentorial, and when there are multiple DVAs. When diagnosing DVA cases, physicians should be alerted to the possibility of concurrent CM.

[The development of the cerebral venous system--from the embryo to the adult definitive structure]. / O desenvolvimento do sistema venoso cerebral--do embrião à estrutura definitiva no adulto.

INTRODUCTION: The human development consists of a continuous process where an uninterrupted pattern of extremely complex repetitive cycles of growth, modulation and modification take place. Despite this extreme complexity, the normal development is ordered by an impressive regularity, namely, in chronological, anatomical, topographic and physiological trends. In some organic systems, this development will not be totally ended by the time of birth. In this situation, further changes will have to take place until the adult definitive pattern is achieved. The cerebral venous system (CVS) is such a paradigm. PURPOSE: The authors pretend to present a synopsis of the specific organogenesis of the cerebral venous system in order to allow a correct interpretation of the vascular structures, recognise the anatomical variations and better comprehend the topographic correlations between neighbouring structures. METHOD AND RESULTS: Following a structured and synthetic order, the main guiding lines of the principal evolutional steps will be presented from the first embryological stages until the final and definitive adult pattern. CONCLUSION: The detailed study of the continuous development stages of the CVS constitutes a fundamental tool for the whole recognition of the anatomical structures, their correct interpretation and detection of possible variants as well as a better comprehension of topographic relationship between neighbouring structures. In other words and following KL Moore, Embryology illuminates anatomy.

A history of our understanding of cerebral vascular development and pathogenesis of perinatal brain damage over the past 30 years.

This article reviews our studies focusing on cerebral vascular development, the pathogenesis of subependymal/intraventricular hemorrhage (SEH/IVH), periventricular leukomalacia (PVL), and pontosubicular neuron necrosis (PSN). Their pathogenesis consists of predisposing developmental and causal factors. SEH/IVH may be caused by reperfusion or overperfusion following ischemia in the subependymal germinal matrix with characteristic vasculature. The cause of PVL is multifactorial (ie, ischemia and inflammation), predisposed by the maturational status of the vasculature and oligodendroglia in the white matter. Focal PVL is ischemic necrosis, and diffuse PVL or white matter injury may include cytotoxic damage. PSN has an apoptotic character, and may be induced by ischemic and oxidative stress on specific immature neurons. Further studies on preventive and therapeutic measures are necessary in clinical, pathologic, and experimental fields. The monitoring and control methods of brain hemodynamics and cellular stability should be more developed to prevent brain damages.

Morphology of the Willis chords in the superior sagittal sinus during various periods of life.

UNLABELLED: Numerous fibrous elements known as the Willis chords are situated in the light of the superior sagittal sinus. The paper is aimed at a comparative evaluation of the appearance of the Willis chords appearing in the superior sagittal sinus during various periods of human life and a determination of their role. The material comprises 200 brains at the foetal period as well as 200 adult and senile brains. The experimental methods include injection methods, infrared light, the Pickworth method and computer image analysis. During adulthood, various elements such as valvulae, divisions, plates, beams and arachnoidal granulation are situated in the light of superior sagittal sinus. The number of arachnoidal granulations increases continuously due to age, new ones appearing close to those already in existence and old granulation spreading. The superior sagittal sinus contains numerous valvulae similar to the feedback flaps typical for hydraulic systems. Divisions act as orifices which lead to a fall in pressure and induce blood into the sinus. Large differences between the cross-sections of meningeal veins and bridge veins were noticed, which resembles the structure of ejector. The blood flow in the bridge veins ending at the superior sagittal sinus is controlled by the valvulae and their geometrical form changes according to age. CONCLUSION: The Willis chords situated in the superior sagittal sinus may control the circulation. Their number grows with age and their morphology changes.

Correlation between cerebrovascular maturity and periventricular leukomalacia.

This study disclosed the close correlation between the characteristic developmental change of human cerebral vessels and the occurrence of periventricular leukomalacia (PVL), as judged by anticollagen type 6 immunohistochemical analysis. The earlier appearance of collagen type 6-positive vessels in the deep white matter supports the concept that the medullary vein, a terminal branch of the internal cerebral vein, develops earlier than the cortical and subcortical veins and the perforating artery because the latter was not stained in early gestation. In cases with an old lesion of PVL the distribution of the lesions with abnormal vessels differed with gestation age. These results suggest that its distribution correlates with the development of perforating medullary arteries. Thus a discrepancy between the arteries, revealing slow maturation, and veins, revealing early maturation, in the deep white matter may be an important predisposing factor for PVL. Furthermore, the widespread lesions of PVL may be closely related to the involvement of transcortical tract damage, in terms of specific motor or intellectual disabilities.

Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1.

Several reports have demonstrated that cerebral blood flow decreases with age and may contribute to neurodegenerative changes found in aging animals and man. Because GH and insulin-like growth factor 1 (IGF-1) decrease with age and have an important role in vascular maintenance and remodeling, we hypothesized that the decrease in cerebral blood flow is associated with a rarefaction of cerebral blood vessels resulting from a decline in GH and IGF-1. Measurements of vascular density (number of vessels/cortical surface area) in both Brown-Norway and Fisher 344/Brown-Norway rats were made at 5, 13, and 29 months of age using chronic cranial window chambers that allowed viewing of the cortical surface and its corresponding vasculature. Correlations were made with plasma levels of IGF-1. In Brown-Norway rats, arteriolar density decreased from 15.53 +/- 1.08 to 9.49 +/- 0.62 endpoints/mm2 in 7- and 29-month-old animals, respectively (P < 0.05). A decline was observed also in arteriolar anastomoses [3.05 +/- 0.21 to 1.42 +/- 0.24 connections/mm2 in 7- and 29-month-old animals (P < 0.05)]. Venular density did not decrease with age. Similar changes were observed in Fisher 344/Brown-Norway rats. The number of cortical surface arterioles was correlated with plasma IGF-1 levels at the time of vascular mapping (r = 0.772, P < 0.05), and injection of bovine GH (0.25 mg/kg, s.c., twice daily for 35 days) to 30-month-old animals increased both plasma IGF-1 and the number of cortical arterioles. These data indicate that: 1) vascular density on the surface of the cortex decreases with age; 2) vascular density is correlated with plasma levels of IGF-1; and 3) injection of GH increases cortical vascular density in older animals. We conclude that GH and IGF-1 have an important role in the decline in vascular density with age and suggest that decreases in vascular density may have important implications for the age-related decline in cerebral blood flow and brain function.

The cranial venous system in the rat: anatomical pattern and ontogenetic development. II. Dorsal drainage.

The precise anatomical pattern and the developmental sequences of the dorsal cranial sinuses are described with special reference to the petrosquamosal sinus. The pattern of the dorsal cranial venous system of the rat is quite similar to that of man, although there are certain important differences. In rats, the transverse sinus bifurcates into the small dorsally directed sigmoid sinus and the large laterally directed petrosquamosal sinus. The latter emerges through the wide petrosquamosal fissure and joins the maxillary and posterior facial veins, sending two roots to each. The superior sagittal sinus anastomoses ventrally with the interperioptic sinus. This pattern is already established at an early developmental stage and is obvious by gestational day E 19. The anlages of the transverse and the sigmoid sinuses are formed from anastomoses between the three dural stems which drain the blood from the brain vesicles via the primary head vein into the anterior cardinal veins. The middle dural stem is connected by a rich capillary network to both the developing maxillary vein and the external jugular venous system before day E 16, thus establishing the anlage of the petrosquamosal sinus. Its definitive pattern is already discernible on day E 18. The external jugular vein becomes the main cranial venous outflow in the postnatal rat.

Development and remodeling of cerebral blood vessels and their flow in postnatal mice observed with in vivo videomicroscopy.

Changes of blood vessels in the mouse somatosensory (barrel) cortex were assessed from birth (P0) to adulthood. Surface vessel anatomy and flow were observed directly with videomicroscopy through closed cranial windows and with intravascular fluorescent tracers. Histology was used to determine the internal capillary density. At birth, arterioles had numerous anastomoses with each other, pial capillaries formed a dense surface plexus, and pial venules and veins were relatively small and irregular. Morphological changes over the next 2 weeks included (a) fewer arteriolar anastomoses, (b) formation and growth of venules, (c) more uniform diameters of all types of vascular segments, (d) increase in intraparenchymal capillary length density (Lv), and (e) decreases in superficial capillary density and diameters. A simple morphological test showed that wall shear rates at arteriolar branch points were matched on average in neonates and adults. Flow characteristics in single vessels were evaluated. In arterioles of like diameters, (a) Vmax, (b) peak wall shear rates, and (c) peak flows were similar at all ages; (d) velocity was very high in occasional arteriovenous (AV) shunts in newborns; and (e) flow in arteriolar anastomoses was slow and variable. Although flow was heterogeneous in all types of vessel, the marked similarities in newborn and adult mice of average peak velocities and calculated wall shear rates in arterioles of the same size suggest that blood flow regulates in part the remodeling of blood vessels during development (Rovainen et al., 1992). The rodent barrel cortex undergoes major neuronal and vascular development, functional differentiation, and remodeling during the first weeks after birth. It provides special opportunities for testing how blood vessels grow and adapt to supply the local metabolic requirements of neural modules in the brain.

[Age-related dynamics of blood supply and vascular-tissue interrelations in the human pineal body]. / Vozrastnaia dinamika krovosnabzheniia i sosudisto-tkanevykh vzaumootnoshenii v shishkovidnom tele u cheloveka.

Thirty-seven pineal bodies have been studied. They have been obtained from persons of both sex at the age of 18 up to 88 years, perished from accidental causes. Specific volumes of the epiphyseal tissues and vascular constructions of all types have been determined in histological preparations. In young age (up to 40-45 years) the volume of the intraorganic epiphyseal vascular bed is greater, and its blood supply is better than in persons of elderly and old age, when the sclerosing process in the organ occurs at the expense of outgrowth of fibrous elements of the connective tissue carcass. During the pineal body involution, the volume of its intraorganic vascular bed decreases essentially. This results in certain disturbances of blood supply and affects functional activity of the organ.