A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

2002 ◽  
Vol 97 (5) ◽  
pp. 1198-1202 ◽  
Author(s):  
Jian Hai ◽  
Meixiu Ding ◽  
Zhilin Guo ◽  
Bingyu Wang

Object. A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure. Methods. Twenty-four Sprague—Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ispilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood—brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy. Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries. Conclusions. The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.

2005 ◽  
Vol 103 (5) ◽  
pp. 882-890 ◽  
Author(s):  
Noboru Kusaka ◽  
Kenji Sugiu ◽  
Koji Tokunaga ◽  
Atsushi Katsumata ◽  
Ayumi Nishida ◽  
...  

Object. Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks. Methods. A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group. Conclusions. In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.


2001 ◽  
Vol 95 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Bernhard Meyer ◽  
Horst Urbach ◽  
Carlo Schaller ◽  
Johannes Schramm

Object. The authors' goal in this study was to challenge the proposed mechanism of the occlusive hyperemia theory, in which it is asserted that stagnating flow in the former feeding arteries of cerebral arteriovenous malformations (AVMs) leads to parenchymal hypoperfusion or ischemia, from which postoperative edema and hemorrhage originate. Methods. Cortical oxygen saturation (SaO2) was measured in 52 patients by using microspectrophotometry in areas adjacent to AVMs before and after resection. The appearance of the former feeding arteries was categorized as normal (Group A); moderately stagnating (Group B); and excessively stagnating (Group C) on postoperative angiographic fast-film series. Patients and SaO2 values were pooled accordingly and compared using analysis of variance and Duncan tests (p < 0.05). Angiographic stagnation times in former feeding arteries were correlated in a linear regression/correlation analysis with SaO2 data (p < 0.05). All values are given as the mean ± standard deviation. The average median postoperative SaO2 in Group C (15 patients) was significantly higher than in Groups B (17 patients) and A (20 patients) (Group C, 75.2 ± 8.5; Group B, 67.5 ± 10.8; Group A, 67.1 ± 12 %SaO2), as was the average postoperative increase in SaO2 (Group C, 25.9 ± 14.9; Group B, 14.6 ± 14; Group A, 11.1 ± 14 %SaO2). Angiographically confirmed stagnation times were also significantly longer in Group C than in Group B (Group C, 5.6 ± 2.5; Group B, 1.3 ± 0.6 seconds). A significant correlation/regression analysis showed a clear trend toward higher postoperative SaO2 levels with increasing stagnation time. Conclusions. Stagnating flow in former feeding arteries does not cause cortical ischemia, but its presence on angiographic studies is usually indicative of hyperperfusion in the surrounding brain tissue after AVM resection. In the context of the pathophysiology of AVMs extrapolations made from angiographically visible shunt flow to blood flow in the surrounding brain tissue must be regarded with caution.


1997 ◽  
Vol 86 (3) ◽  
pp. 519-524 ◽  
Author(s):  
Lali H. S. Sekhon ◽  
Michael K. Morgan ◽  
Ian Spence

✓ Excision of human cerebral arteriovenous malformations (AVMs) can be complicated by postoperative edema and hemorrhage in adjacent brain tissue, despite the complete excision of the malformation. Various theories have purported to explain the hemodynamic basis for this predisposition, including disordered autoregulation causing “normal perfusion pressure breakthrough” and obstruction of venous drainage leading to “occlusive hyperemia.” This study did not evaluate the arterial or venous circulations in this scenario, but rather examined the capillaries in adjacent brain parenchyma for any structural deficiencies that would predispose the brain to the postoperative formation of edema and hemorrhage. Arteriovenous fistulas (AVFs) were created surgically in the necks of 10 male Sprague—Dawley rats, which caused chronic cerebral hypoperfusion with a reduction in cerebral blood flow of between 25% and 50%. Ten age-matched animals were used as controls. Twenty-six weeks after AVF formation the animals were killed and perfusion fixed. Their brain tissue was prepared for light microscopic studies by staining for glial fibrillary acidic protein or for transmission electron microscopy. In the CA1 pyramidal cell region of the hippocampus, it was found that in the animals with AVFs there was increased capillary density and absent astrocytic foot processes in some of these vessels. It was concluded that these vessels had developed as a result of neovascularization in response to chronic cerebral ischemia and that their anatomical configuration made them prone to mechanical weakness and instability following the increase in perfusion pressure that occurs in adjacent brain parenchyma after AVM excision. The authors believe that this study pinpoints a structural accompaniment to the hemodynamic changes that occur in brain tissue in the vicinity of cerebral AVMs that predispose these areas to the formation of edema and hemorrhage after AVM excision.


2005 ◽  
Vol 102 ◽  
pp. 289-292 ◽  
Author(s):  
György T. Szeifert ◽  
Ottó Major ◽  
Andras A. Kemeny

Object.The authors analyzed morphological alterations at the subcellular level by undertaking transmission electron microscopy in arteriovenous malformations (AVMs) after gamma knife surgery (GKS).Methods.Histological, immunohistochemical, and electron microscopic investigations were performed in a series of pathological specimens obtained in seven patients. The patients harbored cerebral AVMs that had been previously treated with GKS and had suffered subsequent bleeding 10 to 52 months after treatment.Histological studies revealed spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. Electron microscopy demonstrated different ultrastructural characteristics of this spindle cell population. There were cells with a smooth-edged oval nuclei surrounded by massive bundles of collagen fibers in the extracellular matrix. Other cells with the same nuclear morphology contained abundant intracytoplasmic filaments. Nuclear deformation was connected to a fibrillary system developed within the cytoplasm, and peripheral attachment sites were related to an extracellular layer of basement membrane—like material arranged parallel to the cell border. Also present were cells containing well-developed cisterns of rough endoplasmic reticulum and dense bodies at the periphery of the cytoplasm with folded, irregular nuclei.Conclusions.The ultrastructural and histological characteristics of the spindle cell population in the GKS-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Because similar cell modifications have not been demonstrated in control nonirradiated AVM specimens, these myofibroblasts may contribute to the shrinking process and final occlusion of AVMs after radiosurgery.


1977 ◽  
Vol 47 (3) ◽  
pp. 442-450 ◽  
Author(s):  
Marco A. Lana-Peixoto ◽  
Julio Lagos ◽  
Shirley W. Silbert

✓ Pigmented carcinoma of the choroid plexus was found in a 33-year-old man. Autopsy revealed no primary tumor in the skin or eyes. A slightly cystic pigmented tumor was present in the right lateral ventricle infiltrating the thalamus and striatum. Metastatic implants were found in both temporal lobes and the cerebellum. The spinal cord was covered by black meningeal nodules, and the cauda equina was completely encased by the tumor. Metastases were found in the liver, pancreas, and kidney. Microscopically the mass contained normal choroid plexus with psammoma bodies adjacent to carcinomatous epithelium forming prominent papillae and tubules. Melanin granules were found within the neoplastic cells and in the stroma. Electron microscopy demonstrated melanin granules in various stages of development in the cells, which were joined one to another by desmosome-like structures. This is the second reported case of pigmented carcinoma of the choroid plexus and the first with metastases outside the central nervous system.


1989 ◽  
Vol 71 (6) ◽  
pp. 932-934 ◽  
Author(s):  
Naoya Kuwayama ◽  
Akira Takaku ◽  
Michiharu Nishijima ◽  
Shunro Endo ◽  
Masato Hirao

✓ Two cases of multiple dural arteriovenous malformations (AVM's) in different locations are reported. One patient was diagnosed as having a dural AVM involving the right cavernous sinus that disappeared spontaneously 4 months after onset of symptoms. After an interval of 4 months, another dural AVM appeared involving the right lateral sinuses (transverse and sigmoid sinuses) with occlusion of the right sigmoid sinus. In the other patient, multiple dural AVM's were demonstrated on angiography, one involving the cavernous sinus and the other the left lateral sinus. The frequency of multiple occurrence and possible mechanisms of sinus occlusion are discussed.


1991 ◽  
Vol 75 (6) ◽  
pp. 856-864 ◽  
Author(s):  
Fernando Viñuela ◽  
Jacques E. Dion ◽  
Gary Duckwiler ◽  
Neil A. Martin ◽  
Pedro Lylyk ◽  
...  

✓ The authors describe their experience with 101 cerebral arteriovenous malformations (AVM's) treated by endovascular embolization followed by surgical removal. Fifty-three patients presented with intracranial hemorrhage and 35 had seizures. Based on the classification of Spetzler and Martin, two AVM's were Grade I, 13 were Grade II, 26 were Grade III, 43 were Grade IV, and 17 were Grade V, Fifty-six AVM's were in the right hemisphere, 28 were in the left hemisphere, 12 were in the corpus callosum, and five involved the cerebellum. In 50 cases, presurgical obliteration of 50% to 75% of the AVM nidus was achieved by embolization, and in 31 cases this percentage increased to between 75% and 90%. In 97 (96%) patients, complete surgical removal of the AVM was obtained. Morbidity resulting from preoperative endovascular embolization was classified as mild in 3.9% of the cases, moderate in 6.9%, and severe in 1.98%. The death rate related to embolization was 0.9%. The immediate postsurgical morbidity was classified as mild in 5.9% of the cases, moderate in 10.8%, and severe in 5.9%. The overall long-term morbidity was mild in 5.9% of the cases, moderate in 6.9%, and severe in 1.98%. Two patients (1.98%) died due to intractable intraoperative hemorrhage and two (1.98%) as a result of postsurgical pulmonary complications.


2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 289-292 ◽  
Author(s):  
György T. Szeifert ◽  
Ottó Major ◽  
Andras A. Kemeny

Object. The authors analyzed morphological alterations at the subcellular level by undertaking transmission electron microscopy in arteriovenous malformations (AVMs) after gamma knife surgery (GKS). Methods. Histological, immunohistochemical, and electron microscopic investigations were performed in a series of pathological specimens obtained in seven patients. The patients harbored cerebral AVMs that had been previously treated with GKS and had suffered subsequent bleeding 10 to 52 months after treatment. Histological studies revealed spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. Electron microscopy demonstrated different ultrastructural characteristics of this spindle cell population. There were cells with a smooth-edged oval nuclei surrounded by massive bundles of collagen fibers in the extracellular matrix. Other cells with the same nuclear morphology contained abundant intracytoplasmic filaments. Nuclear deformation was connected to a fibrillary system developed within the cytoplasm, and peripheral attachment sites were related to an extracellular layer of basement membrane—like material arranged parallel to the cell border. Also present were cells containing well-developed cisterns of rough endoplasmic reticulum and dense bodies at the periphery of the cytoplasm with folded, irregular nuclei. Conclusions. The ultrastructural and histological characteristics of the spindle cell population in the GKS-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Because similar cell modifications have not been demonstrated in control nonirradiated AVM specimens, these myofibroblasts may contribute to the shrinking process and final occlusion of AVMs after radiosurgery.


1993 ◽  
Vol 78 (2) ◽  
pp. 176-182 ◽  
Author(s):  
Michael K. Morgan ◽  
Ian H. Johnston ◽  
John M. Hallinan ◽  
Neville C. Weber

✓ A series of 112 patients undergoing complete surgical resection of arteriovenous malformations (AVM's) of the brain between 1974 and 1990 were analyzed for complications and 12-month outcomes. The cohort consisted of 44 patients with small AVM's (< 2 cm in diameter), 43 patients with medium-sized AVM's (2 to 4 cm in diameter), and 25 patients with large AVM's (> 4 cm in diameter). There was a 3.6% series mortality rate and an 18% morbidity rate. One of the four deaths was caused by normal perfusion pressure breakthrough. Analysis of logistic regression found that the most important factor influencing the occurrence of complications in this series was AVM size (p = 0.005) and that the occurrence of complications (p < 0.001) and the neurological grade at the time of surgery (p < 0.004) both significantly contributed to the outcome at 12 months. This study stresses the importance of defining complications in terms of rigid criteria when analyzing AVM series in order to allow for a correct evaluation of the risk:benefit ratio of surgery. Furthermore, it emphasizes the need for a separate analysis of the importance of complications upon outcome.


2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 113-119 ◽  
Author(s):  
D. Hung-Chi Pan ◽  
Wan-Yuo Guo ◽  
Wen-Yuh Chung ◽  
Cheng-Ying Shiau ◽  
Yue-Cune Chang ◽  
...  

Object. A consecutive series of 240 patients with arteriovenous malformations (AVMs) treated by gamma knife radiosurgery (GKS) between March 1993 and March 1999 was evaluated to assess the efficacy and safety of radiosurgery for cerebral AVMs larger than 10 cm3 in volume. Methods. Seventy-six patients (32%) had AVM nidus volumes of more than 10 cm3. During radiosurgery, targeting and delineation of AVM nidi were based on integrated stereotactic magnetic resonance (MR) imaging and x-ray angiography. The radiation treatment was performed using multiple small isocenters to improve conformity of the treatment volume. The mean dose inside the nidus was kept between 20 Gy and 24 Gy. The margin dose ranged between 15 to 18 Gy placed at the 55 to 60% isodose centers. Follow up ranged from 12 to 73 months. There was complete obliteration in 24 patients with an AVM volume of more than 10 cm3 and in 91 patients with an AVM volume of less than 10 cm3. The latency for complete obliteration in larger-volume AVMs was significantly longer. In Kaplan—Meier analysis, the complete obliteration rate in 40 months was 77% in AVMs with volumes between 10 to 15 cm3, as compared with 25% for AVMs with a volume of more than 15 cm3. In the latter, the obliteration rate had increased to 58% at 50 months. The follow-up MR images revealed that large-volume AVMs had higher incidences of postradiosurgical edema, petechiae, and hemorrhage. The bleeding rate before cure was 9.2% (seven of 76) for AVMs with a volume exceeding 10 cm3, and 1.8% (three of 164) for AVMs with a volume less than 10 cm3. Although focal edema was more frequently found in large AVMs, most of the cases were reversible. Permanent neurological complications were found in 3.9% (three of 76) of the patients with an AVM volume of more than 10 cm3, 3.8% (three of 80) of those with AVM volume of 3 to 10 cm3, and 2.4% (two of 84) of those with an AVM volume less than 3 cm3. These differences in complications rate were not significant. Conclusions. Recent improvement of radiosurgery in conjunction with stereotactic MR targeting and multiplanar dose planning has permitted the treatment of larger AVMs. It is suggested that gamma knife radiosurgery is effective for treating AVMs as large as 30 cm3 in volume with an acceptable risk.


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