Non-aneurysmal subarachnoid hemorrhage in aplastic or twig-like middle cerebral artery: A case report and literature review.

BACKGROUND: Aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare vascular anomaly that can cause hemorrhagic and ischemic stroke. Ap/T-MCA can induce aneurysms due to the fragility of the vessel wall, consequently leading to subarachnoid hemorrhage. Herein, we report a case of Ap/T-MCA with subarachnoid hemorrhage without an aneurysm. CASE PRESENTATION: A 67-year-old man presented to our hospital with a sudden onset of headache. Computed tomography of the head revealed subarachnoid hemorrhage (SAH) in the left Sylvian fissure; however, no aneurysm was observed on digital subtraction angiography. Following conservative treatment, follow-up imaging showed no aneurysm or no recurrent stroke. CONCLUSION: Non-aneurysmal SAH is a possible indication of vessel wall fragility in Ap/T-MCA; however, a standardized treatment strategy for this condition remains to be established.

A Case of Tracheo-innominate Artery Fistula after Tracheostomy Successfully Treated with a Covered Stent.

A 78-year-old man underwent a tracheostomy after embolization for a dural arteriovenous fistula. Seventy days after tracheostomy, arterial bleeding appeared through the tracheal stoma. The bleeding stopped spontaneously. However, two days later, arterial bleeding reappeared, and he was diagnosed with a tracheo-innominate artery fistula (TIF). He then underwent urgent endovascular covered stent placement. After the procedure, there was no bleeding. TIF can be a fatal complication after tracheostomy and it is generally treated with open chest surgery. However, a successful endovascular treatment for TIF has recently been reported and may yield better results.

A case of simple stenting for ruptured basilar perforator aneurysm.

Ruptured aneurysms in perforating arteries are uncommon. We report a case of a basilar perforator artery aneurysm that was treated successfully using simple stenting to induce a rectifying effect without using a coil. In this case, coiling for the aneurysm was attempted initially, but it failed because of anatomical and practical problems. After placement of two stents in the basilar artery, the aneurysm was occluded completely without any neurological deficits at 100 days after the procedure. Although superselective coil embolization is ideal even in a small perforator aneurysm, simple stenting for a parent artery is a preferable treatment, especially in challenging cases for coil embolization of the aneurysmal dome.

A Case of Brainstem Infarction That Was Found to Be Vertebral Artery Dissection in a Short Period after the Diagnosis of Atherothrombotic Infarction.

Objective: We report a case of vertebral artery dissecting aneurysm that caused right lateral medullary infarction, which was treated by endovascular therapy. Case Presentations: A 57-year-old man developed right-side headache and dysarthria on the day before presentation, and exhibited mouth dropping and dysphagia the following day. Initial MRI demonstrated right lateral medullary infarction with atherothrombotic change with no vessel lesion, and we started infusion and medication administration. Later MRI revealed bilateral vertebral artery dissection, and we treated the growing right vertebral artery dissecting aneurysm by stenting and coils. Conclusion: The possibility of dissecting lesions should be considered in cases of medullary infarction. Stenting and coil treatment is a useful option for bilateral dissecting vertebral aneurysms.

[A Case of Arteriovenous Malformation of the Parotid Gland Associated with Cowden Disease].

We report a rare case of arteriovenous malformation(AVM)of the parotid gland associated with Cowden disease successfully treated with preoperative embolization followed by surgical removal. A 39-year-old man with a history of Cowden disease presented with a pulsating and growing mass on his left lower jaw. Contrast-enhanced computed tomography(CT)and angiography revealed a high-flow AVM in the deep lobe of the left parotid gland. After intravascular embolization of the feeding arteries, surgery was performed using the NIM-response®3.0, facial nerve monitoring system. The AVM was almost completely removed and the facial nerves were morphologically preserved. Interestingly, the intraoperative findings revealed that the enlarged vasa nervorum of the facial nerve also fed the AVM. Although left facial nerve palsy appeared after the surgery, the nerve function gradually improved over one year. No recurrence of the AVM has been observed for one year.

Coronary Subclavian Steal Syndrome Successfully Treated with Subclavian Artery Stenting: A Report of 2 Cases.

Coronary subclavian steal syndrome (CSSS) is a well-recognized phenomenon secondary to coronary artery bypass grafting and may cause myocardial ischemia. We report 2 cases of CSSS successfully treated with subclavian artery (SA) stenting. In both cases, an Optimo balloon guiding catheter was placed in the SA immediately proximal to the vertebral artery (VA) origin as a double protection system for the VA and left internal thoracic artery (LITA) graft. There were no periprocedural complications. Balloon protection for both the VA and LITA using a single balloon guiding catheter is a reasonable and safe technique for preventing distal embolisms.

Stenting for Internal Carotid Artery Stenosis Associated with Persistent Primitive Hypoglossal Artery Using Proximal Flow Blockade and Distal Protection System: A Technical Case Report and Literature Review.

We report a very rare case of internal carotid artery (ICA) stenosis associated with persistent primitive hypoglossal artery (PPHA) treated by stenting using a proximal flow blockade and distal filter protection system. A 77-year-old man with a medical history of repeated cerebral infarction was referred to our hospital for treatment of progressive ICA stenosis. Cerebral angiography revealed that the degree of stenosis was 50% and the PPHA branched just distal to the stenosis at the C2 vertebral level. Black-blood magnetic resonance imaging indicated vulnerable plaque. The stenosis was at a high location, so carotid artery stenting was employed. Under the proximal flow blockade system with occlusion of the external and common carotid artery, distal filter protection was placed in the ICA to prevent distal embolization. A self-expanding stent was successfully deployed and the patient was discharged without any neurological deficits. In stenting for the ICA stenosis associated with PPHA, the combination of a proximal flow blockade and distal protection system is reasonable and safe.

Role of VEGF and matrix metalloproteinase-9 in peritumoral brain edema associated with supratentorial benign meningiomas.

Accumulating evidence indicates that VEGF and matrix metalloproteinase-9 (MMP-9) play a central role in the development of peritumoral brain edema (PTBE) associated with human brain tumors. However, the roles of these proteins, particularly of MMP-9, in PTBE associated with benign meningiomas have not been elucidated. We investigated the association between clinical features and biological factors, such as VEGF and MMP-9, and the incidence of PTBE and edema index (EI) in 60 patients with benign meningiomas. In this study, supratentorial lesions were examined for evaluating the extent of PTBE in the surrounding normal brain tissue. VEGF and MMP-9 expression was immunohistochemically examined. Multivariate analysis revealed that the presence of pial blood supply (odds ratio [OR] 12.250; P = 0.0096) and VEGF (OR 7.683; P = 0.0155), but not MMP-9 (OR 1.178; P = 0.8113), expression are significant factors that independently predict the incidence of PTBE and influence EI. VEGF (P = 0.0397) and MMP-9 (P = 0.0057) expression correlates with the presence of pial blood supply. Moreover, tumors with high VEGF and MMP-9 expression had higher EIs than those with high expression of either (P = 0.030). Our findings suggest that MMP-9 expression was positively related to VEGF expression and pial blood supply and promoted the occurrence of PTBE by inducing the disruption of the arachnoid membrane and formation of pial blood supply.

Alterations in hippocampal neurogenesis following traumatic brain injury in mice.

Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dcx) up to 14 days after TBI. Dying cells were seen 6 h after injury, peaked at 24 h and returned to control levels at 14 days. Proliferating cells were decreased on the ipsilateral and contralateral sides at all the time points studied except 48 h after injury when a transient increase was seen. Simultaneously, immature neurons were reduced up to 84% relative to controls on the ipsilateral side. In the first week post-TBI, reduced numbers of Dcx-positive cells were also seen in the contralateral side; a return to control levels occurred at 14 days. To determine if these changes translated into longer-term effects, BrdU was administered 1 week post-injury and 3 weeks later the phenotypes of the newly born cells were assessed. TBI induced decreases in the numbers of BrdU-positive cells and new neurons (BrdU/NeuN) on the ipsilateral side without apparent changes on the contralateral side, whereas astrocytes (BrdU/GFAP) were increased on the ipsilateral side and activated microglia (BrdU/CD68) were increased on both ipsi- and contralateral sides. No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impairment.

Depletion of neural precursor cells after local brain irradiation is due to radiation dose to the parenchyma, not the vasculature.

The underlying mechanisms associated with radiation-induced cognitive impairments remain elusive but may involve changes in hippocampal neural precursor cells. Proliferating neural precursor cells have been shown to be extremely sensitive to X rays, either from damage to the cells themselves and/or through microenvironmental factors, including the anatomical relationship with the microvasculature, which is altered by radiation. The neutron capture reaction in boron was used to determine whether the sensitivity of neural precursor cells was dominated by direct radiation effects or was mediated through changes in the microvasculature. Young adult rats were irradiated with X rays, neutrons only, or neutrons plus either mercapto-undecahydro-dodecaborane (BSH) or p-dihydroxyboryl-phenylalanine (BPA). BSH remains inside cerebral vessels, thereby limiting the neutron capture intravascularly; BPA readily passes into the parenchyma. One month after irradiation, cell proliferation and numbers of immature neurons were determined using immunohistochemistry. Results showed that (1) neural precursor cells and their progeny were decreased in a dose-dependent manner by mixed high- and low-LET radiation, and (2) selective irradiation of the microvasculature resulted in less loss of neural precursor cells than when the radiation dose was delivered uniformly to the parenchyma. This information, and in particular the approach of selectively irradiating the vasculature, may be useful in developing radioprotective compounds for use during therapeutic irradiation.

High-LET radiation induces inflammation and persistent changes in markers of hippocampal neurogenesis.

Exposure to heavy-ion radiation is considered a potential health risk in long-term space travel. It may result in the loss of critical cellular components in complex systems like the central nervous system (CNS), which could lead to performance decrements that ultimately could compromise mission goals and long-term quality of life. Specific hippocampal-dependent cognitive impairment occurs after whole-body 56Fe-particle irradiation, and while the pathogenesis of this effect is not yet clear, it may involve damage to neural precursor cells in the hippocampal dentate gyrus. We irradiated mice with 1-3 Gy of 12C or 56Fe ions and 9 months later quantified proliferating cells and immature neurons in the dentate subgranular zone (SGZ). Our results showed that reductions in these cells were dependent on the dose and LET. When compared with data for mice that were studied 3 months after 56Fe-particle irradiation, our current data suggest that these changes are not only persistent but may worsen with time. Loss of precursor cells was also associated with altered neurogenesis and a robust inflammatory response. These results indicate that high-LET radiation has a significant and long-lasting effect on the neurogenic population in the hippocampus that involves cell loss and changes in the microenvironment.

Indicators of hippocampal neurogenesis are altered by 56Fe-particle irradiation in a dose-dependent manner.

The health risks to astronauts exposed to high-LET radiation include possible cognitive deficits. The pathogenesis of radiation-induced cognitive injury is unknown but may involve loss of neural precursor cells from the subgranular zone (SGZ) of the hippocampal dentate gyrus. To address this hypothesis, adult female C57BL/6 mice received whole-body irradiation with a 1 GeV/nucleon iron-particle beam in a single fraction of 0, 1, 2 and 3 Gy. Two months later mice were given BrdU injections to label proliferating cells. Subsequently, hippocampal tissue was assessed using immunohistochemistry for detection of proliferating cells and immature neurons. Routine histopathological methods were used to qualitatively assess tissue/cell morphology in the hippocampal formation and adjacent areas. When compared to controls, irradiated mice showed progressively fewer BrdU-positive cells as a function of dose. This observation was confirmed by Ki-67 immunostaining in the SGZ showing reductions in a dose-dependent fashion. The progeny of the proliferating SGZ cells, i.e. immature neurons, were visualized by doublecortin staining and were significantly reduced by irradiation, with the decreases ranging from 34% after 1 Gy to 71% after 3 Gy. Histopathology showed that in addition to cell changes in the SGZ, (56)Fe particles induced a chronic and diffuse astrocytosis and changes in pyramidal neurons in and around the hippocampal formation. The present data provide the first evidence that high-LET radiation has deleterious effects on cells associated with hippocampal neurogenesis.

Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice.

Advances in the management of pediatric brain tumors have increased survival rates in children, but their quality of life is impaired due to cognitive deficits that arise from irradiation. The pathogenesis of these deficits remains unknown, but may involve reduced neurogenesis within the hippocampus. To determine the acute radiosensitivity of the dentate subgranular zone (SGZ), 21-day-old C57BL/J6 male mice received whole brain irradiation (2-10 Gy), and 48 h later, tissue was assessed using immunohistochemistry. Proliferating SGZ cells and their progeny, immature neurons, were decreased in a dose-dependent fashion. To determine if acute changes translated into long-term alterations in neurogenesis, mice were given a single dose of 5 Gy, and 1 or 3 months later, proliferating cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Confocal microscopy was used to determine the percentage of BrdU-labeled cells that showed mature cell phenotypes. X-rays significantly reduced the production of new neurons at both time points, while glial components showed no change or small increases. Measures of activated microglia and infiltrating, peripheral monocytes indicated that reduced neurogenesis was associated with a chronic inflammatory response. Three months after irradiation, changes in neurogenesis were associated with spatial memory retention deficits determined using the Morris water maze. Behavioral training and testing increased the numbers of immature neurons, most prominently in irradiated animals. These data provide evidence that irradiation of young animals induces a long-term impairment of SGZ neurogenesis that is associated with hippocampal-dependent memory deficits.

Apoptosis induction with 5-fluorocytosine/cytosine deaminase gene therapy for human malignant glioma cells mediated by adenovirus.

Previously, we evaluated the therapeutic efficacy of the adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for malignant gliomas. However, the molecular pathways that mediate the 5-FC/CD gene therapy-induced cell death remains to be elucidated. In this study, we examined the induction of apoptosis and the role of caspases in 5-FC/CD gene therapy using human malignant glioma cells [Gli36delta5 (mutated p53) and U87MG (wild p53)]. The treatment with 5-FC/CD gene-therapy-induced apoptosis both in Gli36delta5 cells and in U87MG cells according to flow cytometric analysis. Immunoblot analysis revealed that caspases 3 and 9 were processed in response to 5-FC/CD in a concentration- and time-dependent manner, but caspase 8 was not. Each caspase 3 and 9 inhibitor significantly reduced apoptosis triggered by 5-FC/CD, but the caspase 8 inhibitor did not affect apoptosis induction. 5-FC/CD significantly promoted the release of cytochorme c from mitochondria in a concentration-dependent manner. These results indicate that 5-FC/CD gene therapy induces apoptosis in human malignant glioma cells and that the apoptotic cell death is mediated by the activation of mitochondrial caspase cascades involving caspases 3 and 9. This is the first report concerning the apoptotic mechanism of 5-FC/CD gene therapy, and these findings could be used to increase the efficacy of suicide gene therapy systems for the treatment of malignant glioma.

Radiation response of neural precursor cells: linking cellular sensitivity to cell cycle checkpoints, apoptosis and oxidative stress.

Therapeutic irradiation of the brain can cause a progressive cognitive dysfunction that may involve defects in neurogenesis. In an effort to understand the mechanisms underlying radiation-induced stem cell dysfunction, neural precursor cells isolated from the adult rat hippocampus were analyzed for acute (0-24 h) and chronic (3-33 days) changes in apoptosis and reactive oxygen species (ROS) after exposure to X rays. Irradiated neural precursor cells exhibited an acute dose-dependent apoptosis accompanied by an increase in ROS that persisted over a 3-4-week period. The radiation effects included the activation of cell cycle checkpoints that were associated with increased Trp53 phosphorylation and Trp53 and p21 (Cdkn1a) protein levels. In vivo, neural precursor cells within the hippocampal dentate subgranular zone exhibited significant sensitivity to radiation. Proliferating precursor cells and their progeny (i.e. immature neurons) exhibited dose-dependent reductions in cell number. These reductions were less severe in Trp53-null mice, possibly due to the disruption of apoptosis. These data suggest that the apoptotic and ROS responses may be tied to Trp53-dependent regulation of cell cycle control and stress-activated pathways. The temporal coincidence between in vitro and in vivo measurements of apoptosis suggests that oxidative stress may provide a mechanistic explanation for radiation-induced inhibition of neurogenesis in the development of cognitive impairment.

The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas.

We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 +/- 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 +/- 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 +/- 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 +/- 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.