Kenji Yatomi

Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia–reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.

Surgical considerations in fourth ventricular ependymoma with the transcerebellomedullary fissure approach in focus.

IntroductionWithin the existing consensus for the best management of pediatric infratentorial ependymomas (PIE), surgery is the most important stage, where complete removal should be the perfect aim, before complementing it with chemo- or radiotherapy. That, however, remains a challenge even for the most skillful surgeons because of the vicinity of important brainstem and cranial nerve structures involved and is particularly difficult in lateral extensions.Materials and methodsThe paper analyzes the current trends of PIE treatment with emphasis on resection difficulties created by lateral extensions. Anatomical analysis and clinical application of the cerebellomedullary fissure dissection has created specific approaches, providing safe route to the lateral recess and cerebellopontine area by dividing safely tenia and tonsils and biventer lobes retraction.Discussion and conclusionBilateral and unilateral approaches have been developed. This approach prevents the damage of transvermian access and the resulting cerebellar mutism in some cases. Indications, technique and benefits of transcerebellomedullary fissure types of approaches are discussed.

Pathophysiological dual action of adiponectin after transient focal ischemia in mouse brain.

BACKGROUND Adiponectin, an adipocyte-derived bioactive protein, provides vascular protection. Recent clinical studies have suggested that plasma adiponectin plays a role in cerebrovascular disease (CVD). The present study was designed to determine the serial changes in adiponectin expression in the brain and plasma after transient focal cerebral ischemia in mice. METHODS C57BL/6 mice (n=100) were subjected to 60 min of middle cerebral artery occlusion followed by 1, 3, 6, 12, 24, 48, 72 h and 7-day reperfusion. Plasma adiponectin levels were determined by ELISA kit, and expression of adiponectin was assessed by immunohistochemistry, western blot analysis, and reverse transcription-polymerase chain reaction. RESULTS Cerebral ischemia-reperfusion injury resulted in a transient rise in the acute phase and decrease in the late phase, in plasma adiponectin levels (P<0.05). The same insult resulted in upregulation of adiponectin expression, with two peaks at 3 and 24 h after reperfusion (P<0.05). Adiponectin protein was negligible in nonischemic contralateral hemispheres, but relatively high levels of the protein were detected in the ischemic hemisphere. Adiponectin mRNA was detected in neither nonischemic nor ischemic hemisphere. Adiponectin accumulated only in endothelial cells of ischemic brain in response to cerebral ischemia. CONCLUSIONS Our results indicate that ischemic insult results in a transient rise in plasma adiponectin level during the acute phase, and that circulating adiponectin then accumulates in damaged vessels in the ischemic brain during the late phase. These findings suggest that time-targeting administration of adiponectin could be potentially useful in the treatment of stroke.

Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.

Radiological changes in infantile dissecting anterior communicating artery aneurysm treated endovascularly. A case report and five-year follow-up.

Intracranial aneurysms are extremely rare in infants, and to our knowledge only seven infants treated for ruptured spontaneous dissecting aneurysms have been reported. Good outcomes have been achieved with endovascular treatment of infantile aneurysm. We the endovascular treatment of a one-month-old girl for ruptured dissecting aneurysm located in the anterior communicating artery, and the unique radiological changes that were observed during the perioperative and follow-up periods. These changes suggest that blood coagulation and fibrinolytic response play a part in the repair and healing processes of dissecting aneurysms. Careful neuroradiological surveys are needed for pediatric dissecting aneurysms treated endovascularly.

New Experimental Model of Terminal Aneurysms in Swine: Technical Note

BACKGROUND Animal models of intracranial aneurysms are important for training surgeons and creating innovative endovascular treatment. Swine have physical dimensions close to those of humans and so are widely used in cardiology research. swine used as models for intracranial aneurysms have had difficulty maintaining long-term aneurysm patency. We present a swine model that may allow researchers to follow long-term outcomes after endovascular treatment. MATERIALS AND METHODS We developed a terminal aneurysm model in swine (n = 3) using a vein pouch of an end-to-side anastomosis of the right carotid artery. We anastomosed the left carotid artery end and the right carotid artery side, designing it so the blood flows into the aneurysmal neck directly from the opposite side. we also anastomosed the ascending cervical artery and the right carotid artery, with flow reversal in the proximal right carotid artery by ligating the more proximal side. At the same time, a side-wall aneurysm was made, and we compared their patency periods. RESULTS The terminal aneurysms remained patent for 3 months, and there were no major changes in their size or shape. In contrast, the side-wall aneurysms had become occluded at the 1-month follow-up. CONCLUSION Our swine model displayed long-term patency and has the potential to allow long-term evaluation of new techniques and embolic agents.

Bipolar Cutting Method: Another Technique for Harvesting Donor Artery With Histological Investigation

BACKGROUND Safe and appropriate harvesting of the donor scalp vessel is the first key procedure in any type of bypass surgery. OBJECTIVE To use the so-called bipolar cutting method to harvest donor arteries, in which the donor arteries are skeletonized with bipolar cautery. The surgical procedure and the preparation of the equipment of the bipolar cutting method are described. The surgical results and histological assessment are presented. METHODS The bipolar generator was set at 50 Malis units in the coagulation mode. Under the surgical microscope, the surrounding tissue of the donor artery was divided and coagulated with the bipolar forceps. The donor artery was completely skeletonized to provide adequate length. After the recipient artery was chosen and the anastomosis site was decided, the distal end of the donor artery was cut to the appropriate length. The remnant fragment of the donor artery was histologically investigated for any damage to the arterial wall. The specimen was cut longitudinally to observe the entire length of the arterial wall and stained with hematoxylin and eosin and elastica van Gieson. RESULTS A total of 30 bypass surgeries were performed and 38 histological specimens were obtained between February 2015 and June 2016. The success rate of the bypass was 96%. No arterial wall damage such as thermal injury or dissection of the wall was recognized in any of the specimens. CONCLUSION The bipolar cutting method is a useful and safe method for harvesting donor scalp artery.

Flow Diverter Therapy Using a Pipeline Embolization Device for 100 Unruptured Large and Giant Internal Carotid Artery Aneurysms in a Single Center in a Japanese Population

Flow diverters (FDs) have been developed for intracranial aneurysms difficult to treat with conventional endovascular therapy and surgical clipping. We reviewed 94 patients with 100 large or giant unruptured internal carotid artery (ICA) aneurysms treated with Pipeline embolization device (PED) embolization from December 2012 to June 2017 at Juntendo University Hospital. The patients’ mean age was 63.4 years (range, 19–88), and there were 90 women 89.4%. Aneurysm locations were: C4 (45), C3 (4), and C2 (51) in ICA segments. Mean aneurysm size and neck width were 16.9 ± 6.8 mm and 8.3 ± 4.4 mm, respectively, in 40 symptomatic and 60 asymptomatic aneurysms. Follow-up catheter angiographies of 85 patients with 90 aneurysms showed no filling in 62 aneurysms (68.9%), entry remnant in 16 (17.8%), subtotal filling in 11 (12.2), and total filling in 1 (1.1%) with a mean follow-up of 10.2 ± 5.6 months. In-stent stenosis occurred in 1 patient and parent artery occlusion in 2 during follow-up. Hemorrhagic complications occurred in 4 (4.3%): delayed aneurysm rupture (2) and intraparenchymal hemorrhage (2). Ischemic complications with neurological symptoms occurred in 2 (2.1%): very delayed device occlusion (1) and intraprocedural distal embolism (1). Eighteen patients (45%) showed improvement in pre-existing cranial nerve dysfunction because of the aneurysm’s mass effect, 3 patients (7.5%) worsened. One patient died of systemic organ failure unassociated with the procedure. Morbidity and mortality rates were 4.3% and 1.1%, respectively. PED embolization for unruptured large and giant ICA aneurysms is safe and efficacious. Physicians should be observant of characteristic risks associated with FD therapy.

Transvenous Aneurysm Sac and Rupture Point Coil Embolization of Direct Carotid Cavernous Fistula after Pipeline Embolization

A delayed aneurysm rupture after flow diverter therapy is a rare but serious complication. Due to the anatomical specificity, a delayed rupture of a carotid cavernous aneurysm may cause a direct carotid cavernous fistula (dCCF). We present a novel therapeutic approach for treatment of dCCF after flow diverter therapy using the Pipeline embolization device (PED). An 86-year-old woman suffered from dCCF after PED embolization. A microcatheter was advanced through the transvenous approach into the cavernous sinus (CS) and further inserted into the aneurysm sac via the rupture point. Coil embolization of both the aneurysm sac and a small part of the CS adjacent to the fistulous site could achieve not only the immediate aneurysm occlusion but also the rupture point obliteration with a small amount of coil mass in the CS.

Differences in tissue proliferation and maturation between Matrix2 and bare platinum coil embolization in experimental swine aneurysms

BACKGROUND AND PURPOSE Recanalization of post-embolization cerebral aneurysms remains a serious problem that influences treatment outcomes. Matrix2 is a bioactive, bio-absorbable, detachable coil that was developed to reduce the risk of recanalization. We examined the short-term efficacy of the Matrix2 coil system, and evaluated the temporal profile of tissue proliferation in a swine experimental aneurysm model compared with the bare platinum (BP) coil. MATERIALS AND METHODS Thirty-six experimental aneurysms were created in 18 swine. All aneurysms were tightly packed with Matrix2 or BP coils. Comparative histologic and morphologic analyses were undertaken 1, 2 and 4 weeks post-embolization. RESULTS Endothelial-like cells were observed partially lining the aneurysmal opening one week post-embolization with both coil types. At two and four weeks post-embolization, the aneurysms treated with Matrix2 coils had more extensive areas of organized thrombus than those packed with BP coils, but the numbers of functional proliferating endothelial cells identified by immunohistochemistry in the tissue were broadly comparable between the groups. Moreover, morphological analysis suggested there were more mature endothelial cells in aneurysms treated with bare platinum rather than Matrix2 coils. CONCLUSIONS Our results indicate that aneurysms embolized with Matrix2 coils build thicker scaffolds for endothelialization, but this is not necessarily evidence of earlier tissue proliferation and maturation than those embolized with BP coils. Matrix2 coils may not be superior to BP coils for preventing aneurysmal recanalization after endovascular treatment of cerebral aneurysms.