Akihito Hashiguchi

Up-Regulation of Endothelial Nitric Oxide Synthase via Phosphatidylinositol 3-Kinase Pathway Contributes to Ischemic Tolerance in the CA1 Subfield of Gerbil Hippocampus

We here investigated endothelial nitric oxide synthase (eNOS) expression after 10 minutes of forebrain ischemia. Real-time polymerase chain reaction, immunoblots and immunohistochemical studies revealed up-regulation of eNOS expression in the hippocampal CA1 subfield of gerbil. Immunoreactivity of eNOS significantly increased in endothelium but neither in neurons nor astrocytes after 6 to 168 hours of reperfusion. An increased Akt activity preceded the postischemic eNOS up-regulation. Intracerebroventricular injection (i.c.v.) of wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI-3K), significantly inhibited the increases in both eNOS mRNA and its protein with concomitant inhibition of Akt activation. The significant increase in the eNOS expression was also evident following preconditioning 2-minute ischemia. Both eNOS up-regulation and acquisition of ischemic tolerance observed at 3 days after preconditioning ischemia were significantly inhibited by pretreatment with wortmannin. Administration (i.c.v.) of NG-nitro-L-arginine methyl ester, but not 7-nitroindazole, 30 minutes prior to lethal 10-minute ischemia, significantly abolished the acquired tolerance. Intraperitoneal injections of aminoguanidine at immediately after, 24, and 48 hours after preconditioning had no effects on the tolerance. These results suggest that eNOS expression is up-regulated in the endothelium via PI-3K pathways after transient forebrain ischemia, and that preconditioning-induced eNOS expression plays an important role in neuroprotection in the ischemic tolerance.

The neuroprotective effect of a novel calmodulin antagonist, 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, in transient forebrain ischemia.

A novel calmodulin (CaM) antagonist DY-9760e, (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate), with an apparent neuroprotective effect in vivo, potently inhibits CaM-dependent nitric oxide synthase in situ. In the present study, we determined whether DY-9760e inhibits nitric oxide (NO) production and protein nitration by peroxynitrite (ONOO(-)) formation in the hippocampal CA1 region of gerbils after transient forebrain ischemia. In freely moving gerbils, NO production after 10-minute forebrain ischemia was monitored consecutively with in vivo brain microdialysis. Pretreatment with DY-9760e (50 mg/kg i.p.) significantly decreased the increased levels of NO(x)(-) (NO metabolites, NO(2)(-) plus NO(3)(-)) immediately after, 24 h after cerebral ischemia-reperfusion to the control levels of sham-operated animals. Western blot and immunohistochemical analyses using an anti-nitrotyrosine antibody as a marker of ONOO(-) formation indicated a marked increase in nitrotyrosine immunoreactivity in the pyramidal neurons of the CA1 region 2 h after reperfusion, and DY-9760e significantly inhibited increased nitrotyrosine immunoreactivity. Coincident with the inhibition of the NO production and protein tyrosine nitration, pretreatment with DY-9760e rescued the delayed neuronal death in the hippocampal CA1 region. These results suggest that the inhibitory effects of DY-9760e on the NO-ONOO(-) pathway partly account for its neuroprotective effects in cerebral ischemia.

Occipital Neuralgia As a Presenting Symptom of Cervicomedullary Dural Arteriovenous Fistula

Dural arteriovenous fistulas (DAVFs) at the cervicomedullary junction are rare and have a wide variation in presentation. We report a case of occipital neuralgia (ON) as a rare presenting symptom of cervicomedullary DAVF causing intramedullary hemorrhage at the C1 level. It is important to consider the underlying causes of ON, and precise neurological examinations and radiological evaluations are needed.

Glioblastoma with an intratumoral feeding-artery aneurysm

We report a patient with recurrent glioblastoma, in whom serial magnetic resonance angiography (MRA) demonstrated gradual enlargement of an artery feeding the tumor and the development of an intratumoral aneurysm that led to intratumoral hemorrhage. The literature contains no previous reports that clinically document intratumoral aneurysms arising from these vessels. This is a rare case of glioblastoma in which the association of an intratumoral feeding-artery aneurysm, whose rupture led to intratumoral bleeding, was documented by serial MRA imaging and follow-up.

Cerebral embolism and hormone replacement therapy

Few studies have focused on the relationship between hormone replacement therapy (HRT) for postmenopausal women or those with breast cancer and the occurrence of cerebral embolism. Results are conflicting as to whether there is a link between the two. We describe three patients who experienced cerebral embolism during HRT. A 73‐year‐old woman had a transient ischemic attack (TIA) 6 years prior to the present admission. She then took HRT oestrogen plus medroxyprogesterone acetate for about 6 years. The HRT had been prescribed by a gynaecologist for amelioration of postmenopausal symptoms. Six years after beginning HRT, she experienced sudden onset left hemiparesis due to cerebral embolism. Two other patients had been taking HRT for breast cancers. One, a 47‐year‐old woman, had taken medroxyprogesterone acetate for more than one year, for recurrence of breast cancer. She had developed sudden complete left hemiparesis due to an embolism at the carotid bifurcation. The other patient, a 72‐year‐old woman who was taking tamoxifen citrate for prevention of breast cancer relapse, experienced cerebral embolism just 2 months after beginning tamoxifen. The risk of cerebral embolism in those on HRT should be emphasized, along with the beneficial effects in terms of postmenopausal symptoms and prevention of breast cancer recurrence.

Hemisplenial- accompanied by internal border-zone infarction: clinical relevance of the splenium of the corpus callosum as a border-zone area between anterior and posterior cerebral arteries

Infarction of the corpus callosum (CC) is rare because it receives a rich supply of blood from the anterior and posterior circulation.1 We present a patient with severe haemodynamic insufficiency (HI) of the cerebral hemisphere due to steno-occlusive disease of the bilateral internal carotid arteries (ICA). His ipsilateral hemisplenial infarction of the CC enlarged progressively. We discuss the clinical relevance of the splenium of the CC as a border-zone (BZ) area between the anterior- and posterior cerebral arteries (ACA, PCA). This 63-year-old right-handed man with a medical history of hypertension and diabetes mellitus presented with dysarthria, lack of motivation and memory difficulties. MRI showed multiple acute infarcts in the internal BZ area and a single spotty infarct in the hemisplenium of the CC on the left side (figure 1A). We considered his dysarthria to be attributable to infarction of the BZ area, but we did not know whether the infarct in the CC hemispelnium was asymptomatic or played no role in his memory disturbance. Magnetic resonance- and digital subtraction angiography (MRA, DSA) revealed occlusion of the left ICA and severe stenosis of the right cervical ICA. The capacity of the left PCA was …

Stroke in Women During Long-Term Hormone Replacement Therapy Influencing Coagulation Systems

To the Editor: We read with great interest the review of Bushnell et al.1 Since 2001 we encountered 4 women who experienced cerebral infarction during long-term hormone replacement therapy (HRT).2,3 We …

Co-existence of persistent primitive trigeminal artery and another primitive carotid-basilar anastomosis associated with segmental agenesis of the ipsilateral internal carotid artery: a case report

BackgroundEmbryologically, the internal carotid artery (ICA) is comprised of seven segments, any of which may be absent. We presented a very rare case of a well-preserved persistent primitive trigeminal artery (PTA), serving as a collateral pathway to the distal internal carotid artery territory, associated with segmental agenesis of the ipsilateral internal carotid artery.ResultsA 47-year-old woman with no relevant previous medical history came to our hospital for a brain checkup. Magnetic resonance angiography revealed focal agenesis of the right ICA involving the cervical, ascending, and horizontal intrapetrous segments. The enlarged ipsilateral PTA mainly supplied the distal segments of the ICA. There was also the possibility of the co-existence of another primitive carotid-basilar anastomosis; however, we could not pursue a detailed evaluation.ConclusionsWe report a rare case of a well-preserved PTA serving as a collateral pathway to the distal ICA territory associated with segmental agenesis of the ipsilateral ICA. Clinical and radiological follow-up are needed.

Dysplastic distal basilar artery system associated with a dolicho internal carotid artery: case report.

Dysplasia of the basilar artery (BA) is a rare anatomic varint. Ontogenetically, the distal BA and proximal posterior cerebral rtery (PCA) arise from the caudal division of the embryonic interal carotid artery (ICA) [1]. We report a patient with a dysplastic istal BA and unilateral proximal PCA associatedwith an ipsilateral olicho ICA. To the best of our knowledge, this is the first docmentation of a congenital anatomic variation explicable by the evelopmental history of the distal BA and proximal PCA.