Shunro Endo

Independent Predictors of Late Hydrocephalus in Patients with Aneurysmal Subarachnoid Hemorrhage – Analysis by Multivariate Logistic Regression Model

Object: We determined independent variables contributing to the development of late hydrocephalus after subarachnoid hemorrhage (SAH). Methods: A total of 114 consecutive patients who underwent surgery for aneurysms within 72 h after SAH were studied. Thirty-nine patients underwent ventriculoperitoneal shunt (VPS) placement (14 patients within 30 days and 25 patients more than 30 days after onset). Univariate and multivariate analyses were performed to assess relationships among various variables and shunt placement. Results: Three variables were found to be independently associated with VPS patients: (1) the rate of SAH clearance; (2) the duration of external cerebrospinal fluid drainage, and (3) presence of neurological deficits 2 weeks after surgery, which indicates brain damage mainly caused by intraoperative manipulation and cerebral vasospasm. Conclusion: As in previous reports, intraoperative clot removal and duration of external CSF drainage were found to be closely related to the incidence of hydrocephalus. Brain damage due to intraoperative manipulation and cerebral vasospasm is seemed to be involved in the occurrence of late hydrocephalus in this study.

A method for accurate determination of stereotaxic coordinates in single-unit recording studies in monkeys by high-resolution three-dimensional magnetic resonance imaging

For single-unit recording from the brain in monkeys, the precise determination of recording targets is essential. Although magnetic resonance imaging (MRI) has been used recently in several laboratories, it has been difficult to obtain three-dimensional information on a target from two-dimensional pictures, and, therefore, it has also been difficult to determine precise coordinates. We developed a new method for precisely determining target-area coordinates based on reconstructed rendering pictures made from three-dimensional MRI data. We also combined this method with magnetic resonance angiography to avoid severe vessel complications in recording experiments.

Experimental Cerebral Vasospasm after Subarachnoid Hemorrhage

Cerebral vasospasm plays an important role in determining the prognosis of the patient, but the true nature and cause of it is still a great mystery. The course and the degree of cerebral vasospasm in cats is discussed in this report. Vasospasm of the basilar artery is induced by application of fresh blood, or blood and cerebrospinal fluid mixture incubated at 37°C for 2 to 16 days in 57 cats. In the group with fresh blood or mixtures incubated for over 15 days, the severity of induced vaso-constriction is light and the duration is short. Mixtures incubated for 5 to 10 days induced severe and prolonged vasoconstriction. The prolongation of severe vaso-constriction induced by the 7-days incubated mixture with clotted components is definitely longer than one by the mixture without clotted components. This incubation period for inducing severe vasospasm coincides with the course of vasospasm after the onset of subarachnoid hemorrhage in our clinical experience. This experimental study strongly suggests the existance of vasospasmogenic substance in the blood liberated into the subarachnoid space of the patient. It begins to act on about 3 days after subarachnoid hemorrhage, acts strongly during about 5 to 10 days, and disappears after 15 days.

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage

Abstract No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm. [Neurol Res 2001; 23: 715-720]

Experimental Cerebral Vasospasm and Sympathetic Nerve

1. Basilar artery vasospasm was induced in cats by mechanical stimulation and application of fresh arterial blood, lysed platelets in saline and blood-CSF mixture incubated at 37°C for 5 to 10 days. Following the observation of sequential changes of the caliber, the basilar arteries were fixed and extirpated, and distributions and conditions of the nerves in the vessel wall were electron-microscopically studied. 2. In the group with fresh arterial blood and lysed platelets in saline, the severity of induced vaso-constriction was light and the duration was short. Mechanical stimulation induced very short-term vaso-constriction. On the other hand, mixture incubated for 5 to 10 days induced severe and prolonged vaso-constriction. 3. In the investigation of nerve endings, small cored vesicles were transformed, decreased and disappeared gradually in the course of time after the development of vasospasm induced with mixture incubated for 5 to 10 days, but these changes were not observed in the group with fresh arterial blood, laysed platelets in saline and mechanical stimulation. 4. In the group with mixture incubated for 5 to 10 days, the relationship between the degree of vasospasm and the nerve distribution was investigated. In the portion with severe vasospasm, the nerve distribution was very rich in the most inner area of the adventitia, within 10 μ from the outer edge of the media. On the contrary, in the same area of the arterial segment with slight vasospasm the nerves were extremely scanty, and they were seen only in the more outer area of the adventitia. This relation was clear in the animals with segmental vasospasm. 5. Basilar artery vasospasm were induced by the blood-CSF mixture incubated for 7 days on the 7th days after the bilateral superior cervical ganglionectomy and perivascular sympathectomy of the cervical carotid arteries. Vasospasm was not suppressed completely but the severity of constriction was definitely lighter and the duration was shorter than the cases without sympathectomy. 6. These findings show that the nerves especially the adrenergic axon in the most inner area of the adventitia may play an important role on the genesis of late vasospasm, and this difference of the nerve distribution may participate in the individual difference in frequency or severity of vasospasm. On the other hand, function of adrenergic nerve is not so important on the genesis of early vasospasm.

Mechanism of activation of heparin cofactor II by calcium spirulan

Calcium spirulan (Ca-SP), a novel sulfated polysaccharide, increases the rate of thrombin inhibition by heparin cofactor II (HCII) more than 1000-fold through a mechanism not requiring the amino-terminal acidic domain of HCII. Activation of HCII by Ca-SP was molecular-weight dependent. Furthermore, HD22, an aptamer that binds exosite II of thrombin, produced a concentration-dependent, 15-fold reduction at 5 microM in the rate of thrombin inhibition by HCII with Ca-SP, suggesting that Ca-SP interacts with exosite II of thrombin. Mutations of Lys173 to Leu (K173L) and Arg189 to Leu (R189L) in the HCII molecule resulted in large decreases in the rate of thrombin inhibition mediated by Ca-SP and in the NaCl concentration needed for elution from Ca-SP-Toyopearl. Mutations of Lys173 to Arg (K173R) and Arg189 to Lys (R189K) showed inhibition of thrombin similar to wild-type rHCII (wt-rHCII). These results indicate that Ca-SP binds to the positive charges of Lys173 and Arg189 on the HCII molecule. In the thrombin inhibitory process by HCII, Ca-SP appears to play as a template by binding to both thrombin and HCII.

Modulation of tissue-type plasminogen activator expression by platelet activating factor in human glioma cells

AbstractPurpose. For tumor growth, proteolytic remodeling of the extracellular matrix (ECM) is a key factor. To determine proteolytic activity in human glioma cells, fibrinolytic activity, mRNA expression of fibrinolytic factors, and fibrinolytic inhibitors were studied in human glioma cell lines. The effect of platelet activating factor (PAF), a potent mediator of inflammatory and immune responses, on this fibrinolytic activity was also examined. Methods. The fibrinolytic activities of conditioned medium and cell lysates from human glioma cell lines, A172, T98G, U87 and TM1 were studied by fibrin plate zymography. mRNA expression of tissue plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors (PAI-1, PAI-2) was measured by Northern blot analysis. PAF was added to the medium, and its effects on cell proliferation, fibrinolytic activity, mRNA expression of plasminogens and inhibitors were studied. Results. mRNA expression of plasminogens and inhibitors differed between individual cell lines. Only the medium and cell lysates from A172 cells revealed fibrinolytic activity. A172 cells showed mRNA expression of tPA. PAF at low concentrations, such as 1 nM, stimulated A172 cell proliferation, and high concentrations of PAF inhibited proliferation. PAF stimulated tPA release into the conditioned medium. mRNA expression of tPA was stimulated by low concentrations of PAF and inhibited by high concentrations. Conclusion. The variability of mRNA expression of plasminogen activators (PAs) between different glioma cell lines may indicate that plasminogens and their inhibitors do not directly correlate with brain tumor growth. PAF may be an important factor in the local control of fibrinolytic activity in glioma and its proliferation.

Vasoconstriction of external carotid arteries after rupture of intracranial aneurysms

SummaryVasoconstriction of the external carotid arteries, which has not been previously reported, was investigated angiographically in 23 patients who had intracranial vasospasm after aneurysm rupture. In about 50% of these patients vasoconstrictive change in the external carotid arteries was also found. These changes were not seen in control cases without intracranial vasospasm. Pathogenesis of the vasoconstriction of the external carotid arteries was discussed with particular emphasis on the relationship with sympathetic nerves.