Hiroyuki Nakata

Early blood-brain barrier disruption after high-dose single-fraction irradiation in rats

SummaryWe studied the effect of high-dose single-fraction irradiation on the permeability of the blood-brain barrier (BBB) in rat brains. Immunohistochemistry with an antibody to serum albumin was used as a sensitive method for detecting the extravasation of endogenous serum components. Extravasation of albumin was detected as early as 1 day after irradiation with 20 or 40 Gy. Immunoreactivity reached its maximum after 3 days, gradually decreased during the following few weeks and had disappeared by day 30. Extravasation was much greater after irradiation with 80 Gy and continued to increase during the whole period of the experiment (6 days). Disruption of BBB this early after irradiation has not been previously documented. The time course of observed serum albumin extravasation, however, agrees well with the previous ultrastructural evidence for increased BBB permeability after irradiation with 27 Gy in monkey brains4. This transient impairment of BBB may contribute to the reversible neurological symptoms after radiosurgery. It may also allow drugs that normally not pass the BBB to do so and thus disperse in the brain when administered at this time.

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

Not only blood pressure but also behavioral activity, brain morphology, and cerebral ventricular size differ between young spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. This suggests that cerebral blood flow and cerebral metabolism may vary between these two rat strains. To test this hypothesis, we measured local cerebral glucose utilization in 31 brain areas of 26-30-week-old rats. Local cerebral blood flow was also assessed in these same areas. Cerebral glucose utilization was measured by the 2-deoxyglucose method; cerebral blood flow was determined by the iodoantipyrene method. In virtually all gray matter structures, the apparent rate of glucose utilization was lower in SHR than in normotensive WKY rats; the interstrain differences varied significantly among structures and were statistically significant (uncorrected t tests) in 14 of 28 gray matter areas. Local cerebral blood flow was fairly similar in the two rat strains. The coupling of blood flow to glucose utilization varied significantly among brain areas in normotensive WKY rats as well as in SHR. In a number of gray matter structures, the coupling of flow to metabolism differed between hypertensive and normotensive animals. These data suggest that for many brain areas, either glucose utilization or glucose partitioning differs between WKY rats and SHR.

Headache associated with postpartum cerebral angiopathy: monitoring with transcranial color-coded sonography.

We report a case of postpartum cerebral angiopathy with headache; a rare entity that affects women within the early postpartum period. Cerebral angiography revealed multiple segmental narrowings of major cerebral arteries. The patient was monitored with transcranial color‐coded sonography of the middle cerebral artery. Abnormally increased flow velocity within the middle cerebral artery decreased following initiation of steroid therapy, and the patients headache improved dramatically.

Successful Combination Chemotherapy (Cisplatinum, Vinblastine, and Bleomycin) against Peritoneal Dissemination of Intracranial Germ Cell Tumor

We found combination chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB therapy) effective in the treatment of a patient with a pineal germ cell tumor with peritoneal dissemination. The metastatic complication may have been attributable to the ventriculoperitoneal shunt tube. After the first course of PVB therapy, the disseminated tumors were decreased in size; no residual tumors were detected after the third course by laparoscopic examination, computed tomographic scanning, or echogram. Our results suggest that combined PVB therapy is effective in the treatment of extraneural metastasis from intracranial germ cell tumors.

Scalp marking for a craniotomy using a laser pointer during preoperative computed tomographic imaging: technical note.

OBJECTIVE The preoperative localization of superficial intracranial lesions is often necessary for accurate burr hole placement or craniotomy siting. It is not always easy, however, to localize the lesions over the scalp working only from computed tomographic images. We developed a simple method for such localization using a laser pointer during the preoperative computed tomographic examination. METHODS The angle of incidence, extending from a point on the scalp to the center of the computed tomographic image, is measured by the software included with the scanner. In the gantry, at the same angle as on the image, a laser is beamed from a handmade projector onto the patients scalp toward the center of the gantry. The point illuminated on the patients head corresponds to that on the image. The device and the method are described in detail herein. RESULTS We applied this technique to mark the area for the craniotomy before surgery in five patients with superficial brain tumors. At the time of surgery, it was confirmed that the tumors were circumscribed precisely. CONCLUSION The technique is easy to perform and useful in the preoperative planning for a craniotomy. In addition, the device is easily constructed and inexpensive.

Structural, Ultrastructural and Functional Correlations among Local Capillary Systems within the Brain

The cerebrovascular system supports the activities of brain cells by delivering essential substrates such as oxygen and glucose to brain tissue and removing the by-products of cerebral metabolism such as carbon dioxide and hydrogen ions. Cerebral blood vessels also carry blood-borne hormones and homoeostatic information (e.g. plasma osmolality) to the brain and distribute neurally synthesized humoral agents from brain to systemic sites.

Heterogeneous Cell Growth in Human Brain Tumors; an Analysis of the BrdU-Labeling Index and the NOR Histogram

Nucleolar organizer regions (NORs) are segments of DNA which encode ribosomal RNA (rRNA) and form loops within the nucleoli of cells [1]. Recently, many pathologists have begun to pay much attention to this region since the acidic proteins bound here can be visualized with the silver colloidal technique on histologic sections [2,3], and their increase in number seems to be related to the malignancy of tumors [1,4]. In order to study the significance of the number of silver-stained regions (AgNORs) in the evaluation of tumor malignancy, the AgNOR count per cell and the bromodeoxyuridine labeling index (BrdU LI) have been compared in human brain tumors [5,6]. These studies demonstrated a linear relationship between these two parameters in meningiomas [5] and in glial tumors [6]. On a cytological basis, however, evidence that indicates a direct connection between the increased AgNOR count and the cellular proliferative activity are not yet clear. Therefore, in the present study, we tried to re-evaluate the implications of AgNOR count in brain tumors, especially in relation to the growth activity of the cells. Special attention was paid to whether or not the AgNOR histogram may change in accordance to the regional heterogeneity of the BrdU LI, which is noted in human as well as in experimental brain tumors [7].

Radiosensitization of Human Glioma Cells by Buthionine Sulfoximine-Induced Glutathione Depletion

Depletion of intracellular glutathione (GSH) enhanced the radiosensitivity of two human glioma cell lines either under normoxic and hypoxic conditions. The enhancement ratios (ER) were 2.02 and 2.20 for hypoxic T98G and A172 cells, respectively.

The effects of chronic serum sickness on albumin distribution and glucose utilization in rat brain

SummaryThe level of cerebrospinal fluid (CSF) protein is elevated in diseases and disease models that are associated with circulating immune complexes such as serum sickness. Circulatory immune complexes are known to deposit in the basal lamina of fenestrated capillaries and may, as a result, affect both capillary bed and parenchymal function. Since the brain has both fenestrated and unfenestrated capillaries and immune complexes deposit to a varying extent in the fenestrated capillaries in chronic serum sickness, cerebral capillary permeability to protein may be altered in some brain areas and lead to the elevation of CSF proteins. In addition various other cerebrovascular and metabolic functions may also be affected by this condition. In this study either radio-iodinated serum albumin (RISA) or 2-[14C]deoxyglucose (14C-2DG) was intravenously injected into control Wistar rats and Wistar rats with chronic serum sickness; subsequently the tissue levels of radioactivity were measured by quantitative autoradiography in 4 brain areas with fenestrated capillaries and 11 brain areas with unfenestrated capillaries. The 2-min distribution of RISA, which demarcates the volume of circulating plasma in perfused microvessels and is generally proportional to local plasma flow, was the same in control and experimental rats. The passage of RISA from blood into brain over 30 min was negligible in both groups; thus cerebral capillary permeability to albumin was not detectably increased in any of these 15 brain areas by chronic serum sickness. The rate of local cerebral glucose utilization, an indicator of local metabolic and neural activity, was calculated from the 14C-2DG data and was virtually identical in control and experimental rats. These results suggest that chronic serum sickness at this stage has little effect on capillary bed permeability and parenchymal function in most, if not all, brain areas.