Attempt to establish an experimental animal model of moyamoya disease using immuno-embolic material--histological changes of the arterial wall resulting from immunological reaction in cats.

In this study, we investigated the relationship between intimal thickening of the internal carotid artery (ICA) and immunological reaction, and between occlusion of the ICA and development of basal collateral vessels in moyamoya disease. Rod-shaped lactic acid-glycolic acid copolymer (LGA-50) and N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide: MDP), and immuno-embolic material, were injected into cats unilaterally via the common carotid artery. Histological changes of duplication of the internal elastic lamina could be seen mainly in the terminal portion of the ICA in the animals injected with rod-shaped LGA-50 containing MDP. No angiographic changes were seen in any of the animals. These findings suggest that the immunological reaction induced by MDP caused histological changes in the intima of the ICA similar to those observed in moyamoya disease. This experimental study, however, could not clarify the development of the basal collateral vessels.</p

Experimental study of the pathogenesis of moyamoya disease: histological changes in the arterial wall caused by immunological reactions in monkeys.

Moyamoya disease is a progressive vascular disorder of unknown etiology. Theories of inflammatory and immunologic mechanisms have been proposed as the pathogeneses. We have designed a new method of administering N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) for experimental induction of moyamoya disease using an intravascular interventional technique combined with rod-shaped embolic materials made from lactic acid-glycolic acid copolymer. The embolic materials containing MDP were repeatedly injected into the right internal carotid artery of monkeys in the embolic group. Intravenous injections of MDP solution alone were performed in the intravenous group. Histological examination of the arteries demonstrated reduplication and lamination of the internal elastic laminae, which corresponded with findings of moyamoya disease in both groups. These histological changes occurred not only in the intracranial arteries on the embolization side, but also in the contralateral intracranial and even extracranial arteries. The changes were more prominent in the intravenous group than in the embolic group. We conclude that the systemic humoral factors induced by MDP in this study may be important in the pathogeneses of moyamoya disease. Our observations suggest that moyamoya disease is a systemic vascular disease and has an etiologic factor affecting both intracranial and extracranial arteries</p

Radiation damage to the normal monkey brain: experimental study induced by interstitial irradiation.

Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis.</p

Growth and rupture of unruptured cerebral aneurysms based on the intraoperative appearance.

The growth and rupture of 40 cerebral aneurysms was studied in 36 patients (14 men, 22 women; were average age, 51.8 years). Aneurysms were classified into five types according to the intraoperative findings: type 1, uniformly thin, smooth surface; type 2, thin neck and thick wall, smooth surface with or without red and/or transparent portions; type 3, uniformly thick wall, smooth surface with or without red portions; type 4, thick neck, bubbled or loculated thin wall at dome with or without red and/or transparent portions; type 5, thick wall in entirety, irregular surface with or without red portions. Five were type 1, six type 2, and 12 type 3. In four of the type 2 aneurysms, turbulence could be seen at the neck. In seven of the type 3 aneurysms, red and/or transparent portions were observed in the wall. Thirteen were type 4; nine of which had a bubbled or loculated wall with or without red and/or transparent portions. Four were type 5, with scattered red portions but a thick wall. Type 1 aneurysms were 2-5 mm, most of types 2 and 3 were 3-6 mm, type 4 were 3-13 mm, and type 5 were more than 9 mm. Types 1 and 2 had few local changes in the wall, suggesting that aneurysms at this stage are stable. Type 3 is considered to be a transitional stage to type 4 from type 2. Type 4 aneurysms had some local changes within the wall including bubbles or loculi. We concluded that aneurysms exceeding 4 mm have local pathologic changes in the wall and are critical.(ABSTRACT TRUNCATED AT 250 WORDS) </p

A new method of inducing selective brain hypothermia with saline perfusion into the subdural space: effects on transient cerebral ischemia in cats.

In this study, we tested brain surface cooling as a new method of inducing selective brain hypothermia, and evaluated its effects on focal cerebral ischemia using a cat model of transient middle cerebral artery (MCA) occlusion. Cats underwent 1 h of MCA occlusion followed by 5 h of reperfusion. Brain surface cooling was induced for 4 h during and after MCA occlusion in the hypothermia group, but not in the normothermia group. Brain surface cooling was performed using saline perfusion into the subdural space. Rectal temperature, brain surface temperature, and deep brain temperature were monitored, and regional cerebral blood flow (rCBF) and somatosensory evoked potential (SEP) were serially measured. After 5 h of reperfusion, water content was also measured. Although the rectal temperature was maintained at about 37 degrees C, the brain surface temperature decreased rapidly to 33 degrees C and was maintained at that temperature. For 3 h following reperfusion, the rCBF was lower in the hypothermia group than in the normothermia group. At 4 and 5 h after reperfusion, the recovery of SEP amplitude was significantly more enhanced in the hypothermia group than in the normothermia group. In the gray matter, the water content was significantly more diminished in the hypothermia group than in the normothermia group. These results demonstrate that our method is useful for protecting the ischemic brain from a transient MCA occlusion. This method may be adapted for neurological surgery.</p

Quantitative measurement of normal and hydrocephalic cerebrospinal fluid flow using phase contrast cine MR imaging.

&#60;P&#62;Measurements of the cerebrospinal fluid (CSF) flow using phase contrast cine magnetic resonance (MR) imaging were performed on a phantom, 12 normal subjects and 20 patients with normal pressure hydrocephalus (NPH). The phantom study demonstrated the applicability of phase contrast in quantitative measurement of the slow flow. The CSF flows of the normal subjects showed a consistent pattern with a to-and-fro movement of the flow in the anterior subarachnoid space at the C2/3 level, and they were dependent on the cardiac cycle in all subjects. However, the patients with NPH showed variable patterns of the CSF pulsatile flow and these patterns could be divided into four types according to velocity and amplitude. The amplitudes of each type were as follows: type 0 (n = 1), 87.6mm; type I (n = 2), 58.2mm (mean); type II (n = 6), 48.0 +/- 5.0mm (mean +/- SEM); and type III (n = 11), 19.9 +/- 1.8mm (mean +/- SEM). The decrease of the amplitudes correlated to a worsening of the clinical symptoms. After the shunting operation, the amplitude of to-and-fro movement of the CSF increased again in the patients with NPH who improved clinically. Some of the type III cases were reclassified type II, I and 0 and also one of the type II cases changed type I after the shunting operation. We conclude that the phase contrast cine MR imaging is a practically and clinically applicable technique for the quantitative measurement of the CSF flow.&#60;/P&#62;</p

Effect of intracarotid infusion of etoposide: modification of the permeability of the blood-brain barrier and the blood-tumor barrier in rat brain tumor model

The effect of intracarotid infusion of etoposide on the permeability of the blood-brain barrier (BBB) and brain-tumor barrier (BTB) was investigated using a model of rats injected with C6 glioma cells. Fifty four glioma-bearing rats were divided into 3 groups and treated with 0, 3, or 15 mg/kg of etoposide infused into the internal carotid artery. BBB or BTB permeability was evaluated qualitatively by the leakage of Evans blue (6 animals in each group) or quantitatively by the diffusion of carboplatin [cis-diammine (1,1-cyclobutane-dicarboxylato) platinum(II); CBDCA] (12 animals in each group) into the normal brain or the tumor tissue. BBB and BTB disruption augmented significantly in proportion to the dose of etoposide. The degree of disruption of BTB was greater than that of BBB, but the rate of disruption of BBB in proportion to increasing the dose of etoposide was higher than that in the BTB. Histopathologically, no obvious changes were observed in the animals of either the control group or the 3 mg/kg group but degenerative changes in the neurons of the hippocampus of the infused hemisphere were seen in the 15 mg/kg group. This change is thought to be caused by apoptosis because of the positive reaction with TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Our results suggest that intracarotid infusion of etoposide can increase drug delivery of concurrent antitumor agents into tumor tissue, but cerebral parenchymal cell damage is expected with a higher dosage of etoposide. Therefore, the dosage of etoposide for intracarotid infusion should be lower than 15 mg/kg in order to reduce neurotoxicity of both etoposide and concurrent anticancer drugs.</p

Combined use of cellulose acetate polymer and retrievable platinum coils for the thrombosis of cervical carotid aneurysms.

Cellulose acetate polymer (CAP) solution is a new liquid embolic material, and it has been used clinically for the thrombosis of cerebral aneurysms. The purpose of the study was to test a method of aneurysm treatment. In an experimental model, retrievable interlocking detachable coils (IDCs) were used to create an intraaneurysmal frame or prop and then CAP was injected into 20 experimentally induced canine cervical aneurysms. Intraaneurysmal thrombosis was induced 1 week after aneurysm creation. Complete thrombosis was attempted in 12 aneurysms, and partial thrombosis was attempted in 4. Four other aneurysms served as controls. Follow-up angiography was performed for up to 8 weeks, and with the exception of 4 aneurysms, which were kept for a 2-year long-term follow-up study, the aneurysms were then harvested for histological examination. Thrombosis was successfully achieved in all cases except for 2 enlarged aneurysms that were initially partially thrombosed. No thromboembolism to distal vessels was observed. No compaction or shift of the CAP-IDC complex occurred even after 2 years. Histologically, CAP and IDCs conformed to the massive thrombotic complex without any fragmentation. By creating a frame or prop with retrievable microcoils, we were able to inject the CAP implies a comparison safely and precisely than has been previously reported. Our findings suggest that this method will be useful for the treatment of cerebral aneurysms.</p