Three-dimensional analysis of vasospastic major cerebral arteries in rats with the corrosion cast technique.

BACKGROUND AND PURPOSE: Although mice, rats, and other small animals are commonly used for molecular biology research, their use in the evaluation of cerebral vasospasm after subarachnoid hemorrhage is somewhat problematic because of the correspondingly small size of their cerebral vessels. We have already reported that the corrosion cast technique was useful for evaluating newly formed cerebral vessels in neural grafts in these small animals. In the present study we applied the corrosion cast technique to the evaluation of hemolysate-induced cerebral vasospasm in rats and performed three-dimensional analysis for comparison. The casting was done 10 minutes after the hemolysate injection, so that only acute "vasospasm" was assessed. METHODS: After withdrawal of 0.1 mL cerebrospinal fluid, 0.2 mL hemolysate (n = 9) or saline (n = 10) was injected into the cisterna magna of male Sprague-Dawley rats weighing between 300 and 350 g. Ten minutes later, perfusion of a semipolymerized casting medium was performed at an injection pressure of 100 to 120 mm Hg. The brains were immersed and corroded in 10% NaOH solution. After these procedures, the basilar artery as well as peripheral vessels was analyzed morphologically with scanning electron microscopy. Conventional histological analysis with the use of paraffin-embedded section with hematoxylin-eosin staining was also performed, and the results were compared with those for the corrosion cast methods. RESULTS: In the saline-injected group, SEM showed that the inner surface of the basilar artery was smooth and the form of the endothelial cell was printed on the surface of the cast. In the hemolysate-injected group, the basilar artery showed an apparent vasospasm over its entire length, and corrugation was observed on the inner surface of the basilar artery in a three-dimensional fashion. Higher magnification revealed that the nuclei of the endothelial cells were distorted. Local narrowing of the basilar artery and vasospasm in the arteries of the anterior circulation and in peripheral arteries were also observed. Measurement of the inner diameter of the basilar artery showed 37.8% contraction in the hemolysate-injected group compared with the saline-injected group by the corrosion cast method. This degree of vasospasm was similar to that observed by the conventional histological method. CONCLUSIONS: In this report we show that detailed three-dimensional observation in the rat can be performed qualitatively and quantitatively with the corrosion cast technique. We conclude that this method derives an accurate measurement of the diameter of rat major cerebral arteries and is more reliable for analyzing vasospasm in rats than angiography and other conventional procedures.

Surgical treatment of transitional internal carotid aneurysms.

Ten transitional internal carotid aneurysms are presented. Necks and domes of these aneurysms were located in both the intradural subarachnoid and extradural intracavernous spaces across the carotid dural ring. Seven aneurysms were small, 2 were large, and 1 was giant. Two patients had subarachnoid haemorrhage (SAH), 2 compressive symptoms, 5 SAH from rupture of associated lesions (aneurysms or AVM) and 1 case was an incidental finding. Direct clipping was performed successfully in all patients. The overall surgical outcome was excellent in all patients, with transient complications in 4 cases. It is suggested these aneurysms should be treated with direct clipping whether ruptured or not because of the risk of SAH. A classification of paraclinoidal region aneurysms including cavernous sinus aneurysms extending into the intradural subarachnoid space is proposed.

Meningiomas arising from the falcotentorial junction. Clinical features, neuroimaging studies, and surgical treatment.

Meningiomas arising from the falcotentorial junction are extremely rare. The authors describe the clinical features, neuroimaging studies, and results of surgical treatment of meningiomas of the falcotentorial junction and clarify the characteristics of this lesion based on a review of the literature and seven patients treated at their institution. The most common symptoms resulted from intracranial hypertension. Upward-gaze palsy appeared in only one patient. Computerized tomography (CT) showed no specific findings, but there was no evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a round, smooth-bordered mass with a peritumoral rim, without edema, and showing marked contrast enhancement. The multiplanar capability of MR imaging delineated the relationship between the tumor and adjacent structures better than did CT. Detailed knowledge of the vascular structures, especially evidence of occlusion of the galenic venous system and the development of collateral venous channels, is critical for successful surgery; stereoscopic cerebral angiography is necessary to achieve this aim. The seven patients described developed five types of collateral venous channels: through the basal vein of Rosenthal to the petrosal vein, through the veins on the medial surface of the parietal and occipital lobes to the superior sagittal sinus, through superficial anastomotic veins, through veins of the posterior fossa to the transverse or straight sinus, and through the falcian veins to the superior sagittal sinus. The first three types mainly developed after occlusion of the galenic system. The tumors were removed through the occipital transtentorial approach with a large window at the posterior part of the falx. A favorable prognosis for patients undergoing surgical treatment of falcotentorial junction meningiomas can be expected if detailed neuroimaging studies and microsurgical techniques are used.

[Collateral venous channels in occlusion of deep cerebral veins and sinuses].

The authors report on the relationship between occlusion or stenosis of the deep cerebral veins and sinuses and the development of collateral venous channels in pineal region tumors. Five cases of meningioma arising from the falcotentorial junction were the subject of this study. There were two males and three females with an average age of 51.2 years (range: 26-67). The straight sinus (SS) and posterior part of the great vein of Galen (GVG) were included in the occlusion or stenosis of the deep cerebral veins and sinuses in 3 cases, the GVG, SS and posterior part of the internal cerebral vein in 1, and the SS alone in 1. The various types of collateral venous channels following the occlusion could be classified a type 1, from the basal vein of Rosenthal (BVR) to the petrosal vein via the lateral mesencephalic and/or anterior pontomesencephalic veins; type 2, via the veins on the medial surface of the parietal and/or occipital lobe to the superior sagittal sinus (SSS); type 3, dilated superficial anastomotic veins; type 4, via the posterior fossa venous circulation to the transverse sinus or the SS; and type 5, via the falcian veins to the SSS. The first three types of collateral venous channels seem to be important following occlusion or stenosis of deep cerebral veins and sinuses. Stereoscopic angiograms are essential to analyze deep venous channels around deep-seated tumors. Clear identification of occlusion or stenosis and the development of venous system collaterals on angiograms is important to the surgical treatment of pineal region tumors.

Magnetic resonance characteristics of meningiomas arising from the falcotentorial junction.

We report the magnetic resonance features of meningiomas at the falcotentorial junction in six patients. Three tumors showed several characteristics on magnetic resonance images. They demonstrated hypo- or isointensity on T1-weighted images and iso- or hyperintensity on T2-weighted images. The degree of contrast between tumor and brain parenchyma, however, was less marked. The tumors often had a mottled appearance on T2-weighted images owing to their hypervascularity. All of the tumors had a peritumoral rim, and no edema was seen in adjacent brain parenchyma. With the injection of gadolinium, the tumors in all patients markedly enhanced; the adjacent dura was enhanced in four patients.

Trigeminal neurinoma presenting with intratumoral hemorrhage: report of two cases.

We report 2 cases of trigeminal neurinoma presenting with spontaneous intratumoral hemorrhage. There are only 2 similar cases reported in the literature. Presenting symptoms were headache, diplopia, disturbed consciousness and trigeminal disturbance with sudden onset. CT scan showed a typical fluid-fluid level within low-density mass in the cerebellopontine angle in one case. On MRI, one case showed a typical fluid-fluid level on T2-weighted image and another one had mixed signal intensities including hyper- and hypointensities on both T1- and T2-weighted images. Histologically, increased vascularity, consisting of dilated and thin-walled vessels presenting telangiectatic or cavernous angiomatous appearances were observed in the specimens in both cases. The size of these tumors was about 3 cm each in diameter. Risk factors for hemorrhage appear to be large tumor size and increased vascularity.

Subarachnoid haemorrhage produces differential effects on transmitter kinetics at cerebral periarterial noradrenergic terminals.

The functional states of cerebral perivascular noradrenergic terminals were investigated following experimental 'closed-space' subarachnoid haemorrhage (SAH) in cat. The left middle cerebral artery (L-MCA) was compared to the ruptured right (R-MCA) one. Permeability kinetics of 3H-NA (noradrenaline) were measured simultaneously in isolated segments of paired R- and L-MCAs, testing responses to electrical field stimulation and the presence of the alpha-adrenoceptor antagonist, phentolamine, at different concentrations and times post-SAH. Fractional 3H-NA efflux from ruptured R-MCAs was reduced to undetectable levels at 18 h to at least 3 d post-SAH. Response to electrical stimulation partially recovered at 10 d and approached the controls by 16 to 30 d. In the L-MCAs, 3H-NA efflux was decreased up to 90% at 18 h, but recovered to control level by 3 d, unless it too became involved by encroachment of blood from the SAH side. The fractional 3H-NA efflux in the controls was typically augmented by phentolamine, reaching a peak at 0.3 microM of the drug. This overflow response was completely lost between 0.03 and 3.0 microM phentolamine in the R-MCAs for at least 30 d post-SAH, whereas uninvolved L-MCAs regained drug-induced overflow at 10 to 16 d post-SAH. Uptake of 3H-NA after SAH was also decreased 30 to 50% for both MCAs at 18 h and 3 d post-SAH. Control 3H-NA uptake was regained by 10 d post-SAH in the L-MCA but not until 16 d in the R-MCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal enkephalin and catecholamine contents following subarachnoid hemorrhage in cats.

A "closed space" subarachnoid hemorrhage (SAH) was produced experimentally in cats by rupture of the right middle cerebral artery to test the working hypothesis that a stressful event which provokes powerful sympathoadrenal discharge: causes a massive release of co-stored endogenous enkephalins together with catecholamines, induces an increased rate of opioid peptide precursor processing and/or synthesis, and eventually results in markedly elevated tissue levels of enkephalins relative to controls and to co-stored catecholamines. Adrenal medulla and other tissues were analyzed for met- and leu-enkephalins by RIAs and norepinephrine and epinephrine by HPLC-EC at 4 hrs, 3, 10, 16 and 30 days post-SAH. Catecholamines of adrenal medulla were already decreased at 4 hrs and by 3 days post-SAH depletion of epinephrine reached 86% and norepinephrine 53% compared to controls. Concurrently, at 4 hrs and 3 days post-SAH, the adrenal medulla was depleted 47% of met- and 53% of leu-enkephalins. By 10 days post-SAH, when catecholamines had regained control levels, met-enkephalin was elevated to 240% of control and 435% compared to the 3 day depletion; it remained elevated through 30 days post-SAH. In comparison, after 10 days reserpine treatment when catecholamines were markedly depleted, met-enkephalin rose to 970% and leu-enkephalin to 360% relative to controls, confirming recent reports in the literature. The data suggest that release of enkephalins originates primarily from epinephrine-type cells of the adrenal medulla in cat.

Heparin reduces proliferative angiopathy following subarachnoid hemorrhage in cats.

Subarachnoid hemorrhage (SAH) was produced in cats by transorbital rupture of the right middle cerebral artery (MCA). In untreated cats, widespread proliferative angiopathy occurred in both MCA's by 16 days after SAH. In cats that received systemic heparin, the pathological events following SAH were clearly reduced in the ruptured artery, and were not present in the contralateral left MCA. Platelets are known to adhere to the subintimal surface of cerebral arteries after SAH. The authors suggest that platelet-derived growth factor released from the intimal platelet carpet following SAH may be the stimulus for the development of proliferative angiopathy, and that this platelet factor is inhibited by heparin.

Arterial wall changes in early human vasospasm.

Histological, histochemical, and histoimmunological studies were conducted on cerebral arteries from three living patients with a recent subarachnoid hemorrhage. There seemed to be a correlation between the severity of vasospasm and the magnitude of pathological alterations. Myofibroblasts and Type V collagen within the medial layer were abundant in vessels showing marked constriction, but were less conspicuous in those arteries showing milder involvement. Intracranial arteries from patients who died from noncerebral causes did not demonstrate these changes. Thus, myofibroblasts and Type V collagen may be related to cerebral vasospasm by holding the damaged vessel in a contracted phase for weeks during the healing period.

Prostacyclin and thromboxane in cerebral vasospasm II: Effects of thromboxane synthetase inhibitor (OKY-1581) on experimentally-induced cerebral vasospasm.

OKY-1581, a thromboxane A2 (TXA2) synthetase inhibitor, was administered to cats with normal and constricted basilar arteries. At a dose of 60mg/kg (i.v.), both normal and constricted vessels dilated, and the mean arterial blood pressure (MABP) fell from 55 to 75 mmHg. If MABP remained constant, vessel diameter did not change. Subarachnoid hemorrhage (SAH) was simulated by intracisternal injection of autologous arterial blood. Regional cerebral blood flow (rCBF) was assessed by the heat clearance and H2 clearance methods. The two methods presented similar response profiles. rCBF responses to intravenous OKY-1581 fell into 3 categories: A) no change in rCBF, B) decrease in rCBF related to MABP and C) increase in rCBF in the presence of hypotension. Types A and B were observed in 3 out of 10 control cats and 4 out of 14 SAH-induced cats, with Type C responses in the remainder. There was no significant difference between the groups. While the results do not support a major role for TXA2 in cerebral vasospasm pathogenesis, OKY-1581 may still be useful in the treatment of cerebral vasospasm, as it improves distal and deep circulation and inhibits platelet aggregation.

Prostacyclin and thromboxane in cerebral vasospasm: effects of prostacyclin on experimentally-induced cerebral vasospasm.

The basilar artery was exposed transclivally , and a vascular spasm was produced by topical application of a lysed erythrocyte solution. The maximum fall in the mean arterial blood pressure (MABP) after administering of 2 micrograms/ kgBW and 15 micrograms/ kgBW of PGI2, ranged from 35 to 45 mmHg and from 65 to 85 mmHg, respectively. The drop in MABP after an injection of papaverine hydrochloride (1.5 mg/ kgBW ) was between 30 and 40 mmHg. If MABP did not fall, the vessel diameter did not change. Although papaverine elicited marked dilation of both normal and spastic basilar arteries, PGI2 did not dilate normal basilar arteries and produced only a slight dilation of spastic basilar arteries. Subarachnoid hemorrhage (SAH) was simulated by an intracisternal injection of fresh autologous arterial blood 3 days prior to experimentation. Changes in regional cerebral blood flow (rCBF) were measured by the heat clearance method, before and after an intravenous administration of either PGI2 or papaverine hydrochloride. Changes in rCBF fell into 3 categories: Type A, no change; Type B, a change which varied with the arterial blood pressure, and Type C, an increase rCBF despite systemic hypotension. Type A or B was observed in 17 out of 19 cats with SAH in which PGI2 was administered intravenously, and Type C was observed in only 2 cats. Thirteen untreated control cats produced a Type A or B response in 12, and Type C response in only one cat. There were no significant differences between the control and SAH groups. When 15-hydroperoxy-5, 8, 11, 13-eicosatetraenoic acid (15-HPETE) was infused, the same results prevailed. Papaverine hydrochloride increased rCBF either transiently or continuously in all cats. These results suggest that PGI2 dilates extracranial rather than intracranial vessels regardless of the presence or absence of cerebral vasospasm.