The protective effect of experimental subarachnoid haemorrhage on sodium dehydrocholate-induced blood-brain barrier disruption

Summary The potential interactive effects between subarachnoid hemorrhage (SAH) and blood brain barrier (BBB) disruption were studied in a rat model. Experimental subarachnoid hemorrhage was produced in twenty rats (experimental group) by the intracisternal injection of blood. In ten additional rats (control group), saline was administered in place of blood. Analysis of mean blood pressure (MBP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP) demonstrated an increase in ICP and MBP and a drop in CPP in all animals following intracisternal injection. Subsequent infusion of the left internal carotid artery with sodium dehydrocholate resulted in blood-brain barrier (BBB) disruption in both groups as evidenced by Evans blue staining of the infused cortex. The extent of BBB disruption was significantly greater in the control group than the experimental group.Analysis of the experimental group demonstrated that animals with the lowest pre-SAH MBP and the lowest CPP during the maximum blood pressure response to SAH demonstrated the greatest resistance to experimental BBB disruption.The possibility of ischemia as a contributing factor in BBB protection subsequent to SAH is discussed.     

Barrier disruption in the major cerebral arteries following experimental subarachnoid hemorrhage

The effects of experimental subarachnoid hemorrhage (SAH) on the blood-arterial wall barrier in the major cerebral arteries were studied in 20 normotensive dogs. Horseradish peroxidase (HRP) was given intravenously before the animals were sacrificed to assess the integrity of the barrier. Transient elevation of intracranial pressure (ICP) produced by cisternal injection of saline solution resulted in HRP leakage at the branching points of the major cerebral arteries. Extensive disturbance of the blood-arterial wall barrier was consistently observed in the major cerebral arteries after SAH, with or without elevation of ICP. These results suggest that both subarachnoid clot and a sudden rise in the ICP are important factors causing the breakdown of the blood-arterial wall barrier, but that the effect of the clot is the most profound. Electron microscopy revealed that opening of the interendothelial junctions is one of the important mechanisms responsible for the HRP leakage in the major cerebral arteries following SAH. Disturbance of arterial permeability in the major cerebral arteries following SAH probably accounts for the abnormal post-contrast enhancement that occurs in patients who are prone to develop vasospasm following aneurysm rupture, and is probably involved in the pathogenesis of vasospasm.     

Barrier disruption in the major cerebral arteries after experimental subarachnoid hemorrhage in spontaneously hypertensive and normotensive rats

The effects of experimental subarachnoid hemorrhage (SAH) on the blood-arterial wall barrier in the major cerebral arteries were studied in 24 spontaneously hypertensive rats (SHR) and 13 Sprague-Dawley rats (SDR). Horseradish peroxidase (HRP) was given intravenously before killing the animals to assess the integrity of the barrier. In the acute experimental group, transient elevation of intracranial pressure (ICP) and systemic arterial pressure produced by cisternal injection of whole blood, saline solution, or Elliott's B solution resulted in extensive disturbance of the blood-arterial wall barrier. In the chronic group, only the cisternal injection of whole blood in SHR brought about an extensive and marked disturbance of the arterial permeability. These results suggest that: (a) early breakdown of the blood-arterial wall barrier seems to be due to a sudden rise in the ICP or arterial pressure; (b) in the chronic experiments, the subarachnoid clot is the most important factor responsible for the permeability changes; and (c) in the chronic SAH experiments, the blood-arterial wall barrier seems to be more vulnerable in SHR than in Sprague-Dawley rats. Due to the well-known similarities between SHRs and hypertensive human beings, patients with chronic hypertension should be considered at high risk after SAH for extensive blood-arterial wall barrier disturbances.     

Subarachnoid and intracerebral hemorrhage associated with necrotizing angiitis due to methamphetamine abuse--an autopsy case.

The authors report an autopsy case of methamphetamine-related intracranial hemorrhage and vasculitis. A 22-year-old female was comatose after an intravenous injection of an unknown dose of methamphetamine. Computed tomographic scans demonstrated massive subarachnoid hemorrhage and hematoma in the corpus callosum. Cerebral angiography revealed nonfilling of bilateral intracranial carotid arteries and extravasation of contrast medium from the right pericallosal artery which was visualized retrogradely via the vertebral artery. Postmortem studies found cerebral edema, subarachnoid, intraventricular, and intracerebral hemorrhage, and intracranial vasculitis, but no aneurysm or arteriovenous malformation. Necrosis of vessel walls with destruction of the smooth muscle layer, but no leukocytotic infiltration of the vessel walls were observed in all major cerebral arteries. The hemorrhage probably resulted from medial necrosis in the large intracerebral vessels, and a sudden drug-induced rise in blood pressure.     

Vitreous hemorrhage as a complication of subarachnoid hemorrhage (Terson's syndrome) (author's transl)

We represent a case of vitreous hemorrhage due to subarachnoid hemorrhage from a ruptured aneurysm of the right vertebral artery to draw attention to this complication. A 53-year-old man was admitted to our hospital because of generalized headache and reduced visual acuity of both eyes. On admission the patient was alert and there were moderate nuchal stiffness and mild symmetrical hyperreflexia in the extremities. Ophthalmological consultation revealed bilateral retinal, subhyaloid and vitreous hemorrhages. Four-vessel angiography demonstrated an aneurysm of the right vertebral artery. At operation, it became clear that the aneurysm was a dissecting one. The vertebral artery was clipped at the most proximal intracranial portion. Postoperative course was smooth and uneventful except deteriorated visual acuity. His visual acuity deteriorated continuously to hand movements 18 days after subarachnoid hemorrhage. His visual acuity, however, gradually improved without specific treatment. At the time of this writing, his visual acuity is 1.0 on both sides. Vitreous hemorrhage is a rare complication following a reptured aneurysm. Pertinent literature concerning fundal hemorrhage, especially vitreous hemorrhage, associated with subarachnoid hemorrhage suggests that it may occur as a result of sudden increase of intracranial pressure.     

Evidence for direct impairment of neuronal function by subarachnoid metabolites following SAH

Dysfunction of neuronal signal processing and transmission occurs after subarachnoid hemorrhage (SAH) and contributes to the high morbidity and mortality of this pathology. The underlying mechanisms include early brain injury due to elevation of the intracranial pressure, disruption of the blood–brain barrier, brain edema, reduction of cerebral blood flow, and neuronal cell death. Direct influence of subarachnoid blood metabolites on neuronal signaling should be considered. After SAH, some metabolites were shown to directly induce disruption of neuronal integrity and neuronal signaling, whereas the effects of other metabolites on neurotoxicity and neuronal signaling have not yet been investigated. Therefore, this mini-review will discuss recent evidence for a direct influence of subarachnoid blood and its metabolites on neuronal function.     

Influence of the type and rate of subarachnoid fluid infusion on lethal neurogenic pulmonary edema in rats

In patients who experience sudden death from spontaneous subarachnoid hemorrhage, more than 90% present with acute pulmonary edema. The underlying pathogenesis of this complication is poorly understood. In addition, the specific role of the extravasated blood products and the associated elevation in intracranial pressure leading to the systemic and pulmonary effects during subarachnoid hemorrhage are not well established. The authors tested a new model of acute and severe subarachnoid hemorrhage comparing fresh whole autologous blood (n = 20) with 5% albumin (n = 19) injected at two different rates (35 seconds versus 24 minutes) into the cisterna magna of anesthetized, mechanically ventilated rats. Cerebral and systemic hemodynamics and the corresponding pulmonary function were evaluated. The type of fluid injected had no influence on survival or hemodynamic and respiratory parameters. Rapid infusion of either blood or albumin (n = 14) produced an acute and transient rise in intracranial pressure (37.9 +/- 3.5 mm Hg) associated with systemic hypertension and increased cerebral perfusion pressure that was sustained in survivors but not in nonsurvivors. Slow infusion (n = 23) produced a more progressive increase in intracranial pressure to 31.2 +/- 7.1 mm Hg with a parallel and sustained increase of systemic blood pressure and preserved cerebral perfusion pressure in survivors, but produced a pattern of more severe hypertension followed by hypotension in nonsurvivors. Sixty-four percent of animals (rapid infusion) and 48% of animals (slow infusion) survived the challenge and presented no pulmonary alterations. In contrast, nonsurviving rats developed reduced lung compliance and gas exchange, an increased alveolar-arterial protein concentration ratio (0.36 +/- 0.02 versus 0.17 +/- 0.03 in survivors; P <.0001), and increased lung weight (5.7 +/- 0.3 g versus 2.0 +/- 0.1 g; P <.0001), demonstrating a fulminant increased permeability pulmonary edema, leading to death within one hour. These results indicate that the chosen rapid- and slow-injection rates resulted in a similar death rate of 50%. Mortality was similar for blood and albumin administration, pulmonary edema occurred in nonsurvivors in both the rapid- and slow-injection groups, and pulmonary edema is associated with more severe hypertension in the slow-injection group. Furthermore, these results suggest that the development of neurogenic pulmonary edema that is characterized by an acutely increased capillary permeability to proteins is independent of the degree of intracranial pressure increase or the type of fluid administrated.     

Haemodynamic,intracranial pressure and electrocardiographic changes following subarachnoid haemorrhage in rats

Summary Experimental induction of subarachnoid haemorrhage in rats resulted in acute haemodynamic changes. Heart rate decreased concomitantly with a rise in arterial blood pressure. Intracranial pressure increased and consequently cerebral perfusion pressure dropped. These changes as well as the observed electrocardiographic (ECG) changes were comparable to those reported in patients. Apart from blood also saline, when introduced into the cisterna magna, was able to elicit such abnormalities. The haemodynamic and electrocardiographic changes, which result from subarachnoid haemorrhage, may even become aggravated, when repetitive injections of blood or saline are given into the cisterna magna and when cerebral angiography is performed prior to induction of the subarachnoid haemorrhage. Chronic intracranial pressure monitoring during the 48 hours following subarachnoid haemorrhage revealed no significant rise in pressure.A thorough control of the experimental conditions is thus of utmost importance in order to give a valid interpretation of the observed anomalies.     

Pituitary apoplexy with an unruptured carotid-ophthalmic aneurysm

The association of pituitary adenoma and adjacent cerebral aneurysm is not uncommon and acute hemorrhage into a pituitary adenoma is also a well recognized condition. However, the simultaneous occurrence of pituitary apoplexy with intracranial aneurysm is very rare. Such a case demonstrates the diagnostic difficulty in distinguishing between pituitary apoplexy and rupture of an aneurysm. We reported a patient with subarachnoid hemorrhage in whom a hemorrhage into the pituitary adenoma and a carotid-ophthalmic aneurysm was proven, and discussed the differential diagnosis and treatment. A 41-year-old man, who developed sudden severe headache with nausea and vomiting, was admitted to our hospital. Examination disclosed a mildly stuporous man with bilateral defects of upper lateral visual fields and lumbar puncture revealed subarachnoid hemorrhage. Plain radiographs of the skull showed an enlarged and eroded sella turcica. Carotid angiography revealed a left carotid-ophthalmic aneurysm. A plain CT scan demonstrated an acute suprasellar hematoma. A transsphenoidal operation was performed and postoperative course was uneventful.     

Acute changes in the dynamics of the cerebrospinal fluid system during experimental subarachnoid hemorrhage

Early changes in intracranial pressure (ICP), ICP volume index, and resistance to absorption of cerebrospinal fluid induced by experimental subarachnoid hemorrhage were studied in cats. After SAH, the ICP was slightly elevated, and there was a decrease in the buffering capacity of the intracranial space and a sharp rise in outflow resistance. During infusion of blood into the cisterna magna with a constant infusion rate, an extensive increase in ICP could be demonstrated in contrast to the infusion of saline, which caused only slight elevation of ICP. Furthermore, during blood infusion, the ICP level did not reach a plateau phase of pressure, as was demonstrated during infusion of saline. It is suggested that the marked increase in ICP during blood infusion into the subarachnoid space is caused by intracranial volume loading and the simultaneous increase in cerebrospinal fluid outflow resistance. It is concluded that the reported relationship between increased cerebrospinal fluid outflow resistance and increased ICP supports the hypothesis of a strong increase in ICP during subarachnoid hemorrhage in human subjects.     

Subarachnoid hemorrhage caused by a ruptured anterior spinal artery aneurysm

A 51-year-old man presented with an extremely rare case of intracranial subarachnoid hemorrhage caused by rupture of an anterior spinal artery aneurysm manifesting as disturbance of consciousness following sudden onset of neck pain and numbness of the extremities. Cranial computed tomography revealed subarachnoid hemorrhage, mainly in the posterior fossa. Cerebral angiography studies on admission and on the 4th day demonstrated no definite abnormality as a bleeding source. A ventricular catheter was inserted to treat the acute hydrocephalus, and conservative management was continued during the acute period. Third angiography on the 18th day demonstrated an anterior spinal artery aneurysm at the C1 level which was considered to be the bleeding site. After conservative treatment, the patient was discharged without neurological deficits. Fourth angiography on the 108 th day disclosed spontaneous disappearance of the aneurysm, which was confirmed by the fifth angiography on the 269 th day. If subarachnoid hemorrhage of unknown etiology is encountered, spinal artery aneurysm should be considered as the bleeding source. Despite the controversy concerning the treatment strategy, ruptured spinal artery aneurysms can be treated conservatively because of the possibility of spontaneous regression. Follow-up angiography is required to evaluate the natural course of the lesion.     

Blood-brain barrier damage during the acute stage of subarachnoid hemorrhage, as exemplified by a new animal model

Models have been devised and characterized in the laboratory rat for studying the neuropathology of subarachnoid hemorrhage. Several ways of injecting blood via different routes have been tried; cortical subarachnoid administration is the most reproducible suitable model. The location of injected blood was detected in histological sections. In this rat model for subarachnoid hemorrhage, the arterial blood pressure and the intracranial pressure did not elevate significantly, and the influence of major ischemic components in the development of brain edema could also be ruled out. Measurements performed on the water, electrolyte, and albumin contents of brain tissue have clearly indicated that the brain edema developing in the acute stage of rat experimental subarachnoid hemorrhage could be classified as having a primarily vasogenic component as well. These findings may have implications in the treatment of subarachnoid hemorrhage.     

Cerebellar hemorrhage after coil embolization for a ruptured vertebral dissecting aneurysm

BACKGROUND: We present a case of ruptured vertebral dissecting aneurysm that exhibited cerebellar hemorrhage after successful embolization of the vertebral artery including the dissected site. CASE PRESENTATION: A 59-year-old man suffered a sudden onset of severe occipital headache when he looked up. Computed tomography demonstrated subarachnoid hemorrhage. Angiography revealed a right vertebral dissecting aneurysm distal to the posterior inferior cerebellar artery. Endovascular embolization of the aneurysm was performed with preservation of the posterior inferior cerebellar artery. The next day, the patient suffered a cerebellar hemorrhage in the vermis. The intracranial pressure was controlled by external ventricular drainage. The patient was discharged with mild cerebellar ataxia and bilateral abducens nerve palsy. CONCLUSION: In a case of vertebral dissecting aneurysm distal to the posterior inferior cerebellar artery, blood circulation in the vertebral arterial system may change after embolization of the aneurysm. In our case, the preserved posterior inferior cerebellar artery might have been hemodynamically stressed postoperatively, resulting in cerebellar hemorrhage. Therefore, strict control of blood pressure is essential in the acute stage after occlusion of the aneurysm.     

CT三维血管造影诊断出血动脉瘤

目的 评价CT血管造影(CTA)在颅内动脉瘤破裂后蛛网膜下腔出血诊断中的价值及手术指导意义。方法 对63例急性蛛网膜下腔出血病人急诊行螺旋CT扫描,然后行脑血管三维成像。结果 发现颅内动脉瘤24例。有1例阴性经全脑血管造影(DSA)发现存在动脉瘤。诊断均以手术证实。结论 CTA对动脉瘤蛛网膜下腔出血是一种微创、快速、准确的诊断技术,对于急诊或危重病人应为首选。     

The effects of local intraparenchymal pentobarbital on intracranial hypertension following experimental subarachnoid hemorrhage

Barbiturates are often utilized clinically in circumstances in which elevated intracranial pressure is expected. In this study, the mechanism of action of barbiturates was examined in dogs with intracranial hypertension induced by injecting autogenous incubated blood into the chiasmatic cistern. Intracranial pressure and systemic blood pressure were continuously monitored. A single bilateral administration of powdered pentobarbital (2 mg and 0.4 mg) in experimental animals and solid d-glucose (2 mg) in control animals was given into the posterior hypothalamus, pontine reticular formation, or medullary reticular formation when intracranial pressure reached 20-30 mmHg after the blood injection--usually in 3-6 h. The increased intracranial pressure following the experimental subarachnoid hemorrhage was always associated with either intracranial pressure irregularities or concomitant blood pressure variations, suggesting the presence of vasomotor instability. Administration of both 2 mg and 0.4 mg of pentobarbital into the medulla caused a significant (P less than 0.01) decrease of the intracranial pressure to 44 and 65% of control and stabilization of the intracranial pressure irregularities, whereas pentobarbital given at the other sites did not. The blood pressure was also decreased significantly (P less than 0.01) to 80 and 88% of control and the blood pressure variations were stabilized in animals after administration of pentobarbital into the medulla, whereas in those given pentobarbital at the other sites, it was not. The results suggest that, in the presence of elevated intracranial pressure following experimental subarachnoid hemorrhage, the mechanisms of action of barbiturates in reducing the intracranial pressure may result from alleviation of cerebral vasomotor instability by depression of the vasomotor center of the medulla.     

Hydrocortisone for the treatment of cerebral vasopasm--(1) experiments in dogs (author's transl)

The usefulness of hydrocortisone for the treatment of cerebral vasospasm was investigated using dogs by measuring changes in cerebral arterial diameter in angiograms as well as in other parameters such as blood pressure, intracranial pressure and CBF. The intrathecal (50-300 mg) or intravenous (100 mg/kg) injection of hydrocortisone resulted in a marked dilatation of cerebral arteries both in control animals and vasospastic animals after subarachnoid hemorrhage. The intrathecal injection caused a temporary rise in blood pressure immediately following the injection. Cerebrospinal fluid pressure was increased progressively. On the other hand, the intravenous injection resulted in a fall in blood pressure and a transient rise in cerebrospinal fluid pressure. CBF showed a tendency to increase both with intrathecal and intravenous injection. With intravenous injection a high CSF level of cortisol was found 1 and 2 hours after the injection and it was correlated to the degree of cerebral arterial dilatation, indicating that a significant amount of hydrocortisone could penetrate into the CSF and dilate the intracranial vessels by its direct pharmacological action.     

Ruptured intracranial aneurysm associated with unruptured abdominal aortic aneurysm--case report

A 61-year-old male with hypertension presented with sudden onset of headache and nausea due to subarachnoid hemorrhage (SAH). He had two siblings with history of SAH due to ruptured intracranial aneurysms. Right carotid angiography on admission showed an anterior communicating artery aneurysm. At that time, the extracranial arteries were not examined. The aneurysm was clipped with no complications. A pulsating mass was palpable in the abdomen 37 days after the onset. Ultrasonography and computed tomography showed an abdominal aortic aneurysm with intraluminal thrombus, measuring 8 x 9 x 8 cm. Normal pressure hydrocephalus had already developed. The patient underwent elective abdominal aortic aneurysm resection before ventriculoperitoneal shunting. After shunting, he recovered fully. The present case indicates that unpredictable sudden enlargement of associated abdominal aortic aneurysm is possible in patients with ruptured intracranial aneurysms.     

A case of a persistent primitive proatlantal intersegmental artery with a ruptured basilar bifurcation aneurysm

A case of persistent primitive proatlantal intersegmental artery (PPPIA) associated with a ruptured basilar bifurcation aneurysm was reported. A 44-year-old male with sudden headache was admitted to our hospital. CT scan revealed subarachnoid hemorrhage. Cerebral angiography revealed anomalous anastomosis between the internal carotid artery and the vertebral artery at the proatlantal region. This anastomosis branched off from the left internal carotid artery at the C4 level and joined the horizontal portion of the left vertebral artery. It was thought to be PPPIA. Angiography also revealed an aneurysm of the basilar bifurcation which was responsible for the patient's subarachnoid hemorrhage. The aneurysm was successfully treated by endovascular embolization with Guglielmi detachable coils in an acute stage, and resulted in good outcome. PPPIA with basilar bifurcation aneurysm has not been presented or reported in the literature to date. To our knowledge, this is the first report of such an association of vascular anomalies. The frequency of PPPIA combined with the intracranial aneurysm is relatively high, whereas the occurrence of PPPIA is extremely rare. Therefore, it was suggested that some congenital and/or hemodynamic factors changed by PPPIA may affect the pathogenesis of intracranial aneurysms.     

Continuous postoperative monitoring of cortical blood flow and intracranial pressure

A new technique to continuously monitor cortical blood flow and intracranial pressure in postoperative patients is described. A thermal diffusion flow probe with a pressure port is left in contact with the cortex at craniotomy. Postoperative intracranial pressure--cortical blood flow can be monitored and acute changes or trends are readily detected. The thermal flow probe has been previously compared with radioactive xenon (133Xe) clearance and hydrogen clearance methods of measuring cortical blood flow in animals. The technique gives a real-time quantitative indication of flow. Changes in cortical blood flow can be observed within a few seconds and the effects of treatment can be readily observed. Changes in flow due to vasospasm have been demonstrated in subarachnoid hemorrhage. It is anticipated that information learned from this method will aid in the management of patients with head trauma, tumors, and subarachnoid hemorrhage.     

Sudden death in a rat subarachnoid hemorrhage model

The pathogenesis of sudden death during subarachnoid hemorrhage (SAH) still remains to be elucidated. A new rat common carotid artery-prechiasmal extracorporeal shunt model was designed to study the effect of different severities of SAH on intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mortality. Different severities of SAH were induced by controlling the bleeding period (from 30 to 90 sec) and number of bleedings (one or three times). SAH caused a dramatic increase in ICP and immediate depression of rCBF, which recovered slowly to a certain extent. ICP increased sharply within the first 30 seconds and reached a plateau concomitant with nearly zero rCBF, which suggested the occurrence of cerebral circulation arrest. Bleeding of more than 60 seconds and increased ICP over 80 mmHg were directly correlated with the mortality. Respiratory arrest was the first sign of death, immediately followed by cardiac depression resulting in sudden death. This model combines arterial bleeding with systemic blood pressure and controlled bleeding time to simulate the acute period of SAH.