Hiroyuki Nakase

Local Cerebral Blood Flow in a Rat Cortical Vein Occlusion Model

The symptoms following sinus and vein occlusion observed in patients and experimental animals display a considerable variability that so far remains largely unexplained. In a rat cortical vein occlusion model using a photochemical thrombotic technique, we examined changes in the cerebral venous flow pattern by fluorescence angiography and regional cerebral blood flow (rCBF) and cerebral blood volume fraction (CBVF) by a modern laser Doppler “scanning” technique. Brain damage was assessed histologically. Fluorescence angiographic findings fell into two groups: group A, rats with an altered venous flow pattern after occlusion (n = 12), and group B, rats with interruption of blood flow and/or a growing venous thrombus (n = 5). In addition, sham-operated animals made up group C (n = 5). Extravasation of fluorescein, a massive decrease in rCBF, a short-lasting increase in CBVF, and regional brain damage were typical for group B. In addition, cortical CBF mapping revealed a transient hyperperfusion zone with hyperemia surrounding a hypoperfused ischemic core in group B. A circulation perturbation following venous occlusion appeared near those occluded cerebral veins without sufficient collateral flow. Furthermore, the venous thrombus continued to grow, accompanied by local critical ischemia and severe brain damage. Conversely, 71% of the animals (12 of 17) tolerated occlusion of a solitary vein without major flow disturbances or histological evidence of damage to the CNS (group A).

Alterations of Regional Cerebral Blood Flow and Oxygen Saturation in a Rat Sinus-Vein Thrombosis Model

BACKGROUND AND PURPOSEnThe pathophysiology of sinus-vein thrombosis (SVT) in patients and experimental animals is still poorly understood. This study was designed to examine and further elucidate the pathophysiological sequence of events, especially the relationship between local and regional blood flow and hemoglobin oxygen saturation (HbSO2) detected at identical locations. The use of both parameters as outcome indicators should be compared.nnnMETHODSnSVT was induced by ligation of the superior sagittal sinus (SSS) and slow injection of kaolin-cephalin suspension into the SSS in rats. Regional cerebral blood flow (rCBF) was assessed by laser-Doppler flowmetry together with regional HbSO2, which was measured by a microspectrophotometric technique at 48 identical locations for 90 minutes after SVT using a scanning technique. Fluorescence angiography was performed before and 30 and 90 minutes after SVT induction. After 48 hours the animals were killed for histology.nnnRESULTSnThe fluorescence angiographic findings could divide animals into three groups: (1) group A, with a solitary SSS thrombus (n=8); (2) group B, with a thrombosis of SSS and cortical veins (n=10); (3) group C, animals that had undergone sham operation (n=5). Decreases of rCBF and HbSO2 and brain damage were seen in group B but not in group A. The reduction of local HbSO2 preceded the flow decrease after sagittal sinus ligation but before thrombosis. Blood pressure in group A was found to be significantly higher after SVT than in groups B and C.nnnCONCLUSIONSnThe brain with acute extension of thrombus from the SSS into cortical veins experiences a critically reduced supply of blood and oxygen. CBF, local HbSO2, and repeated angiography can be helpful monitors for the early detection of critical conditions after SVT. Local HbSO2 has a greater sensitivity to predict outcome than lCBF. Moreover, therapies directed to improve perfusion pressure or reduce vascular resistance may open further therapeutic windows during SVT progression.

Dural arteriovenous fistula of the posterior fossa developing after surgical occlusion of the sigmoid sinus

✓ In this article, the authors present five cases of dural arteriovenous fistula (AVF) that developed in the transverse—sigmoid sinus 2 to 6 years after sacrifice of the sigmoid sinus because of tumor involvement. The original tumor was meningioma in two patients and neurinoma, glomus jugulare tumor, and ameloblastoma in one patient each. The involved sigmoid sinus was resected along with the tumor and ligated at the normal edge; all that remained of the sigmoid sinus was a small stump on the retrosigmoid portion. Serial angiography performed before and after tumor surgery revealed no abnormal arteriovenous communications or dural AVF in any of the cases. Although many reports have suggested that sinus thrombosis is a precipitating factor in the pathogenesis of dural AVFs, this has been difficult to verify because of the small number of cases in which serial angiography was performed before the development of a dural AVF. In all of the cases presented in this article, surgical resection of a dural AVF and...

Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial inhibitor

It was studied whether a subtoxic dose of the mitochondrial neurotoxin, 3-nitropropionic acid (3-NPA), can initiate early-onset tolerance induction for subsequent ischemic injury. Wistar rats were pretreated for 3 h by intraperitoneal 3-NPA (20 mg/kg body weight; n=13) or solvent (n=12). Fifteen minutes global cerebral ischemia was induced by bilateral carotid artery occlusion and hypobaric hypotension. rCBF and tissue hemoglobin oxygen saturation were measured by laser Doppler scanning and a microspectrophotometric method. Ischemic insult and brain temperature were identical in both groups. Body weight and neurological scores recovered in the pretreated group but further deteriorated in the non-treated group (P<0.05). Quantitative histology demonstrated a better neuronal density in neocortex and hippocampal CA2, CA3, and CA4 of pretreated animals (P<0.05).

Evaluation of Absolute Cerebral Blood Flow by Laser-Doppler Scanning – Comparison with Hydrogen Clearance

A major limitation of laser-Doppler (LD) flowmetry, which enables noninvasive and continuous recording of tissue perfusion, is its inability to evaluate the absolute cerebral blood flow (CBF). Using a computer-controlled micromanipulator, the LD scanning technique provides information on the brain microcirculation in many different locations, information which is not available from a single stationary probe. The purpose of the current study was to examine whether LD scanning estimates can be calibrated for the absolute CBF by comparing LD scanning with the hydrogen clearance (HC) method. In Wistar rats (n = 31) including old rats (122–123 weeks old, n = 8), the CBF was altered using the global ischemia model by bilateral carotid artery occlusion coupled with hypobaric hypotension. The CBF was determined simultaneously by the LD scanning technique and HC at each mean arterial blood pressure step, and the correlation of CBF between the two techniques was analyzed. CBF measured by LD scanning was expressed as LD units. Absolute CBF values obtained by methods were correlated (r = 0.87), and the formula to calibrate absolute CBF values from LD units was y = 1.8x – 0.6. On the other hand, in old rats the formula to calibrate the absolute values was different (y = 1.3x + 8.3, r = 0.85). The results suggest that CBF data obtained by LD scanning could be calibrated into absolute blood flow values in particular circumstances, and that LD scanning could compensate in part for the weakness of LD flowmetry.

Clinical Study on Recurrent Intracranial Aneurysms

The authors report 11 cases who underwent reoperations upon for recurrent aneurysms. The initial operations were performed on average 10.1 years earlier for subarachnoid hemorrhage (SAH). The patients’ mean age at the first surgery was 39.7 years. The locations were 9 internal carotid (IC)-posterior communicating artery (PC) and 2 anterior communicating artery (A-com) aneurysms. A residual aneurysmal neck after the first operation was observed in 3 of 10 cases confirmed by postoperative angiography. The primitive-type PC artery was seen in 8 of 9 recurrent IC-PC aneurysms. The recurrent manifestations were SAH in 9 cases. Clipping operations were conducted in 10 and ligation of the IC artery together with extracranial-intracranial bypass in 1 large IC-PC aneurysm. The present study demonstrated two risk factors for aneurysm recurrence, namely, young age and IC-PC aneurysms with a primitive-type PC. Furthermore, direct operation for recurrent aneurysm is often embarassing due to adhesions to the surrounding tissue as a sequela of the previous operation, hence understanding of the anatomical correlation between the old clip and the recurrent portion is important.

The effect of brain compression under venous circulatory impairment.

Abstract It is well known that surgical obliteration of the cerebral veins with additional brain compression by retractors is dangerous. To evaluate the mechanism, we, studied the change in cerebral microcirculation and parenchymal damage following brain compression with venous circulatory impairment using a rat model. The animals were divided into the following four groups (each n = 5) (1) a sham-operated control; (2) group A, one cortical vein occlusion; (3) group B, a 30 mmHg compression pressure; and (4) group C, one cortical vein occlusion with 30 mmHg compression. The cortical vein was occluded photochemically. Local cerebral blood flow (I-CBF) in the compressed area was measured by stationary laser-Doppler (LO) flowmetry and regional CBF (r-CBF) in the surrounding area was also measured by LO scanning technique for 120 min. I-CBF in the compressed area decreased significantly in groups Band C. A gradual and significant increase in group B and decrease in group C in r-CBF of the surrounding area were observed. Histologically, more extensive damage was observed in group C than in group A and B. The degree of hypoperfusion of the affected brain correlated well with the subsequent brain damage in the experiments. We demonstrated that, compared with vein occlusion or brain compression alone, the accumulated episode caused severe ischemia, then increased the vulnerability of the rat brain to tissue damage. [Neural Res 2000; 22: 713-720]

Intermittent isometric exposure prevents brain retraction injury under venous circulatory impairment

Abstract It is recognized that surgical obliteration of the cerebral veins by additional brain compression using retractors is dangerous. However, there is a lack of satisfactory management of this problem. We investigated whether intermittent brain compression can reduce brain injury from cerebral venous circulation disturbances (CVCDs). In Wistar rats (n = 25), a solitary cortical vein was occluded photochemically. The brain surface was compressed by a spring balance and constant compression at 30 mmHg was carried out for 60 min. Intermittent procedure compression protocols included four 15 min compressions at 5 min intervals, intermittent isometric exposure (IM), and intermittent isotonic exposure (IT). Local cerebral blood flow (lCBF) in the compressed area was measured together by laser-Doppler (LD) with the degree of brain compression. After 24 h, the brains were examined histologically. The animals were divided into the following five groups (each n = 5): 1, a sham operated control; 2, cortical vein occlusion (VO); 3, VO + continuous brain compression (CC); 4, VO + IM; and 5, VO + IT. The lCBF decreased significantly during the compression; however, recovery after the series of compressions was observed only in the VO + IM group, not in the VO + CC and the VO + IT groups (p < 0.05). The depth of the brain surface increased stepwise in the VO + IT group compared with the VO + IM group (p < 0.01). The resulting tissue damage was significantly larger in the VO + CC and VO + IT groups than in the vein occlusion group (p < 0.05), but not in the VO + IM group. The results of the present study suggest that intermittent isometric exposure under CVCDs could decrease brain retraction injury during neurosurgical operations and be more beneficial than continuous compression, providing that the compression pressure declines as the process advances. [Neurol Res 2001; 23: 739-744]

A scanning technique to measure regional cerebral blood flow and oxyhemoglobin level

OBJECTIVEThe application of a laser scanning technique to measure regional cerebral blood flow (CBF) and tissue hemoglobin oxygenation (HbO2) using the rat closed cranial window preparation is described. METHODSTwenty-nine male Wistar rats were used to consecutively measure local CBF by laser Doppler flowmetry and tissue HbO2 by a microspectrophotometric method at multiple corresponding cortical locations. The scanning technique used a computer-controlled micromanipulator. Data from three experimental models are presented: the whisker stimulation model, the ischemia-reperfusion model, and the sinus-vein thrombosis model. Sequential changes in local CBF and HbO2 data before, during, and after stimulation, ischemia, and sinus thrombosis were examined. Data from predefined locations within the same region were correlated with the topographical location and then arranged in a three-dimensional image. RESULTSIn the whisker stimulation model, we found a disproportionate increase in CBF (32 ± 12%) as compared with that of HbO2 (9 ± 4%) during stimulation. In the ischemia-reperfusion model, the three-dimensional image showed heterogeneous low CBF (depending on the area) and homogeneous HbO2 at a reduced level during ischemia and postischemic hyperperfusion. However, the range of oxygenation was normal after reperfusion. In the sinus-vein thrombosis model, drainage of the unsaturated blood via the collateral pathways was noted. CONCLUSIONThe laser scanning technique is useful for visualizing sequential changes in hemodynamic-metabolic interactions of cortical brain tissue. This technique can reveal phenomena not detected by traditional monitoring procedures.

Cerebral blood flow and tissue oxygen saturation in immediate and progressive ischemia in rat brain

Abstract The aim of the present study was to investigate whether immediate ischemia is more harmful to the brain than progressive ischemia. To do so, we examined the correlation between the degree and the process of ischemia using hypobaric hypotension technique, which was used to reduce systemic blood pressure acutely or progressively below the lower threshold of CBF regulation, in rat brain. In Wistar rats (n = 21), global ischemia using bilateral carotid arteries occlusion coupled with hypobaric hypotension was induced by lowering mean arterial blood pressure (MABP) progressively to 55, 45 and 35 mmHg or immediately to 35 mmHg. Local cerebral blood flow (lCBF) by laser Doppler (LD) flowmetry and tissue hemoglobin oxygen saturation (HbSO2) by a microspectrophotometric method were measured at 25 corresponding locations using a scanning technique which employs a computer-controlled micromanipulator. Regional CBF (rCBF) and rHbSO2 were determined by calculation of the median value from the 25 ICBF and lHbSO2 data. In the progressive group, rCBF and rHbSO2 decreased gradually and reached 12.2 ± 15.8 LD-units and 44.9% ± 13.4% at 35 mmHg of MABP, respectively. In the immediate group, both parameters dropped suddenly to 7.86 ± 10.6 LD-units (p < 0.01 vs. CBF of the progressive group) and 22.5% ± 15.5% (p < 0.001 vs. tissue HbSO2 of the progressive group) from the control at 35 mmHg. These data suggested that cerebral ischemia is better tolerated if it is induced gradually. CBF recorded by LD-scanning technique and HbSO value by microspectrophotometric method correlated well in the ischemic condition, indicating that HbSO2 can be preserved if CBF is decreased gradually. [Neurol Res 2001; 23: 875-880]