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.

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 (ICBF) 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 ICBF 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.     

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]     

兔皮质引流静脉急性闭塞模型的建立

目的通过双极电凝闭塞皮质引流静脉,建立兔脑皮质引流静脉急性闭塞模型。方法青紫蓝兔35只,随机分为3组,其中A组15只,电凝顶叶皮质引流静脉1支;B组15只,电凝顶叶、枕叶皮质引流静脉各1支;C组(假手术组)5只,仅行开颅加切开硬脑膜处理,3组在造模后8h、24h、48h分别进行DSA检查,脑含水量、脑梗死率和静脉血栓形成率统计,大体标本、光镜对照研究。结果电凝法闭塞兔皮质引流静脉的成功率为100%,造模后经DSA证实所有电凝闭塞的皮质引流静脉已完全闭塞。A、B两组脑组织含水量与C组比较,均有升高(均P0.01),B组造模后8h、24h、48h较A组对应时段脑组织含水量均明显增高(均P0.01)。B组相邻2支皮质引流静脉电凝闭塞后的脑梗死率和静脉血栓形成率较A组均明显增加(均P0.05),假手术组均未见上述异常表现。结论电凝法制作的皮质引流静脉闭塞模型成功率高,稳定性和重复性好,是研究皮质静脉闭塞的理想模型。     

The effect of large dose dexamethasone on local cerebral blood flow (L-CBF) in ischemic rat brain

Changes of local cerebral blood flow (l-CBF) were estimated by autoradiographic techniques in middle cerebral artery occlusion rats given a large dose of (3 mg/kg) dexamethasone. The sensory-motor, parietal, auditory and olfactory cortices showed a significant reduction (greater than 25%) of l-CBF. In MCA occlusion with large dose dexamethasone group, ischemic cortices showed significant reduction from the only MCA occlusion group (highest 36%). There was no significant reduction of l-CBF in the deep structures. The effects of dexamethasone on drains with various pathologies have been studied both clinically and experimentally with many kinds of techniques. These effects are now being reevaluated. Still controversial however, is the mechanism that determines whether dexamethasone has beneficial, non-beneficial, or harmful effect. This study may help us to unravel the mechanism of steroid effects, as well as the relationship between corticosteroid and central nervous system.     

Efficacy of retrograde perfusion of the cerebral vein with verapamil after focal ischemia in rat brain

BACKGROUND AND PURPOSE: For treatment of acute stroke, drug therapy administered systemically has been unreliable due to inadequate delivery of drug into ischemic tissue. We have developed a new method to deliver drugs into the ischemic tissue by retrograde perfusion of the cerebral vein. METHODS: We examined in rats the effectiveness of administering verapamil into ischemic tissue by retrograde perfusion through the cerebral vein, starting 3 hours after occlusion of the middle cerebral artery. Twenty-four Fischer-344 rats with occlusion of the middle cerebral artery were divided into four groups of six rats each. Group A rats had no treatment, group B rats received verapamil intravenously, and groups C and D rats received verapamil by transvenous perfusion of the brain with blood and with saline, respectively. We studied local cerebral blood flow using the autoradiographic method with carbon-14-labeled iodoantipyrine and examined cerebral infarct volume with cresyl violet and Luxol fast blue staining. RESULTS: As compared with group A rats, in groups C and D rats we found a significant and extensive increase of cerebral blood flow in the ischemic cortical and subcortical areas (55-119%, p less than 0.05) and a significant reduction of cerebral infarct volume (31-39%, p less than 0.05). We found no significant changes in group B rats. CONCLUSIONS: This study shows that transvenous perfusion of the brain with verapamil starting 3 hours after occlusion of the middle cerebral artery produces a significantly beneficial effect in rats.     

The focal brain ischemia with disturbance of venous drainage]

The focal brain ischemia with disturbance of cerebral venous drainage often lead to brain edema and hemorrhagic infarction and make mortality and morbidity worse. So we tried to make sure of this fact using a middle cerebral artery (MCA) occlusion model in adult cat. The MCA was exposed by the transorbital approach and temporally obstructed by Zen's clip. We divided the animals into two groups of eight cats. One group is only MCA occlusion group (sham group) and the other in MCA occlusion with disturbance of venous drainage (VRD group). We ligated bilateral external jugular vein (EJV) and internal jugular vein (IJV) and injected embolic sources from the left EJV to obstruct the venous system of cat brain. The pressure of superior sagittal sinus was increased up to 18.7 +/- 5.3 mmHg by this method. A cranial window was made above the ectosylvian gyrus, which has poor anastomosis. The reactivity of pial arteriole and regional cerebral blood flow (rCBF) were observed through the window. And histological brain examination was also performed. The result was that the reactivity of pial arterioles was severely disturbed in VRD group. The area of cerebral infarction and edema were also significantly expanded in VRD group. Considering from these facts, when the venous drainage was disturbed, cerebral perfusion pressure relatively decrease. Because of the decrease in cerebral perfusion pressure, cerebral infarction and edema probably expand to the area so called penumbra.     

The temporary occlusion of middle cerebral artery in cats--the correlation between the rCBF and the histological changes (author's transl)

The correlation between the changes of regional cerebral blood flow (rCBF) and the histological changes were examined using the middle cerebral arterial (MCA) occlusion model in cats. A total of 24 adult cats were tracheostomized and anesthetized by inhalation of halothane. The right MCA was clipped by the transorbital approach. Two hours after the application, the clip was removed and the brain was recirculated for two hours. Then, the brain was perfusion-fixated and the histological studies were carried out. The animals were separated into two groups according to the severity of histological damages using light and electron microscope. Severe cortical damage was present in 8 cats (Group A). In the remaining 16 cats, little or no cortical damage was found (Group B). The averaged rCBF values before occlusion were 45.4 +/- 2.3 ml/100 gm/min in group A and 46.5 +/- 1.6 in group B, showing no statistically significant difference. Between these two groups, however, there was a statistically significant difference in the averaged rCBF values during the ischemic period. In group A, the averaged rCBF values during MCA occlusion was only 6.8 +/- 0.9 and in group B, it was 25.3 +/- 0.8. In the recirculation period, there was a prompt and uniform recovery of rCBF in group B. Whereas in group A, a marked diversity of rCBF ranging from oligemia to hyperemia ensued. This is presumably a reflection of inhomogeneous blood flow, or patchy non-filling of the cerebral cortex. The critical values of rCBF as to the occurrence of severe cortical damage in two-hours MCA occlusion is considered to lie between the lowest value of group B and the highest value of group A, i.e., around 12--15 ml/100 gm/min.     

The effects of disturbance of cerebral venous drainage on focal cerebral blood flow and ischemic cerebral edema

The effect of disturbance of cerebral venous drainage on acute ischemic cerebral edema and cerebral circulation were studied by measuring local cerebral blood flow (LCBF) and local changes in brain water content using a middle cerebral artery (MCA) occlusion model. Rats were anesthetized with halothane and the stem of the left MCA was occluded. Disturbance of cerebral venous drainage was induced by bilateral occlusion of the external jugular veins, i.e., the right external jugular vein was cannulated and the left one was occluded by a clip. LCBF was measured by the 14C-iodoantipyrine (14C-IAP) autoradiographic method at 2 hours after MCA occlusion. Local changes in brain water content were studied 2 hours after MCA occlusion by measuring the specific gravity of cerebral tissue in the gradient column with bromobenzene and kerosene. The control rats which underwent the same anesthesia and surgical procedure including the MCA occlusion and cannulation into the right external jugular veins, but which did not undergo occlusion of the left external jugular veins, were prepared and studied at the same time after MCA occlusion. In the rats with bilateral occlusion of the external jugular veins, the external jugular venous pressure was evaluated up to about 8 mmHg (100 mmH2O) (control: 1.3 mmHg). At 2 hours after MCA occlusion, LCBF in the ischemic core was decreased. The ischemic area was more extensive in the rats with bilateral occlusion of the external jugular veins compared with the controls. Furthermore, specific gravity of the brain was decreased in the entire left MCA territory in the rats with bilateral occlusion of the external jugular veins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transvenous perfusion of the brain with verapamil during focal cerebral ischemia in rats

We report on the effect of calcium channel blocker verapamil administered into the inferior cerebral vein in rats 1 hour after occlusion of the middle cerebral artery. Twenty-four rats were divided into four groups of six rats each. Group A rats received no medication. The other three groups received 0.1 mg verapamil/kg/2 hr. Group B rats received verapamil intravenously. Group C and D rats received verapamil and autologous arterial blood by transvenous perfusion of the brain, Group C rats at 100 mm Hg perfusion pressure and Group D rats at 150 mm Hg perfusion pressure. The administration of verapamil started 1 hour after middle cerebral artery occlusion and lasted for 2 hours. Three hours after occlusion, we used double- or single-tracer autoradiography with 4-[18F]fluoroantipyrine or [14C]iodoantipyrine and [14C]alpha-aminoisobutyric acid as tracers to study the brains for local cerebral blood flow and blood-brain barrier permeability changes. Group C showed a significant increase of local cerebral blood flow in the parietal cortex (89%, p less than 0.01) and sensorimotor cortex (64%, p less than 0.05) compared with Group A. Group D showed an extensive and striking increase in local cerebral blood flow of the ischemic cortical and subcortical areas (57-100%, p less than 0.05). Group B showed no significant changes but exhibited further reduction of local cerebral blood flow in the ischemic cerebral hemisphere associated with slightly increased local cerebral blood flow in the nonischemic cerebral hemisphere compared with Group A. There was no change of blood-brain barrier permeability in any group.(ABSTRACT TRUNCATED AT 250 WORDS)     

ASICs3在重度脑挫裂伤及周边水肿区域的表达及相关性研究

目的 研究重度脑挫裂伤患者挫伤区域和周边水肿1 cm和2 cm区域酸敏感离子通道3( ASICs3)的表达,及与pH值和钙离子相关蛋白的表达关系.方法 分析了27例经影像学和手术证实的脑挫裂伤患者,分别取材挫伤区域(B组)、挫伤周边非功能区1 cm区域(A组)和2 cm区域(C组),行ASICs3 Western blot检测,挫伤脑组织pH值检测,免疫荧光钙调蛋白检测,并做对照分析.结果 A组pH值为6.10±0.04,B组pH值为7.18±0.04,C组为6.85±0.05,A组pH值与B、C组相比较差异有显著性意义(P＜0.05);ASICs3的表达B组较A组和C组明显上调,A组可以看到较B组和C组更多密集的免疫荧光钙调蛋白颗粒.结论 ASICs3的表达在脑挫伤区域较周边水肿区域明显上调,脑挫伤周边1 cm水肿区域组织代谢明显,脑损害较重.钙超载和ASICs3蛋白表达及组织代谢有密切关系.     

Pathophysiological studies in moyamoya disease by rCBF and cortical artery pressure measurements in comparison to those in ICA or MCA occlusion

The authors measured preoperative rCBF and intraoperative cortical artery pressure (CAP) during STA-MCA anastomosis to investigate cerebral hemodynamics in moyamoya disease. Six of 13 patients including 3 children showed ischemic attack and the remaining presented hemorrhagic attack. rCBF was measured by single photon ECT with Xe-133 inhalation technique. CAP's and rCBF's in moyamoya disease were compared to those in the 22 internal carotid artery (ICA) and 8 middle cerebral artery (MCA) occlusion. Systemic arterial blood pressure (SABP) was obtained at the radial artery. Mean rCBF in the MCA territory in moyamoya disease, ICA occlusion, and MCA occlusion were 39, 37, and 33 ml/100 g/min respectively. Mean SABP and CAP in moyamoya disease were 103 and 28 mmHg, respectively. In ICA occlusion, mean SABP and CAP were 98 and 45 mmHg, respectively. In MCA occlusion, mean SABP and CAP were 89 and 36 mmHg, respectively. To clarify the hemodynamics, vascular resistance was obtained from the following equations: The proximal vascular resistance (Rp), which was produced from the cervical ICA to cortical artery, was obtained by (mean SABP - mean CAP)/(rCBF). And distal vascular resistance (Rd) which was produced from the cortical artery to jugular vein, was obtained by (mean CAP)/(rCBF). Mean Rp in moyamoya disease ICA occlusion and MCA occlusion were 2.01, 1.21 and 1.70, respectively. Rd in moyamoya disease, ICA occlusion and MCA occlusion were 0.79, 1.37 and 1.22, respectively. There were significant differences in Rp and Rd between moyamoya disease and ICA or MCA occlusion. In ischemic group in moyamoya disease, rCBF, SABP, CAP, Rp and Rd were 41 ml/100 g/min, 111 mmHg, 28 mmHg, 1.92 and 0.70, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse.

Recent findings in animals emphasize that experimental ischemic brain damage can be strikingly reduced by estrogen: however, the neuroprotective mechanisms are not well understood. It was hypothesized that estrogen signaling via cognate estrogen receptors (ERs) within the vasculature is an important aspect of cerebral ischemic protection in the female brain, in part by amplifying intraischemic cerebral blood flow (CBF). In the present study, the hypothesis that chronic treatment with the pure ER antagonist ICI182,780 (ICI) would increase ischemic brain damage by a blood flow-mediated mechanism was investigated. Adult C57B1/6J mice were pretreated with either subcutaneous ICI (100 microg/day) or oil/ethanol vehicle for 1 week before 2 hours of middle cerebral artery occlusion (MCAO) and 22 hours of reperfusion. End-ischemic regional CBF was evaluated in additional cohorts using [14C]iodoantipyrine autoradiography. Infarction volume as measured by cresyl violet histology was greater in the striatum of ICI-treated females (70 +/- 3% of contralateral striatum vs. 40 +/- 12% in vehicle-treated females). Cortical injury was not enhanced relative to control animals (39 +/- 6% of contralateral cortex in ICI group vs. 27 +/- 8% in vehicle-treated group). Physiologic variables and ischemic reduction of the ipsilateral cortical laser-Doppler flow signal were similar between groups. Further, ICI treatment did not alter end-ischemic cortical or striatal CBF. The deleterious effect of ICI was limited to females, as there were no differences in stroke damage or CBF between male treatment groups. These data suggest that estrogen inhibits ischemic brain injury in striatum of the female by receptor-mediated mechanisms that are not linked to preservation of intraischemic CBF.     

Incidental Diagnosis of Cerebral Cortical Venous Thrombosis in Postdural Puncture Headache on Brain Computed Tomography

Diagnosis of cerebral cortical venous thrombosis in patients with postdural puncture headache (PDPH) is usually secondary to changes in headache pattern or cerebral infarctions. Nevertheless, incidental discovery of asymptomatic forms on brain imaging has never been reported before and its management thus remains ill‐defined. We describe 2 cases of patients with asymptomatic cortical vein thrombosis in the context of PDPH. In both cases, brain computed tomography (CT) scans showed an isolated cortical vein thrombosis without cerebral damage. Neurological examination revealed the typical orthostatic feature of PDPH, independently of cortical vein thrombosis which was considered as a radiological incidental finding. Clinical and radiological signs resolved after bed rest, oral caffeine, and anticoagulation therapy. Asymptomatic cortical vein thrombosis may be found on radiological exploration, even basic like brain CT scan without contrast, of PDPH. Utility of anticoagulation therapy, which could increase the risk of cerebral hemorrhagic complications in this specific context, has to be assessed.     

Transtentorial diaschisis: reduction of cerebellar blood flow caused by supratentorial local cerebral ischemia in the gerbil

To assess the effect of supratentorial cerebral ischemia on infratentorial brain function, changes in regional cerebellar blood flow (rCeBF), after right carotid occlusion for 4 hours, were studied in 30 mongolian gerbils. The regional cerebral blood flow (rCBF) in the occluded cerebral hemisphere and rCeBF in both cerebellar hemispheres were measured simultaneously by hydrogen clearance methods. Before carotid occlusion, rCBF was 0.44 +/- 0.07 ml/g brain/min, and rCeBF in the left and right cerebellar hemispheres was 0.37 +/- 0.09 and 0.40 +/- 0.09 ml/g brain/min, respectively. After carotid occlusion, rCBF decreased in all animals showing levels of above 0.20 ml/g brain/min in 14 (group A), between 0.10 and 0.19 ml/g brain/min in 7 (group B) and below 0.10 ml/g brain/min in 9 (group C). rCeBF exhibited no changes in group A and a mild reduction in group B after carotid occlusion. In group C, rCeBF was significantly reduced 30 min after carotid occlusion in the left cerebellar hemisphere followed subsequently by bilateral reduction. In groups B and C, supratentorial brain edema was observed 4 hours after occlusion, but the degree of edema was moderate. The results of the present study suggest that depression of infratentorial brain function may occur after supratentorial local cerebral ischemia, presumably due to diaschisis.     

Impairment of autoregulation following cortical venous occlusion in the rat

Recent experiments showed an upward shift of the lower limit of autoregulation (AR) following photochemical occlusion of cortical veins in the rat. The goal of the present study was to prove the hypothesis that occlusion of cortical veins will be associated with impairment of the upper limit of autoregulation as well. In n = 28 Wistar rats unilateral frontoparietal cranial windows were drilled for transdural assessment of regional cerebral blood flow (rCBF) by laser Doppler scanning. The animals were allotted to two groups: (1) Group A (n = 5), control group for determination of the upper limit of autoregulation with stepwise induced arterial hypertension by intravenous administration of the alpha adrenergic drug methoxamine under continuous monitoring of mean arterial blood pressure (MABP); (2) Group B (n = 23), in which two cortical veins were photochemically occluded with rose bengal dye and fiberoptic illumination upon baseline CBF measurement. This was followed by repeated rCBF measurements under AR testing. Loss of AR in control Group A with passive increase of rCBF occurred at MABP of 147.5 +/- 2.9 mmHg. In Group B venous occlusion was followed by an initial phase of reduced rCBF, and then by pressure passive increases, thereby indicating loss of AR. Statistically significant changes of rCBF when compared to baseline MABP occurred at MABPbaseline + 10% (112.7 +/- 6.6 mmHg). We conclude that AR is impaired upon cortical venous occlusion with the propensity for hyperperfusion injury at a lower level of MABP when compared with a control group. In the context with earlier findings this may lead to narrowing of the corridor for MABP management following intra-operative occlusion of large cortical veins.     

Effect of long-term administration of JTP-2942, a novel thyrotropin-releasing hormone analogue, on neurological outcome, local cerebral blood flow and glucose utilization in a rat focal cerebral ischemia

The effect of JTP-2942, a novel thyrotropin-releasing hormone analogue on neurological examination, local cerebral blood flow (l-CBF) and local cerebral glucose utilization (l-CGU) were examined when JTP-2942 was administered for 4 weeks after 1 week reperfusion following ischemia in a rat middle cerebral artery (MCA) occlusion. Left middle cerebral artery ischemia was induced for 90 min followed by reperfusion. JTP-2942 (0.03 or 0.003 mg/kg) or saline (vehicle) were administered for 4 weeks after 1 week ischemia, and then the drug was withdrawn. Neurological symptoms and motor disturbance based on inclined plane test were measured once a week after 1 week ischemia. l-CBF and l-CGU were measured by quantitative autoradiographic technique after 6 weeks ischemia. The adjacent sections subjected to l-CBF or l-CGU measurement were stained with Hematoxylin-Eosin, and the infarction volume was measured. JTP-2942 (0.03 mg/kg) significantly ameliorated neurological symptoms and motor disturbance at 5 weeks after ischemia as compared with vehicle, and then after completion of drug administration, amelioration effect continued. JTP-2942 (0.03 mg/kg) also significantly ameliorated the reduced l-CBF and l-CGU in the peri-infarcted areas such as the frontal cortex, motor cortex and medial caudate-putamen. No significant differences were noted in the infarction volume among MCA occlusion rats. This indicates that activating reduced metabolic turnover associated with synaptic connection changes or the activation of compensation mechanisms may result in improvement of neurological symptoms and motor disturbances. It is therefore expected that JTP-2942 may be a possible therapeutic agent for motor disturbance during the subacute or chronic cerebral infarction.     

Regional cerebral blood flow in relation to MRI and EEG findings in tuberous sclerosis.

To identify the focus of paroxysmal neuronal activity causing epilepsy in tuberous sclerosis (TS), the regional cerebral blood flow (r-CBF) in 19 patients with TS was assessed using single-photon emission computed tomography (SPECT) with I-123 iodoamphetamine (IMP), in correlation with serial interictal EEGs and organic changes observed on magnetic resonance imaging (MRI). There was a general irregularity of cortical IMP uptake and retention in TS, and two-thirds of the cerebral regions exhibiting high intensity in T2-weighted MRI images (cortical tubers) showed a decrease in r-CBF. In addition to in tubers, decreased r-CBF was observed in regions in which MRI was considered to indicate destruction of the normal cortex, atrophy or vascular abnormalities, although these areas did not consistently show epileptic changes in serial EEGs. Among the cortical regions which consistently showed epileptic foci in serial EEGs, none showed abnormal r-CBF without lesions on MRI. We conclude that IMP-SPECT is useful for visualizing the epileptogenic laterality in cases with bilateral MRI lesions and EEG epileptic changes, and to differentiate epileptogenic foci from electrophysiological propagated areas. However, regarding the severity of epilepsy, the MRI findings showed a better correlation than the IMP-SPECT findings did.     

Effect of long-term administration of ethyl eicosapentate (EPA-E) on local cerebral blood flow and glucose utilization in stroke-prone spontaneously hypertensive rats (SHRSP)

The objective of this study was to determine the effect of ethyl eicosopentate (EPA-E) on local cerebral blood flow (l-CBF) and local glucose utilization (l-CGU) in specific regions of the brain in stroke-prone spontaneously hypertensive rats (SHRSP). EPA-E (100 mg/kg body weight) or saline was orally administered to 8-week-old SHRSP. L-CBF and l-CGU in the EPA-E-treated, saline-treated, and 8-week-old control rats were measured autoradiographically using ¹⁴C-iodoantipyrine and ¹⁴C-deoxyglucose (Sakurada's and Sokoloff's methods). The l-CBF of the saline-treated group decreased significantly with age in all areas measured. EPA-E treatment alleviated the age-dependent decrease in l-CBF in all areas, especially those in the basal ganglia. The l-CGU of the saline-treated group did not change with age, however EPA-E treatment increased l-CGU in all areas measured, though the changes were not significant. EPA-E ameliorated the decrease in cerebral blood flow and improved glucose metabolism in SHRSP suffering from severe hypertension. These results suggest that EPA-E may be useful in the prevention of stroke.     

大鼠局灶性脑缺血再灌注后LPA1的表达对神经元凋亡的影响

目的 探讨大鼠局灶性脑缺血再灌注后溶血磷脂酸受体1(LPA1)的表达对神经元凋亡的影响及其可能机制。方法 将24只SPF级SD雄性大鼠随机分为4组,每组各6只,分别为假手术组(A组)、大脑中动脉栓塞(MCAO)组(B组)、MCAO+溶剂组(C组)、MCAO+LPA1拮抗剂(Ki16425)组(D组); 4组均于手术后48 h取标本; 利用HE染色观察大鼠脑组织细胞形态的变化; 四氮唑红(TTC)染色观察大鼠脑梗死面积; 免疫荧光技术检测LPA1在大鼠皮层半暗带神经元表达水平; 免疫印迹、免疫组化技术检测大鼠脑组织中Caspase-3蛋白及p-Akt蛋白表达水平。结果 与A组比较,B组有明显的缺血再灌注损伤,表现为细胞肿胀,细胞溶解坏死,大鼠皮层半暗带神经元的LPA1表达水平较高; 与C组比较,D组大鼠脑梗死面积显著增大(P<0.05),缺血半暗带细胞肿胀更加明显,胞浆空泡区增大,细胞核固缩更加严重,细胞间隙增宽更明显; D组较C组缺血半暗带Caspase-3蛋白表达水平明显升高(P<0.05),而p-Akt蛋白表达水平明显降低(P<0.05)。结论 抑制大鼠局灶性脑缺血再灌后LPA1的表达可使大鼠脑梗死面积增大,细胞凋亡增加,同时p-Akt蛋白表达减少,这说明在大鼠局灶性缺血再灌注过程中LPA1对神经元具有保护作用,其机制可能是通过Akt途径来发挥保护作用的。