Regional changes in cerebral blood flow and blood-brain barrier permeability during epileptiform seizures and in acute hypertension in rabbits

Interrelationship between the breakdown of the blood-brain barrier (BBB) to Evans blue and elevations in the regional cerebral blood flow (rCBF) was studied in rabbits subjected to adrenaline- or metaraminol-induced systemic hypertension and also in bicuculline-induced seizures. The rCBF was assessed in small samples from various regions of the brain with the use of [3H]nicotine, and the permeability of the BBB was evaluated with an Evans blue tracer. In acute hypertension, Evans blue extravasations were observed in the occipital cortex and sometimes in the superior colliculus, i.e., the regions which also showed the highest elevations in rCBF. The breakdown of the BBB in acute hypertension was clearly related to the rate of mean arterial blood pressure rise, being much less pronounced in the metaraminol group, which showed a much slower blood pressure elevation rate. In bicuculline-induced seizures, there was no evident correlation between the amplitude of rCBF elevations and Evans blue extravasations. Preservation of BBB integrity was observed in areas showing high elevations in the rCBF.     

Regional cerebral perfusion abnormalities in developmental language disorder

Objective A voxel based investigation of cerebral blood flow was conducted to identify brain functional differences during resting state between children with developmental language disorder (DLD) and normal controls. Method Using DSM–IV criteria, we selected 21 children with DLD.All children were examined by technetium–99m–HMPAO Brain SPECT. Using SPM analyses, we compared the SPECT images of children with DLD and those of 17 control subjects on a voxel by voxel basis using ANCOVA covarying for age. Results Reduced cerebral blood flow in the right putamen,the right inferior parietal cortex, and the left globus pallidus were found in children with DLD versus the controls. However, no area of increased cerebral blood flow was observed in children with DLD compared to the controls. Conclusion Though results should be interpreted cautiously, this study confirms the presence of functional defects in the basal ganglia and the inferior parietal lobe during the resting state of the brains of children with DLD. It also gives further evidence for functional deficits in basal ganglia as an important factor in the etiology of DLD.     

Imaging of cerebral perfusion in acute stroke

Rapid imaging of cerebral perfusion in acute stroke is needed for timely triage of patients for thrombolytic therapy. Accurate quantitative perfusion imaging is required for proper assessment of penumbral brain parenchyma truly at risk for extension of infarction from the irreversible core infarction. CT and MRI techniques offer rapidity and availability for acute stroke imaging, including that of cerebral perfusion. CT perfusion techniques are readily available, but suffer from limited brain coverage of present multislice scanners. MRI offers whole brain coverage, but suffers from less availability and higher cost than CT. Presently, development is directed towards increasing the quantitative accuracy of cerebral perfusion imaging and validation of surrogate parameters, such as time to peak (TTP). In the future, the need for rapid and frequent assessment of cerebral perfusion and its metabolic correlates, with minimal or no radiation, will probably be met by MRI.     

Regional cerebral blood flow decreases during chronic and acute hyperglycemia

The presence of hyperglycemia prior to stroke or cardiac arrest can increase neuronal damage caused by brain ischemia. Acute hyperglycemia shows this effect in animal models of stroke. However, chronic hyperglycemia and chronic hyperglycemia with additional acute elevation of blood glucose are more common premorbid states for stroke patients. The effect of chronic hyperglycemia on regional cerebral blood flow (rCBF) is unclear but blood flow changes may play a role in this ischemic cell damage. We measured rCBF in awake restrained rats that had chronic hyperglycemia induced by treatment with streptozotocin. This was compared to that measured in rats made acutely hyperglycemic by injecting glucose into the peritoneal space. rCBF was measured in 17 brain regions using [14C]iodoantipyrine. During chronic hyperglycemia, when plasma glucose was 29 microns/ml, rCBF was decreased and a regional distribution of this effect was noted; 9 hindbrain regions showed a mean flow decrease of 14% while forebrain regions demonstrated less flow reduction. Acute elevation of plasma glucose during normoglycemia or superimposed on chronic hyperglycemia produced flow reductions of 7% for each 10 microns/ml increment in plasma glucose up to 60 microns/ml. Both chronic and acute hyperglycemia are associated with decreased rCBF and the mechanism for this effect does not appear to adapt to chronic hyperglycemia.     

Regional cerebral blood flow in acute experimental allergic encephalomyelitis

Regional cerebral blood flow was studied in Lewis rats with fulminant acute experimental allergic encephalomyelitis (EAE). [14C]iodoantipyrine was used as a tracer. By employing a short experimental time and an infusion schedule producing an increasing arterial tracer concentration, the spatial resolution of the method was fine enough to detect focal increases in blood flow in the small central nervous system lesions (lymphocytic accumulations). An increase of flow of 100% in the lesions and a decrease of 50% in the cerebral cortex of EAE animals was statistically significant. In all other regions studied (deep cerebral structures, cerebellum), blood flow in EAE animals did not differ from the control values. The flow increase corresponding to the lesions may be due to inflammatory hyperemia. The cortical decrease in flow may be secondary to sensory motor impairment.     

Regional cerebral blood flow during alcoholic blackout

Regional cerebral blood flow was measured during alcoholic blackout in a 61-year-old man with a blood-alcohol level of 0.38%. The mean flow level was found to be elevated by about 30-60% compared to repeated studies during long-term abstinence. The regional pattern did not change greatly. Increases of mean regional cerebral blood flow have previously been reported during social drinking and in Wernicke-Korsakoff's syndrome. A common disturbance of subcortical activation systems is hypothesized.     

Regional cerebral blood flow decreases during hyperglycemia

The presence of hyperglycemia before brain ischemia increases stroke-related morbidity and mortality in experimental animals and humans. However, little is known of the effect of hyperglycemia on regional cerebral blood flow (rCBF). Acute hyperglycemia was induced in awake but restrained rats by intraperitoneal injection of 50% D-glucose. Regional flow was determined using [14C]iodoantipyrine and quantitative autoradiography. Elevation of plasma glucose from 11 to 39 mM was associated with a 24% reduction in rCBF when compared with controls that received normal saline. Intraperitoneal D-mannitol produced an elevation of plasma osmolality equivalent to that observed with glucose. However, rCBF was only reduced by 10%. Hyperglycemia appears to produce a global decrease in rCBF in awake rats that cannot be completely explained by the attendant increase in plasma osmolality. If a similar influence is present during brain ischemia, hyperglycemia could extend areas of critical flow limitation.     

Regional variation in the response of cerebral ornithine decarboxylase to electroconvulsive shock

Levels of ornithine decarboxylase activity were measured in brain regions and in adrenal glands of adult male rats exposed to electroshock. Five hours after shock at levels causing transient loss of consciousness and fore and hindlimb tonic extensor seizures, major increases in ornithine decarboxylase activity were found in adrenals, hippocampus; brain stem, frontal cortex, and cerebellum, but striatal levels were unchanged. These increases were reversed by 24 h after electroshock. When lower levels of shock, which caused no loss of consciousness, were also used, a clear dose-response relationship of shock intensity and ornithine decarboxylase activity was found for hippocampus and brain stem. The ornithine decarboxylase response in brain increased with higher shock levels. However, the changes of ornithine decarboxylase in adrenal glands were maximal at intermediate, and diminished at maximal shock values, as were levels of circulating testosterone. These data suggest a differing role for cerebral and adrenal ornithine decarboxylase in the mature rat. The brain enzyme may be primarily related to metabolic repair processes, whereas adrenal ornithine decarboxylase may function in the activation of secretion.     

Regional cerebral blood flow during hypoxia-ischemia in immature rats

Immature rats subjected to a combination of unilateral common carotid artery ligation and hypoxia sustain brain damage confined largely to the ipsilateral cerebral hemisphere. To ascertain the extent and distribution of ischemic alterations in the brains of these small animals, we modified the Sakurada technique to measure regional cerebral blood flow using carbon-14 autoradiography. Seven-day-old rats underwent right common carotid artery ligation following which they were rendered hypoxic with 8% O2 at 37 degrees C. Before and during hypoxia, the rat pups received an injection of iodo[14C]antipyrine for determination of regional cerebral blood flow. Blood flows to individual structures of the ipsilateral cerebral hemisphere were not influenced by arterial occlusion alone; flows to the contralateral hemisphere and to the brainstem and cerebellum actually increased by 25-50%. Hypoxia-ischemia was associated with decreases in regional cerebral blood flow of the ipsilateral hemisphere such that by 2 hours, flows to subcortical white matter, neocortex, striatum, and thalamus were 15, 17, 34, and 41% of control, respectively. The hierarchy of the blood flow reductions correlated closely with the distribution and extent of ischemic neuronal necrosis. However, unlike the pathologic pattern of this model, the degree of ischemia appeared homogeneous within each brain region. Blood flows to contralateral cerebral hemispheric structures were relatively unchanged from prehypoxic values, whereas flows to the brainstem and cerebellum nearly doubled and tripled, respectively. Thus, ischemia is the predominant factor that determines the topography of tissue injury to major regions of immature rat brain, whereas metabolic factors (intrinsic vulnerability) may influence the heterogeneous pattern of damage seen within individual structures.     

Plasma thrombomodulin changes in acute cerebral infarction or hypertension patients*★ An observation for verification

BACKGROUND： Thrombomodulin concentration greatly increases in plasma when vascular endothelial cells are injured, and it is one of the specific molecular markers for endothelial injury. OBJECTIVE： To analyze the plasma levels of thrombomodulin after cerebral infarction or hypertension, and to compare levels with those from healthy control subjects. DESIGN： A case-controlled observation. SETTING： Yuquan Hospital of Tsinghua University. PARTICIPANTS： Patients with hypertension （n = 37） and acute cerebral infarction （n = 26） were selected from the outpatient and inpatient Department of Neurology, Yuquan Hospital of Tsinghua University from February 2003 to February 2006. The cerebral infarction group consisted of 24 males and 2 females, 36-77 years of age, with a mean age of 62 years. All patients fulfilled the diagnosis criteria for cerebral infarction, according to the diagnostic standards revised by the Second National Academic Meeting for Cerebrovascular Disease, and were confirmed by CT or MRI. The hypertension group consisted of 27 males and 10 females, 36-77 years of age, with a mean age of 56 years. These patients fulfilled the diagnostic criteria for hypertension set by WHO. In addition, 43 healthy physical examinees were selected as the control group, consisting of 23 males and 20 females, 35-67 years of age. Informed consent was obtained from all participants. METHODS： In the cerebral infarction group, thrombomodulin plasma levels were determined by enzyme-linked immunoabsorbent assay at days 1, 3, 7, and 14 after attack. Thrombomodulin plasma levels were determined only once in the hypertension group and the control group. The results from the cerebral infarction group were compared with those from the hypertension group and the control group. MAIN OUTCOME MEASURES： Level of thrombomodulin in plasma. RESULTS： All 63 patients and 43 healthy volunteers were included in the final analysis of results. （1） At 7 days after the attack, the plasma levels of thrombomodulin in the cereb     

CT脑灌注成像指导下的急性前循环脑梗死溶栓治疗

目的 探讨以CT脑灌注成像(CTP)指导下的急性前循环脑梗死溶栓治疗的优越性.方法 通过对比分析5例急性前循环脑梗死者"时间窗"、"缺血半暗带"、和溶栓干预疗效之间的相关关系,阐析以CTP结果指导下的急性前循环脑梗死溶栓治疗的优越性.结果 对急性前循环脑梗死患者进行CTP检查,如显示有缺血半暗带,即使超过溶栓时间窗,仍可进行溶栓治疗(本组有2例效果较好);对在溶栓时间窗内的患者,如CTP显示已有脑梗死形成,对该类患者进行溶栓治疗疗效欠佳(本组有3例).结论 以时间窗为指导的溶栓干预模式存在固有的局限性,对急性前循环脑梗死患者应行CTP检查,根据缺血半暗带来判断是否溶栓治疗,是一种较为理想的模式.     

急性脑梗死的320排动态容积CT脑灌注成像研究

目的研究320排动态容积CT全脑灌注成像(CTP)在脑梗死患者中的价值。方法对2014-01—2016-01驻马店市中心医院收治的33例脑梗死患者采取CT全脑灌注成像检查,测量梗死核心区、缺血半暗带(IP)与健侧镜像区的脑血流量(CBF)、脑血容量(CBV)、达峰时间(TTP)及平均通过时间(MTT)值,计算梗死核心区及IP的相对脑血流量(rCBF)、相对脑血容量(rCBV)、相对达峰时间(rTTP)、相对平均通过时间(rMTT),并进行对比分析。结果 33例患者中,头颅平扫发现9例早期脑梗死征象,其余24例未发现异常。33例患者行CTP成像均发现异常灌注区,其中25例存在IP;与健侧镜像区对比,CBV无显著差异(P0.05),而TTP、MTT值明显延长,CBF显著降低,差异有统计学意义(P0.05);与梗死核心区对比,CBF、CBV升高,TTP缩短,MTT延长,差异均有统计学意义(P0.05)。IP区与梗死核心区rCBF、rCBV、rTTP、rMTT对比,差异有统计学意义(P0.05)。10例超急性期(发病6h以内)、15例急性期(发病6~72h)中11例、8例亚急性期(发病72h~14d)中4例存在IP。缺血半暗带分期:Ⅰ2期6例,Ⅱ1期12例,Ⅱ2期7例。结论 320排动态容积CT全脑灌注成像可通过注射一次对比剂获得常规CT、CTP、CTA数据,对脑梗死患者的病变部位、范围及有无IP等提供明确的影像学依据,且可对IP进行分期,为临床实现对患者的个体化治疗提供了可能,且显著降低了患者所受的辐射剂量,安全性高。     

Decrease in perfusion of cerebral capillaries during incomplete ischemia and reperfusion

The effect of unilateral, incomplete cerebral ischemia on CBF, unidirectional flux of alpha-aminoisobutyric acid (AIB) and sodium, and number of perfused capillaries during ischemia and reperfusion was measured in the cortex of gerbils with symptomatic ischemia. Three hours of unilateral carotid occlusion reduced the CBF to the ipsilateral cortex by 81%, with a smaller 30% decrease in the contralateral cortex. Following 11 min of reperfusion, CBF in the ipsilateral cortex returned to the preischemic value, while the contralateral blood flow decreased to 50% of control. The transfer constants for AIB and sodium in the ipsilateral cortex were reduced by 67 and 53%, respectively, after 3 h of ischemia, with no change in the contralateral cortex. The transfer constant for AIB remained decreased by 48% during the first 20 min of reperfusion, while that for sodium returned to its control value. The number of perfused capillaries was reduced 54% by 3 h of ischemia and remained decreased by 20% after 11 min of reperfusion. These data indicate that 3 h of unilateral carotid occlusion reduces the number of perfused capillaries in the ipsilateral cortex during the ischemic period. Further, the early reperfusion phase is characterized by a mismatch between capillary perfusion and CBF. Finally, early in the postischemic phase, sodium transport undergoes a selective stimulation, probably as a result of stimulation of ion transport.     

CT灌注成像对急性缺血性脑卒中半暗带的评估

目的探讨CT灌注成像(CT perfusion imaging,CTPI)对急性缺血性脑卒中半暗带的评估。方法应用16层螺旋CT对21例急性缺血性脑卒中患者行CTPI检查,于1w后复查CTPI,分析梗死区和半暗带的相对脑血流量(relative cerebral blood flow,rCBF)、相对脑血容量(relative cerebralvolume,rCBV)的数值变化,评估半暗带。结果所有患者的灌注CT图像皆有明确的异常灌注区,病灶中CBF下降,CBV下降或正常,MTT明显延长。梗死区rCBF、rCBV无变化(P>0.05),相对血流量及相对血容量极低;而半暗带区治疗前后rCBF明显改善(P<0.05)、rCBV变化不明显(P>0.05),半暗带区rCBF的可信区间为0.425~0.582。结论CTPI能够对半暗带进行判定,并指导临床的进一步治疗。