Developmental spectrum of the excitotoxic cascade induced by ibotenate: a model of hypoxic insults in fetuses and neonates

Ibotenate, a glutamatergic agonist, was used to study the spectrum of excitoxic disturbances at different ages of cerebral development. Cultures of whole mouse embryo were submitted to ibotenate at E8 for 20 h: during the phase of early premigratory differentiation; ibotenate did not induce any detectable histological lesion. During migration of supragranular neurons, newborn hamsters intracerebrally injected at P0 with ibotenate display neuronal migration disorders graded from nodular heterotopias to extensive laminar heterotopias mimicking some aspects of lissencephalic and double-cortex syndromes. After completion of neuronal layer V, P0 mice injected with ibotenate exhibit laminar neuronal depopulation of layer V-VIa mimicking human micro-gyria. At P5 in mouse, after completion of neuronal migration of the cortical plate, ibotenate induces neuronal loss in all cortical layers and the formation of porencephalic cysts. This study emphasizes the dramatic role played by glutamate in brain development, in the occurrence of neuronal migration disorders in the cortex. and in grey and white matter damage.     

Cerebral venous malformation complicated by spontaneous thrombosis

A case of spontaneous thrombosis and infarction leading to death as complications of a cerebral venous malformation in a 13-yearold boy is reported. This is the first published report of this type of complication occurring in a case of venous angioma. While the biologic behavior of cerebral venous malformations has suggested that they are benign in nature, and the results of surgical management have encouraged a conservative approach, the present case illustrates a potential complication and argues against the assumption that these malformations are completely benign in nature.     

Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.     

Outcome in Children With Significantly Abnormal Cerebral Blood Flow Detected by Doppler Ultrasonography: Focus on the Survivors

BACKGROUND AND PURPOSE: The Doppler waveform patterns of loss of diastolic flow, appearance of retrograde diastolic flow, or no detectable flow in the cerebral arteries suggest significantly abnormal cerebral blood flow (CBF). A retrospective study was performed to show that significantly abnormal CBF alone, without clinical criteria, is not necessarily specific to brain death in the young pediatric population. PATIENTS AND METHODS: Forty-seven pediatric patients, from newborn to 4 years of age, were found to have significantly abnormal CBF, including 7 patients with loss of diastolic flow, 28 with retrograde diastolic flow, and 23 with no detectable cerebral flow on serial Doppler sonographic examinations. Their clinical data and sonographic results were collected and analyzed. RESULTS: Forty-two patients died, a few of whom had only transient improvement of cerebral flow. All of the patients with no detectable cerebral flow expired. Five patients survived with or without sequelae. Their underlying conditions that caused increased intracranial pressure were treated by medical and/or surgical intervention, and diastolic reversal of CBF corrected within 1 day in all 5. CONCLUSIONS: Although no detectable flow is a lethal sign, pediatric patients with loss or reversal of diastolic flow may survive with prompt and effective treatment. Using Doppler ultrasound to diagnose cerebral circulatory arrest should be done with caution in pediatric patients.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours

In 10 patients subjected to craniotomy for supratentorial cerebral tumours in neurolept anaesthesia, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice peroperatively by a modification of the Kety & Schmidt technique, using 133Xe. The relative CO2 reactivity was assessed indirectly as the % change of the arteriovenous oxygen difference (AVDO2) per mm change in PaCO2. The patients were premedicated with diazepam 10-15 mg perorally. For induction, thiopentone 4-6 mg/kg, droperidol 0.2 mg/kg and fentanyl 5 micrograms/kg were used, and for maintenance N2O 67% and fentanyl 4 micrograms/kg/h. During the first flow measurement the median and range of CBF was 30 ml/100 g/min (range 17-45), of AVDO2 8.0 vol % (range 4.1-9.5), and of CMRO2 2.28 ml O2/100 g/min (range 1.57-2.84). During the second CBF study, AVDO2 increased to 9.3 vol % (range 3.4-11) (P less than 0.05), and CMRO2 increased to 2.51 ml O2/100 g/min (range 1.88-3.00) P less than 0.05, while CBF was unchanged. The CO2 reactivity was present in all studies, median 1.8%/mmHg (range 0.5-15.1). The correlation coefficients between jugular venous oxygen tension/saturation, respectively, and CBF were high at tensions/saturations exceeding 4.0 kPa and 55%, indicating that hyperperfusion is easily unveiled by venous samples from the jugular vein during this anaesthesia.     

Channges in regional cerebral blood flow after hyperventilation in the pig with an induced focal cerebral contusion

Summary Changes in regional cerebral blood flow in anaesthetized pigs with an induced focal cerebral contusion were studied before and after two grades of hyperventilation. A reduction in arterial tension of CO₂ with 0.70mmHg and a further reduction of 0.55mmHg did not change the CO₂ reactivity. Reactivity in both injured and macroscopically normal regions was the same, revealing an average of 39.3% flow change per kPa change in CO₂ tension. Regions with low flow after the contusion had an equally big reduction apparently leading to hypoxia because global metabolic rate was unchanged.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Incremental Value of Three-Dimensional Echocardiography Over Transesophageal Multiplane Two-Dimensional Echocardiography in Qualitative and Quantitative Assessment of Cardiac Masses and Defects

In the present study, we compared three-dimensionally (3-D) reconstructed images with multiplane two-dimensional (2-D) transesophageal echocardiographic (TEE) images in 17 patients with various cardiac masses and defects. To overcome the problem of making measurements from 3-D reconstructed images, we carefully "dissected" the 3-D dataset using paraplane and anyplane 2-D sections, which were then used to obtain the maximum sizes of the cardiac masses and defects. Of the 15 vegetations and 9 abscesses detected by 3-D TEE in 7 patients, only 8 (53%) vegetations and 4 (44%) abscesses were detected by multiplane 2-D TEE (P < 0.02). Also, the exact anatomical location, shape, geometry, and extent of various cardiac masses and defects were more clearly delineated by 3-D than 2-D TEE. The maximum dimensions of cardiac masses and defects were larger by 3-D than by 2-D TEE in 17 (89%) of the 19 lesions available for comparison (P < 0.002). In addition, 3-D TEE correlated more closely than 2-D TEE when compared to surgical measurements in three patients in whom they were available. Thus, it would appear that in several instances, the exact size of the cardiac lesion could only be assessed by analysis of the 3-D volumetric dataset. Out preliminary study has demonstrated the superiority of transesophageal 3-D reconstruction over multiplane 2-D TEE in both qualitative and quantitative assessment of various cardiac mass lesions and pathological defects.     

电针对沙鼠急性脑缺血再灌注后神经原损伤的保护作用

本实验利用沙鼠急性脑缺血再灌注模型，研究电针对脑缺血及再灌注各期脑电活动的影响及组织病理学的改变。结果表明：缺血１０ｍｌｎ，脑电幅度受到严重抑制，甚至变平坦，总功率大大下降，再灌注后总功率难以恢复，在１２０ｍｉｎ时仅恢复到缺血前的２７．３９±１１．３１％，以后即不再进一步恢复，电针组动物缺血１０ｍｉｎ再灌注后，脑电的恢复明显比对照组快，１２０ｍｉｎ时恢复至缺血前的７１．４５±１６．４６％（Ｐ＜０．０１），２４０ｍｉｎ时继续恢复至缺血前的７５．２７±１８．４３％。同时电针能明显减轻缺血１０ｍｉｎ后再灌注２４小时的神经原缺血性损伤。结果提示：电针对急性脑缺血引起的神经原损伤具有保护作用，并能促进脑功能的恢复。