Transient Immunoglobulin-Like Molecules Are Present in the Subplate Zone and Cerebral Cortex during Postnatal Development

A monoclonal antibody (mAb SP-1) labels subplate neurons ofthe cat visual cortex but does not stain the remnants of thesubplate neuronal population that comprise the interstitialcells of adult cortical white matter. mAb SP-1 was shown previouslyto recognize a cytosolic polypeptide of 56 kDa (Naegele et al.,1991). We have now characterized the distribution of SP-1 immunoreactiveneurons in the visual cortex and carried out additional biochemicalstudies at a range of postnatal ages in various tissues. Brain,liver and serum were found to contain the previously identified56 kDa polypeptide. This polypeptide was also recognized bya cat immunoglobulin antiserum. The epitope recognized by mAbSP-1 was present on cat IgG Fc fragment but not cat IgG Fabfragment. By 4 weeks postnatal, levels of the 56 kDa antigendecreased in cortex and an additional higher molecular weightSP-1 reactive polypeptide of 75 kDa was detected. In the maturecortex, both polypeptides were absent from cytosolic fractions.Immunocytochemical staining comparing the distributions of SP-1(SP-1+) and anti-IgG (lg+) immunoreactive neurons showed completecolocalization in subplate neurons beneath primary visual cortex.By 4 weeks, some pyramidal neurons in cortical areas 17 and18 were weakly positive for SP-1 but negative for IgG. At subsequentages, the immunoreactive staining became progressively fainteruntil it was no longer detectable in white or gray matter ofadult cat visual cortex.     

Neuronal Units Linked to Microvascular Modules in Cerebral Cortex: Response Elements for Imaging the Brain

How neuronal activity changes cerebral blood flow is of biologicaland practical importance. The rodent whisker-barrel system hasspecial merits as a model for studies of changes in local cerebralblood flow (LCBF). Stimulus-evoked changes in neural firingand ‘intrinsic signals’ recorded through a cranialwindow were used to define regions of interest for repeatedflow measurements. Whisker-activated changes in flow were measuredwith intravascular markers at the pia. LCBF changes were alwaysprompt and localized over the appropriate barrel. Stimulus-relatedchanges in parenchymal flow monitored continuously with H₂ electrodesrecorded short latency flow changes initiated in middle corticallayers. Activation that increased flow to particular barrelsoften led to reduced flow to adjacent cortex. Dye was injectedinto single penetrating arterioles from the pia of the fixedbrain and injected into arterioles in slices of cortex wherebarrels were evident without stains. Arteriolar and venulardomains at the surface were not directly related to underlyingbarrels. Capillary tufts in layer IV were mainly coincidentwith barrels. The matching between a capillary plexus (a vascularmodule) and a barrel (a functional neuronal unit) is a spatialorganization of neurons and blood vessels that optimizes localinteractions between the two. The paths of communication probablyinclude: neurons to neurons, neurons to glia, neurons to vessels,glia to vessels, vessels to vessels and vessels to brain. Matchinga functional grouping of neurons with a vascular module is anelegant means of reducing the risk of embarrassment for energy-expensiveneuronal activity (ion pumping) while minimizing energy spentfor delivery of the energy (cardiac output). For imaging studiesthis organization sets biological limits to spatial, temporaland magnitude resolution. Reduced flow to nearby inactive cortexenhances local differences.     

Neurotransmitter Control of Neocortical Neuronal Activity and Excitability

The pattern of activity and excitability of cortical neuronsand neuronal circuits is dependent upon the interaction betweenglutamatergic and GABAergic fast-activating transmitter systemsas well as the state of the more slowly acting transmitterssuch as ACh, norepinephnne, 5-HT, and histamine. Through theactivation of GABAA_A receptors, GABAergic neurons regulate theamplitude and duration of EPSPs and, in so doing, control thelevel of functional activation of NMDA receptors. In contrast,activation of muscarinic, adrenergic, serotoninergic, his taminergic,and glutamate metabotropic receptors con trols the excitabilityand pattern of action potential gen eration in identified pyramidalcells through increases or decreases in various K⁺ conductances.Activation of muscarinic,      

Nonuniform Alteration of Dendritic Development in the Cerebral Cortex Following Prenatal Cocaine Exposure

Prenatal exposure to cocaine has the potential to modify normalbrain development and result in behavioral dysfunction. We useda new animal model in which cocaine was administered intravenouslyduring prenatal development in pregnant rabbits twice dailyat low dosages. Analysis of brain development focused on twoareas of the cerebral cortex, anterior cingulate and primaryvisual, in which dopamine afferents, a target of cocaine, aredifferentially distributed. All postnatal rabbits exposed tococaine prenatally exhibited normal features of cortical organization,including thickness, lamination patterns, and cytoarchitectonicdifferentiation. General axonal and astroglial organization,assessed by neurofilament-H and glial fibrillary acidic proteinimmunostaining, also was unchanged in the cocaine-exposed animals.Analysis of dendritic organization was done using antibodiesagainst microtubule-associated protein 2 (MAP2), which revealsmostly the larger apical shafts of cortical pyramidal cells.In the anterior cingulate cortex of adolescent rabbits exposedto cocaine in utero, there is a marked decrease in both dendriticbundling and typical long, straight MAP2-stained profiles. Innormal animals, the long, bundled dendrites are readily tracedin a single focal plane from layer III or V pyramidal cell somatato the pial surface in saline-treated animals. Instead, thedrug-exposed animals contained many more short segments of MAP2-staineddendrites that could be viewed coursing in and out of the planeof focus in the sections. Apical dendrites in mature visualcortex appeared normal in the cocaine-exposed rabbits. Examinationof MAP2 staining at various postnatal ages revealed that thedendritic changes expressed in the adolescent anterior cingulatecortex appeared less robust, but still evident at birth. ByP10–14, dendritic modifications were similar to the adultCounts of the number of MAP2-positive dendritic profiles crossingthe layer II–III interface reached a nadir of 50% in thecocaine-exposed animals, indicative of a change in the organizationof the apical dendrites compared to the control animals. Dendriticprofiles of anterior cingulate neurons, filled by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyaninepercholate (Dil), confirmed that in the cocaine offspring, thedendrites coursed in an irregular, wavy manner from deep tosuperficial layers, suggestive of dendrites that were longerthan normal, although cortical thickness was unchanged. Thealtered dendritic profiles also were seen in Golgi-impregnatedneurons. The data indicate that prenatal exposure to cocainecan lead to specific alterations of neuronal growth that arelong lasting. The lack of dendritic changes in visual cortexsuggests that the drug does not modify development of corticalregions uniformly. This study also provides a new focus on theanterior cingulate cortex as a site in which aberrant structure-functionrelationships following prenatal cocaine exposure should beexamined in both animal models and clinically.     

Burst Activation of the Cerebral Cortex by Flash Stimuli during Isoflurane Anesthesia in Rats

Background: The degree of suppression of sensory functions during general anesthesia is controversial. Here, the authors investigated whether discrete flash stimuli induced cortical field potential responses at an isoflurane concentration producing burst suppression and compared the spatiotemporal properties and frequency spectra of flash-induced burst responses with those occurring spontaneously.

Methods: Rats were equipped with multiple epidural and intracortical electrodes to record cortical field potentials in the right hemisphere at several locations along the anterior-posterior axis. At isoflurane concentrations of 1.1, 1.4, and 1.8%, discrete light flashes were delivered to the left eye while cortical field potentials were continuously recorded.

Results: Isoflurane at 1.4-1.8% produced burst suppression. Each flash produced a visual evoked potential in the primary visual cortex followed by secondary bursting activity in more anterior regions. The average latency and duration of these bursts were 220 and 810 ms, respectively. The spontaneous and flash-induced bursts were similar in frequency, duration, and spatial distribution. They had maximum power in the frontal (primary motor) cortex with a dominant frequency of 10 Hz.     

Neuronal Organization in Area 17 of Cat Visual Cortex

An antibody to microtubule-associated protein 2 (MAP2) has beenused to examine the arrangements of neurons in striate cortexof the cat. It is found that the apical dendrites of medium-sizedand large pyramidal cells in layer V group together to formclusters that have a center-to-center spacing of about 56 µm.As these clusters ascend, the apical dendrites of pyramidalcells in layer ll/lll are added to them. The thinner apicaldendrites of the smaller pyramidal cells in layer VIa also formgroups that are referred to as bundles. These bundles ascendinto layer IV independent of the clusters, and their arrangementsuggests that the bundles are formed so that the apical dendritesof the layer VIa pyramids can pass between the groups of cellbodies of the layer V neurons. It is proposed that the clusters formed from the apical dendritesof the layer V and layer ll/lll pyramidal cells represent theaxes of vertical modules of pyramidal cells, which representthe basic neuronal aggregates within area 17 of cat visual cortex.And it is suggested that these modules can be recruited in variouscombinations, most obviously by the excitation provided by thethalamic inputs, to form the functional columns, such as theones that are concerned with eye preference and orientation.Based upon the distribution of the dendritic clusters, the pyramidalcell modules would have diameters of 56 µm, and sincethey are considered to extend through the depth of the cortex,each one would contain some 203 neurons. The striate cortexof one hemisphere contains 160, 000 of these modules, whichis about the same as the number of X-cells projecting to onehemisphere from the dorsal lateral geniculate nucleus and twicethe number of X- or ß-ganglion cells in the retina.The form of the pyramidal cell modules in cat striate cortexis compared to those present in monkey striate cortex, in whichthe similar modules are about 10 times more numerous, but only31 µm in diameter (Peters and Sethares, 1991a).     

Computational Methods for Reconstructing and Unfolding the Cerebral Cortex

We describe computational methods for constructing three-dimensionalmodels and unfolded, two-dimensional maps of the cerebral cortex.These methods consist of four procedures, including (1) samplingof a surface within the cortex. (2) reconstruction of a three-dimensionalmodel of that surface, (3) unfolding of the surface to generatea two-dimensional cortical map, and (4) visualization of dataon the model and the map. These methods produce structurallyaccurate representations of the cortex and have practical advantagesover previous manual and automated approaches for flatteningthe cortex. We illustrate the application of these methods toneuroanatomical data obtained from histological sections ofcerebral cortex in the macaque monkey. The approach should beequally useful for structural and functional studies in otherspecies, including humans.     

Well-Preserved Cholinergic Neuronal Activity in the Brain Cortex of the Severely Uremic Rats

Abstract

Incidence of acute kidney injury (AKI) in patients with pyogenic liver abscess is rare. In our study we found AKI in 32.6% of patients with liver abscess. Majority of the patients were in their fifties and sixties. As per acute kidney injury network trial criteria, renal failure was in stage 1 in 26.6%, stage 2 in 40%, and stage 3 in 33.3% of the patients. Dialysis support was needed in 26%. All patients except one recovered from AKI.     

Cerebral Cortex Activation during Experimentally Induced Ventilator Fighting in Normal Humans Receiving Noninvasive Mechanical Ventilation

Background: Mechanical ventilation is delivered to sedated patients during anesthesia, but also to nonsedated patients (ventilator weaning, noninvasive ventilation). In these circumstances, patient-ventilator asynchrony may occur, provoking discomfort and unduly increasing work of breathing. In certain cases, it is associated with an increased inspiratory load. Inspiratory loading in awake humans activates the premotor cortical regions, as illustrated by the occurrence of electroencephalographic premotor potentials. In normal humans during noninvasive ventilation, the authors used an experimental model of patient-ventilator asynchrony to determine whether premotor cortical activation occurs in this setting.

Methods: Noninvasive pressure support ventilation was administered to seven healthy volunteers aged 22-27 yr with continuous electroencephalographic recordings in Cz. The ventilator settings were first adjusted to make the subjects feel comfortable ("comfort"), and then modified to induce respiratory "discomfort" (evaluated on a 10-cm visual analog scale). This was achieved by setting the ventilator to a higher trigger level, reducing the slope of the pressure support rise, and reducing the level of pressure support. The settings were finally brought back to their initial values. To identify a respiratory-related premotor activity, a minimum of 80 preinspiratory electroencephalographic epochs were averaged.

Results: Altering ventilator settings induced respiratory discomfort (average visual scale 4 [1.5-6.0] vs. 0 [0-1.0] cm during "comfort"; P < 0.0001). This was associated with premotor potentials in all cases, which disappeared upon return to "comfort."     

Identification of Proteins Downregulated during the Postnatal Development of the Cat Visual Cortex

To identify proteins that play a role in the development ofthe mammalian visual cortex, we have used an immunosuppressionand rapid immunization strategy to generate monoclonal antibodiesto antigens that are present in area 17 of the cat during thepeak of cortical plasticity but are downregulated near the endof the plastic period. We report here the immunohistochemicaland immunobiochemical characterization of six monoclonal antibodiesthat identify antigens preferentially expressed in the cat visualcortex at 5 weeks of age. Monoclonal antibodies Cat-305 and Cat-306 detect three immunoreactiveelements that are not present at birth but are present at 5weeks. The majority of immunoreactivity is associated with apopulation of cells in the white matter that are absent at 15weeks of age. At both 5 and 15 weeks, a very small number ofneurons show intense immunoreactivity throughout all processes,resembling that achieved with a Golgi stain. In addition, adiffuse band of immunoreactivity in layer IV is largely restrictedto cortical areas 17 and 18. Cat-307 recognizes a 150 kDa soluble protein present in smallcytoplasmic inclusions. These cytoplasmic "dots" are presentin all layers, but are most prominent in layer V. Cat-307 immunoreactivityis present at birth and is completely downregulated by 15 weeks.Cat-104 and Cat-105 recognize a 200 kDa insoluble protein presentat birth and at 5 weeks, but markedly downregulated by 15 weeks.At birth, the white matter, subplate, and layer I are most denselylabeled, while at 5 weeks labeling is densest in layers II,III, and V. Cat-402 recognizes a number of high-molecular-weightantigens that are differentially expressed at 5 and 15 weeksof age. Stained non-neuronal cells that resemble protoplasmicastrocytes are present in all layers at both 5 and 15 weeks.At 5 weeks, but not at birth or 15 weeks, darkly immunoreactiveradial processes are observed that run through the full depthof the cortex. We show here that immunoreactivity for several different monoclonalantibodies is detected selectively during the period of maximaldevelopmental plasticity. The results demonstrate that the catvisual cortex at 5 weeks of age is molecularly distinct fromthe cortex at 15 weeks.     

Effect of the α2-Agonist Dexmedetomidine on Cerebral Neurotransmitter Concentrations during Cerebral Ischemia in Rats

Background: This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone.

Methods: Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 [mu]g/kg; infusion: 25 [mu]g [middle dot] kg-1 [middle dot] h-1). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 [mu]g/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and p H were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography.

Results: During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia.     

Developmental Changes Revealed by Immunohistochemical Markers in Human Cerebral Cortex

The developing human cerebral cortex is distinguished by a particularlywide subplate, a transient zone in which crucial cell-cell interactionsoccur. To further understand the role of the subplate in humanbrain development, we have studied the immunohistochemical expressionof certain neuronal (GAP-43, MAP-2 parvalbumin) and astroglial(vimentin, GFAP} markers in the developing visual cortex fromgestational ages of 14 weeks to 9 months post-term. At 14–22weeks, immunoreactivity to GAP-43, a protein involved in axonaloutgrowth, was most prominent in the subplate and marginal zoneneuropil and in the fibers of the radiations running near theventricular zone; at 22–42 weeks, GAP-43 immunoreactivefibers were observed in the maturing cortical plate. Immunoreactivityfor the microtubule-associated protein MAP-2 was present inthe differentiating cortical plate at 14 weeks, but at 22–42weeks was most prominent in the somata and dendrites of differentiatedneurons, particularly the Cajal-Retzius neurons of the marginalzone, in neurons of the subplate and in those forming corticallayer 5. Parvalbumin immunoreactivity did not appear until 26weeks, when stained neurons were in a sparse band of cells inlayer 6 and upper subplate. Vimentin and GFAP did not staindifferentiated neuronal cells. Vimentin immunoreactivity appearedearly in neuroepithelial and radial glial cells, decreasingafter 35 weeks, with a concomitant increase in GFAP immunoreactivityin radial glial and maturing astrocytic cells. Our results showthat despite the greater complexity of the developing humanneocortex, molecular markers are expressed in spatial and temporalpatterns similar to those observed in non-human primates, carnivoresand rodents. These protein markers should prove useful in developmentalstaging, and in providing a framework in which to examine congenitaldisorders of cerebral development.     

NADPH-Diaphorase-Positive Neurons in Primate Cerebral Cortex Colocalize with GABA and Calcium-Binding Proteins

Neurons in the monkey cerebral cortex containing nicotinamideadenine dinucleotide phosphate-diaphorase (NADPH-d) can he dividedinto two distinct types, both nonpyramidal. Type I neurons havea large soma (diameter 20–50 µm), a dense NADPH-dhistochemical reaction. and are distributed throughout the cortex,but mainly in the subcortical white matter, and are mostly aspiny.Type II cells have a small soma (< 20 µm) with lightNADPH-d reactivity and are distributed primarily in the supragranularlayers, particularly layers II and upper III. The numericaldensity of type II cells is much greater than that of type I.Type I neurons also stain for GABA and a few intracortical typeI cells contain calbindin. All type II cells found here arecolocalized with both GABA and calbindin. Neither type I nortype II cells are stained for parvalbumin. Together with previous observations that almost all corticalNADPH-d cells in various subprimates are like type I cells,we suggest that type II cells may form a group of NADPH-d-richneurons differentiated in higher mammalian cortex from a subpopulationof calbindin-containing GABAergic interneurons, and these nitricoxide-synthesizing cells may play a role in control of intracorticalneuronal activity characteristic of higher cerebral functionsin advanced mammals.     

Nitric Oxide Synthase and Cytochrome C Oxidase Changes in the Tumoural and Peritumoural Cerebral Cortex

Summary. Summary. Background: We analysed changes in nitric oxide synthase (NOS) and cytochrome oxidase (CO) activities in the tumoural and peritumoural cerebral cortex in order to investigate: a) the role of NO in tumourigenesis, in TBF regulation, and in vasogenetic PBE; b) the metabolic changes caused by the neoplasm in the surrounding tissues. Method: Intra-operative samples of cerebral cortex were studied by means of immunohistochemistry for nNOS and iNOS, and by histochemistry for NADPH-diaphorase (NADPH-d) and CO. Findings: In contrast with normal cortex, reactive glial cells and the endothelium of small blood vessels displayed strong NADPH-d and iNOS activities in oedematous peritumoural tissue. In the tumoural cortex, NADPH-d and nNOS-positive neurones were reduced in number and their dendrites were thin and interrupted, and infiltrates of NADPH-d and iNOS-positive tumoural cells were frequent. CO activity was decreased in the deep layers of peritumoural cortex, and it was almost absent in the tumoural cortex. Interpretation: In peritumoural and tumoural cortex changes in NOS and CO activities suggest that the coupling between neuronal activity and blood flow is impaired in the damaged cerebral cortex, and that the increase in NOS activity may play a role in tumour vascularization and progression.     

Development of Inferior Temporal Cortex in the Monkey

Inferior temporal (IT) cortex is critical for visual patternrecognition in adult primates. However, the functional developmentof IT cortex appears to be incomplete until late in the firstyear of life in monkeys and probably beyond. Responses of neuronsin IT are substantially weaker, of longer latency, and moresusceptible to anesthesia within at least the first half yearof life. In addition, refinement of connections of IT, particularlythose with regions in the opposite hemisphere and with regionsrelated to memory and attention, continues for at least severalmonths after birth. Moreover, many of the pattern recognitionfunctions that IT supports in adulthood themselves show a veryprotracted period of development, and damage to IT cortex ininfancy appears to have relatively little effect on patternrecognition abilities, despite the pronounced effects of comparabledamage in adulthood. These findings all suggest that IT undergoesan extended period of postnatal development, during which bothvisual experience and the maturation of other brain structuresmay contribute to the emergence of mechanisms of pattern recognitionwithin IT. In other respects, fundamental characteristics of IT emergequite early. For example, despite their weaker responses, ITneurons have adult-like patterns of responsiveness—includingpronounced form selectivity and large bilateral receptive fields—asearly as we were able to test (     

Metabolic Changes in the Cerebral Cortex of the Rat Induced by Intravenous Pentothalsodium®

The effects of thiopental on cerebral metabolism were evaluated by means of measurements of cerebral metabolic rate for oxygen (CMR_o2) and of tissue levels of organic phosphates, glycolytic substrates, citric acid cycle intermediates and selected amino acids. Shortly after the beginning of thiopental administration, CMR_o2 was reduced to half the normal value, and there were signs of retardation of glycolytic flux at the phosphofructokinase step. Inhibition at this regulatory enzymatic step could be related to an increase in phosphocreatine and a fall in inorganic phosphate concentration. The rise in phosphocreatine, and the unchanged levels of ATP, ADP and AMP demonstrate that induction of anaesthesia with thiopental is unrelated to energy failure.
Changes in citric acid intermediates included a fall in malate, and probably also in citrate, α-ketoglutarate and fumarate, with a tendency towards reduction in the pool of citric acid cycle intermediates; and the amino acid changes were dominated by a progressive rise in aspartate. It is suggested that these changes are secondary to a reduced rate of pyruvate delivery, and to a decrease in malate/oxaloacetate ratio.     

Restoration of Oxygen Uptake and Blood Flow in the Rat Cerebral Cortex after Halothane Anaesthesia

Halothane decreases both the certal blooi Row (CBF) and the cerebral metabolic rate for oxygen (CMRo₂) when given in anaesthetic doses. A recent report (G jedde & H indfelt 1975) suggests that when halothane is administered to rats for 1 hour, CBF and CMRo₂ are depressed by about 30 and 40%, respectively, for as long as 4 hours after discontinuation of the halothane anaesthesia. In the present study rats were anaesthetized with 1% halothane for 1 hour, and CBF and CMRo₂ were measured at the end of a 30 min recovery period, during which 70% N₂O was administered. Comparison with animals maintained on 70% N₂O throughout the entire 90 min period showed that previous halothane anaesthesia had no effects on CBF or CMRo₂.     

Isoflurane-induced Cerebral Hyperemia in Neuronal Nitric Oxide Synthase Gene Deficient Mice

Background: Nitric oxide (NO) has been reported to play an important role in isoflurane-induced cerebral hyperemia in vivo. In the brain, there are two constitutive isoforms of NO synthase (NOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Recently, the mutant mouse deficient in nNOS gene expression (nNOS knockout) has been developed. The present study was designed to examine the role of the two constitutive NOS isoforms in cerebral blood flow (CBF) response to isoflurane using this nNOS knockout mouse.

Methods: Regional CBF (rCBF) in the cerebral cortex was measured with laser-Doppler flowmetry in wild-type mice (129/SV or C57BL/6) and nNOS knockout mice during stepwise increases in the inspired concentration of isoflurane from 0.6 vol% to 1.2, 1.8, and 2.4 vol%. Subsequently, a NOS inhibitor, Nomega -nitro-L-arginine (L-NNA), was administered intravenously (20 mg/kg), and 45 min later, the rCBF response to isoflurane was tested again. In separate groups of wild-type mice and the knockout mice, the inactive enantiomer, Nomega -nitro-D-arginine (D-NNA) was administered intravenously in place of L-NNA. Brain NOS activity was measured with radio-labeled L-arginine to L-citrulline conversion after treatment with L-NNA and D-NNA.

Results: Isoflurane produced dose-dependent increases in rCBF by 25 +/- 3%, 74 +/- 10%, and 108 +/- 14% (SEM) in 129/SV mice and by 32 +/- 2%, 71 +/- 3%, and 96 +/- 7% in C57BL/6 mice at 1.2, 1.8, and 2.4 vol%, respectively. These increases were attenuated at every anesthetic concentration by L-NNA but not by D-NNA. Brain NOS activity was decreased by 92 +/- 2% with L-NNA compared with D-NNA. In nNOS knockout mice, isoflurane increased rCBF by 67 +/- 8%, 88 +/- 12%, and 112 +/- 18% at 1.2, 1.8, and 2.4 vol%, respectively. The increase in rCBF at 1.2 vol% was significantly greater in the nNOS knockout mice than that in the wild-type mice. Administration of L-NNA in the knockout mice attenuated the rCBF response to isoflurane at 1.2 and 1.8 vol% but had no effect on the response at 2.4 vol%.     

完全性缺血后再灌流时神经元死亡的多因素分析

目的：探讨完全性缺血后再灌流时神经元死亡的主要参与因素，方法：９６只新西兰兔随机分为两组，１组为未缺血对照组，Ⅱ组为缺血后再灌流组，后者再分为ａ，ｂ和ｃ三个亚组，分别在缺血３０ｍｉｎ后再灌流３０、１８０和３６０ｍｉｎ。利用四血管夹闭模型造成３０ｍｉｎ完全性脑缺血，检测脑组织中２８项生化参数的变化，并用计算机图象分析技术，将大脑１２个区域的神经元分为Ａ、Ｂ、Ｃ和Ｄ四类。对生化参数水平和四类神经元计数