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M Ingvar

Publications and source records attributed to M Ingvar.

At least 55 records · Page 3Linked to original sources
PubMed1995

Brain activation induced by the perceptual maze test: a PET study of cognitive performance.

We investigated with PET the cerebral activation pattern elicited by the perceptual maze test (PMT), a neuropsychological test used to evaluate organic brain injury. The PMT examines visuospatial skill, general intelligence, visually guided motor planning, and the ability to obey rules. Eight right-handed volunteers were examined with PET using the tracer [15O]butanol. Three paradigms containing the PMT, a motor control (SHAM), and a rest condition were examined twice in a randomized order. Solving the PMT caused extensive bilateral activations in the occipital lobe extending rostrally into the parietal lobe and caudally to the posterior part of the temporal lobe. Bilateral activations were also seen in the prefrontal, medial premotor, and the anterior cingulate cortex (ACC). The premotor and primary sensory motor cortices contralateral to the performing hand were also activated. Marked activations were noted in the visual system, including areas pertaining to visuospatial decoding. The previously defined functional network (ACC, prefrontal and posterior parietal cortex) for the maintenance of visuospatial attention was activated during the PMT. Extensive bilateral deactivations were seen in frontomedial, temporal, parietal, and posterior cingulate regions. This pattern may represent relatively decreased blood flow in cortical areas pertaining to sensory modalities that were not activated in the PMT. The decreased activity in these regions could also express diminished cognitive processing in neuronal systems that might interfere with the task-related performance.

Adult↗
PubMed1995

Early [18F]FDG positron emission tomography in infants with hypoxic-ischaemic encephalopathy shows hypermetabolism during the postasphyctic period.

Six full-term infants suffering from perinatal asphyxia and with moderate or severe hypoxic-ischaemic encephalopathy were investigated by positron emission tomography (PET). Regional cerebral metabolic rates of glucose (rCMRgl) were determined using [2-18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans at a median age of 2.5 days (range 2-5 days). Localized increases in rCMRgl were visually observed in five infants. In a subgroup of three infants, absolute values of rCMRgl in different brain regions were calculated. In all cases the results of the PET studies were in good agreement with those of the neuroradiological, neurophysiological and clinical investigations. Information indicating pathophysiological events could be extracted earlier with PET than with conventional morphological imaging techniques. We conclude that [18F]FDG-PET scans performed in critically ill, asphyxiated infants very soon after birth provide valuable information for the prediction about neurological outcome.

Asphyxia Neonatorum↗
PubMed1995

Use of R-beta-[1-11C]hydroxybutyrate in PET studies of regional cerebral uptake of ketone bodies in humans.

A method for determining regional cerebral utilization of ketone bodies in humans is described. After a bolus injection of R-beta-[1-11C]hydroxybutyrate, the time course of the tracer in the brain was measured with positron emission tomography in five healthy volunteers. The regional cerebral blood flow was measured separately. The tracer uptake in the brain could be well described by a single rate constant, indicating that the concentration of unmetabolized ketone bodies in the brain is very low and that transport across the blood-brain barrier is the rate-limiting step. At an average plasma concentration of beta-hydroxybutyrate of 0.043 mumol/ml, the utilization rate was estimated to be 0.48 nmol.ml-1.min-1. In accordance with previous animal studies, the utilization rate was found to increase almost linearly with increasing plasma concentration of beta-hydroxybutyrate. Furthermore, the utilization was higher in gray than in white matter. Finally, the ratio between the utilization in the basal ganglia and the brain as a whole was lower for ketone bodies than for glucose.

3-Hydroxybutyric Acid↗
PubMed1994

Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo.

An experimental drug, 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine, that facilitates glutamatergic transmission in brain after systemic administration was tested for its effects on the induction of long-term potentiation in the hippocampus of rats. Intraperitoneal injections of the drug markedly increased the degree and duration of long-term potentiation; similar results were obtained with an analogue of 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine that was also found to improve retention of memory in a radial maze task and in an odor-matching problem. These results define tools for enhancing long-term potentiation in vivo and confirm an important prediction from the hypothesis that long-term potentiation is a substrate of memory.

Animals↗
PubMed1994

Loss of immunoreactivity for glial fibrillary acidic protein (GFAP) in astrocytes as a marker for profound tissue damage in substantia nigra and basal cortical areas after status epilepticus induced by pilocarpine in rat.

Status epilepticus induced by pilocarpine in rats induces massive tissue damage comprising neurons and astrocytes (incomplete infarction) in substantia nigra pars reticulata (SNR) and in basal cortical areas (BCTX). Immunohistochemistry with a polyclonal antiserum and a monoclonal antibody to GFAP were used here to study the astroglial damage in these regions. Control sections showed a strong labeling for glial fibrillary acidic protein (GFAP) for both antibodies in SNR and BCTX. At 1 day after induction of seizures, labeling with the polyclonal antibodies showed diffuse increase within the lesioned areas and enhanced staining of astrocytes at the border zones. However, staining with the monoclonal antibody was abolished. At 3 days, labeling with both the polyclonal antiserum and the monoclonal antibody was severely reduced within the damaged regions. Reactive astrocytes in the surround of the infarct showed enhanced labeling with both antibodies. This combination of enhanced labeling with polyclonal antibodies and decreased labeling with the specific monoclonal antibody for GFAP can be taken as indicator for acute glial cell damage in seizures and related experimental conditions.

Animals↗
PubMed1994

Immunohistochemical markers for neurons and astrocytes show pan-necrosis following infusion of high-dose NMDA into rat cortex.

This study pertains to the transition between selective neuronal necrosis and the development of cerebral infarction (pan-necrosis). We infused the neuron selective excitotoxin N-methyl-D-aspartate (NMDA) at a relatively high concentration (10 microliters of 50 mM NMDA in phosphate buffer, pH 7.4) into the rat cortex. Local injection of lactic acid and a minor stab wound in the cortex were used as a reference. The tissue damage was evaluated with immunohistochemical markers for neurons (MAP2, parvalbumin) and for astrocytes (GFAP and S100 protein). The stab wound and infusion of lactic acid led to a small distinct area of pan-necrosis with a sharp border to the surrounding tissue. The NMDA lesions were characterized by a center of pan-necrosis with loss of all tissue elements that were larger and less distinctly demarcated than the other lesions. This study shows that activation of NMDA receptors per se can induce pan-necrosis, and we conclude that the transition from selective neuronal necrosis to infarction depends on the intensity of the neuronal damage process.

Animals↗
PubMed1994

18F-labelled vesamicol derivatives: syntheses and preliminary in vivo small animal positron emission tomography evaluation.

As possible presynaptic tracers for cholinergic function in humans, three 18F-labelled vesamicol analogs were synthesized for use in positron emission tomography (PET): cis-[18F]-4-fluoromethylvesamicol (FMV), [18F]-N-fluoroacetamidobenzovesamicol (FAA) and [18F]-N-ethyl-N-fluoroacetamidobenzovesamicol (NEFA). Radiolabelling was accomplished using [18F]fluoride and the corresponding tosylates, the syntheses of which are also described. Yields were on the order of 40-60, 5 and 40-60%, respectively. Dynamic studies of the biodistribution in rats of [18F]FAA and [18F]NEFA using PET were compared with those previously reported for [18F]FMV. Due to probable rapid metabolism, [18F]FAA was considered unsuitable as a ligand for in vivo imaging. [18F]NEFA, similar to [18F]FAA, displayed a more moderate cerebral uptake than that of [18F]FMV (2 vs 20-30%). Pretreatment with vesamicol blocked the cerebral uptake, indicating a specific interaction with the vesamicol binding site. The biodistribution of high specific activity [18F]NEFA with time could be described with a three-compartmental model. The evaluation of [18F]NEFA as a tracer for cholinergic function is currently being pursued in monkeys and humans.

Animals↗
PubMed1994

Methodological aspects of brain activation studies: cerebral blood flow determined with [15O]butanol and positron emission tomography.

In this methodological study, a procedure for measuring regional CBF (rCBF) with positron emission tomography and 15O-labelled tracers is optimized. Four healthy volunteers were subjected to eight studies with use of [15O]butanol as a tracer: four times while reading aloud and four times while reading silently from a phonologically balanced list of single words. The gain from these repeated intra-individual studies of the same activation state (fractionation) was demonstrated in terms of noise-equivalent counts in a phantom study. A computerized brain atlas was used to reformat the images to a common anatomical representation, thereby minimizing the effects of inter- and intra-individual anatomical and positional variations. This allowed the formation of inter- and intra-individual average subtraction images with error estimates. Differences between the two activation states were detected with use of an exploratory significance map based on a paired Student's t test. The results compared well with Friston's method of determining levels of statistical significance. No difference was obtained when comparing results from rCBF images and images generated from measurement of uptake of the tracer. The paradigm chosen for activation was shown to yield a constant activation level during the repeated measurements (i.e., no habituation).

Brain↗
PubMed1994

Urge to scratch represented in the human cerebral cortex during itch.

1. We used functional positron emission tomography (PET), measuring regional cerebral blood flow (rCBF) as an index of neuronal activity, to investigate the central processing of itch in 10 healthy volunteers subjected to intracutaneous injections of histamine. 2. The study has unraveled a central representation that depicts a motor intention of the urge to scratch contingent on the perception of unpleasant itch. The coactivation of the anterior cingulate cortex (ACC), supplementary motor area (SMA), premotor area (PM), and inferior parietal lobule (IPL) substantiates that the posterior sector of the ACC (Brodmann 24) is related to the sensorial/affectional aspect of the event. The premotor cortical areas (SMA, PM) and the IPL may participate in the preparation of an intended action.

Adult↗
PubMed1993

Striatal D2/acetylcholine interactions: PET studies of the vesamicol receptor.

The regional cerebral distribution of [18F]NEFA, an aminobenzovesamicol (ABV), was studied in primates with PET. The binding was stereoselective and could be blocked but not displaced with vesamicol. The regional distribution pattern at late times, striatum > cortex > cerebellum, was corroborated by in vitro autoradiography using [3H]ABV and is consistent with known patterns of cholinergic innervation. Pretreatment with sigma 1 or D1 antagonists did not affect the striatal uptake, whereas D2 antagonists markedly augmented the uptake. This is consistent with the known induction of acetylcholine turnover in the striatum in response to D2-receptor blockade and demonstrates that the amount of [18F]-(-)-NEFA incorporated was influenced by the cholinergic activity in the target neurones.

Acetylcholine↗
PubMed1993

Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat.

Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.

Animals↗
PubMed1993

A one-step immunohistochemical method for detection of blood-brain barrier disturbances for immunoglobulins in lesioned rat brain with special reference to false-positive labelling in immunohistochemistry.

Disturbances of the blood-brain barrier (BBB) following brain lesions lead to extravasation of serum proteins that can be detected by immunohistochemical methods in tissue sections. Here, extravasated immunoglobulins were visualized by a 1-step technique using rabbit anti-rat immunoglobulins conjugated to horseradish peroxidase (HRP). This method is associated with a lower background staining than the conventional 3-step peroxidase-antiperoxidase (PAP) technique using rabbit antibodies against rat whole-serum proteins or immunoglobulins (IgG). Further tests using a direct conjugate of rabbit anti-rat immunoglobulins to fluorescein isothiocyanate (FITC) showed usefulness of the approach for fluorescence microscopy. Additional experiments showed that antibodies directed against mouse immunoglobulins as used for detection of mouse monoclonal antibodies can cross-react with extravasated rat immunoglobulins. Therefore, immunohistochemical studies on lesioned rat brain should routinely include a visualization of areas containing extravasated serum proteins including immunoglobulins.

Animals↗
PubMed1993

Synthesis of [1-11C]D-glucosamine and evaluation of its in vivo distribution in rat with PET.

D-Glucosamine is a structural unit of many biologically interesting macromolecules. To investigate the feasibility of using labelled D-glucosamine as a tracer for anabolic processes, a two-step synthetic procedure for specifically labelling D-glucosamine in position 1 with carbon-11 was developed. [11C]Cyanide was reacted with an imine precursor, N-benzyl-D-arabinosylamine, to generate the [1-11]alpha-amino nitrile. Reduction to [1-11C]D-glucosamine was accomplished by catalytic hydrogenation using PdCl2 and the N-benzyl group was simultaneously removed. The total synthesis time from end-of-trapping of [11C]cyanide was 40-45 min and the decay-corrected radiochemical yield was 5-10% after HPLC isolation. The biodistribution of [1-11C]D-glucosamine in rat following i.v. bolus injection was investigated using positron emission tomography and showed that the availability of this substance for CNS anabolism is low with the primary limitation being the intact blood-brain barrier.

Animals↗
PubMed1993

Comparison of [11C]flumazenil and [18F]FDG as PET markers of epileptic foci.

Recent PET results indicate that the benzodiazepine (BZ) receptor density measured with the BZ receptor antagonist [11C]flumazenil is reduced in human epileptic foci. The present study examines the applicability of this finding in the presurgical investigation of patients with intractable partial epilepsy. In eight patients, the PET measurements were performed after injection of the BZ receptor antagonist [11C]flumazenil and [2-18F]2-deoxy-2-fluoro-D-glucose ([18F]FDG)--a tracer for measurements of the rate of regional glucose metabolism. The focus localising ability of the two PET tracers was examined using extra--and intracranial EEG recordings as reference. The focus was first determined visually on the PET images obtained after a bolus injection of each of the PET tracers. Its anatomical localisation and spatial delimitation was then evaluated for each patient with a computerised anatomical brain atlas. [11C]flumazenil was found to be a more sensitive and accurate focus localiser than [18F]FDG. This observation was valid both for quantified and non-quantified images. In the preoperative diagnosis of epileptic foci, the PET measurements of BZ receptors may be a suitable and, in some cases, superior method to the generally used "[18F]FDG-PET" method.

Adult↗