Search PubMed⌕ Search

Biomedical subjects

K Mewes

Publications and source records attributed to K Mewes.

At least 19 recordsLinked to original sources
PubMed2001

The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.

Single-cell recording of the subthalamic nucleus (STN) was undertaken in 14 patients with Parkinson's disease submitted to surgery. Three hundred and fifty neurones were recorded and assessed for their response to passive and active movements. Thirty-two per cent were activated by passive and active movement of the limbs, oromandibular region and abdominal wall. All neurones with sensorimotor responses were in the dorsolateral region of the STN. Arm-related neurones were lateral (> or =14 mm plane) to leg-related neurones, which were found more medially (< or =12 mm). Representation of the oromandibular musculature was in the middle of the sensorimotor region (approximately 13 mm plane) and ventral to the arm and leg. Two hundred neurones were adequately isolated for 'off-line' analysis. The mean frequency of discharge was 33 +/- 17 Hz (13-117 Hz). Three types of neuronal discharges were distinguished: irregular (60.5%), tonic (24%) and oscillatory (15.5 %). They were statistically differentiated on the basis of their mean firing frequency and the coefficient of variation of the interspike interval. Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded. The majority (84%) of these were sensitive to movement and were located in the dorsolateral region of the STN. Cross power analysis (n = 16) between the rhythmic neuronal activity and tremor in the limbs showed a peak frequency of 5 Hz (4-8 Hz). Neuronal activity of the substantia nigra pars reticulata was recorded 0.5-3 mm below the STN. Eighty neurones were recorded 'on-line' and 27 were isolated for 'off-line' analysis. A tonic pattern of discharge characterized by a mean firing rate of 71 +/- 28 Hz (35-122 Hz) with a mean coefficient of variation of the interspike interval of 0.85 +/- 0.29 ms was found. In only three neurones (11%) was there a response to sensorimotor stimulation. The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys.

Action Potentials↗
PubMed1999

Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus.

Microelectrode recording was performed in the basal ganglia of 3 patients with generalized dystonia and 1 patient with hemiballismus secondary to a brainstem hemorrhage. Neuronal activity was recorded from the internal and external segments of the globus pallidus and assessed for mean discharge rate and pattern of spontaneous activity. The responses of neurons in the internal segment of the globus pallidus to passive and active movements were also evaluated. Mean discharge rates of neurons in both segments of the pallidum in patients with dystonia and the patient with hemiballismus were considerably lower than those reported for patients with idiopathic Parkinson's disease. In addition, the pattern of spontaneous neuronal activity was highly irregular, occurring in intermittent grouped discharges separated by periods of pauses. Although receptive fields in the dystonia patients were widened and less specific than those reported in normal monkeys, neuronal responses to movement were uncommon in the hemiballismus patient. Before surgery, patients with dystonia experienced abnormal posturing and involuntary movements. Coactivation of agonist-antagonist muscle groups was observed both at rest and during the performance of simple movements. After pallidotomy there was a significant reduction in the involuntary movement associated with these disorders and a more normal pattern of electromyographic activity during rest and movement. Given the improvement in dystonic and hemiballistic movements in these patients after ablation of the sensorimotor portion of the internal segment of the globus pallidus, we suggest that pallidotomy can be an effective treatment for patients with dystonia and also for patients with medically intractable hemiballismus. Based on the finding of decreased neuronal discharge rates in pallidal neurons, we propose that physiologically dystonia most closely resembles a hyperkinetic movement disorder. A model for dystonia is proposed that incorporates the observed changes in the rate and pattern of neuronal activity in the pallidum with data from neuroimaging with positron emission tomography and 2-deoxyglucose studies.

Adult↗
PubMed1998

The subthalamic nucleus and tremor in Parkinson's disease.

The role of the subthalamic nucleus (STN) in the origin of parkinsonian tremor is discussed. Previous studies in monkeys made parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration suggested a direct participation of the STN in the pathophysiology of tremor. We recorded tremor-related activity in the STN in 12 patients with Parkinson's disease (PD) and found that microstimulation of the sensorimotor region of the nucleus, where these neurons are present, stopped the tremor with a very short latency. Long-term treatment by means of bilateral deep-brain stimulation (DBS) in the same 12 patients led to a significant reduction of tremor as well as other cardinal features of PD. This effect was blindly assessed at 3 months after implantation. In another group of seven patients, a unilateral lesion of the STN was performed. Both postural and resting tremor were significantly improved on the limbs contralateral to the lesion side. In three patients, tremor disappeared completely after 12 months of follow up. The electrophysiologic data and therapeutic effect of inactivating the STN strongly indicated that this structure is directly involved in the origin of parkinsonian tremor, as suggested by the MPTP model.

Adult↗
PubMed1998

Visual fields in patients with posterior GPi pallidotomy.

The objective of this study was to describe the incidence and types of visual field defects after posterior globus pallidus internus (GPi) pallidotomy for Parkinson's disease. The creation of the pallidotomy lesion carries a risk of damaging neighboring structures such as the optic tract. The reported frequency of visual field defects in patients after pallidotomy varies from 0 to 40%. Goldmann visual field testing was performed on 40 patients who underwent microelectrode-guided posterior GPi pallidotomy. The optic tract was identified during the procedure by listening during microelectrode recording for the evoked responses to light flashes and by assessing stimulation-induced subjective responses. After the first 18 patients, lesioning thresholds were increased from 0.5 to > or =1.0 mA so that the lesion was placed more distant from the optic tract. The location of individual lesions was determined on postsurgical MRI. Three patients (7.5%) had visual field defects likely related to the pallidotomy. These were contralateral homonymous superior quadrantanopias, associated in two patients with small paracentral scotomas. The incidence of visual field defects with the early technique was 11% (2/18) and decreased to 4.5% (1/22) after thresholds for lesioning were increased. Except for the location of the lesion relative to the optic tract (more ventral, adjacent to or extending into the optic tract), no other variable correlated with a post-pallidotomy visual field defect. Microelectrode-guided GPi pallidotomy is a relatively safe procedure as regards visual function even when the optic tract is used as a guide for lesion placement.

Adult↗
PubMed1998

Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson's disease.

OBJECT: The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy. METHODS: Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by "form fitting" the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies. CONCLUSIONS: These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

Antiparkinson Agents↗
PubMed1994

Enrichment of bovine X and Y spermatozoa by free-flow electrophoresis.

Conditions of separation of bovine spermatozoa according to their differences in electrophoretic mobility were studied using free-flow electrophoresis. Distribution of spermatozoa in the electric field depends on composition of buffer system, field intensities and temperature. Conditions are described for reproducible separation of anodically migrating spermatozoa into two distinct peaks both for cold-immobilized (10-13 degrees C) and for motile cells (25 degrees C). Electrophoresis with the buffer used at 25 degrees C and field intensities of 70-100 V/cm provided high percentages of motile spermatozoa (50-90%) in all fractions. However, the sperm distribution across the fractions was the result of superimposed passive electrophoretic motion towards the anode and the active galvanotactic migration towards the cathode. Separation of X- and Y-spermatozoa was verified by quantification of Y-spermatozoa by means of both in situ hybridization, using Y-specific DNA fragments, and the Y-specific fluorescence staining (f-body test). Y-spermatozoa could be enriched in anodic fractions (112 and 144% relative to control). X-spermatozoa were enriched in cathodic fractions (80 and 68% Y-spermatozoa, as compared to control).

Animals↗
PubMed1994

Primate rubromotoneuronal cells: parametric relations and contribution to wrist movement.

1. Fifty-nine rubromotoneuronal (RM) cells were identified in two rhesus monkeys on the basis of their postspike facilitation (PSpF) of rectified electromyographic (EMG) activity. These cells were studied in relation to a step tracking task requiring wrist movements between fixed target zones in flexion and extension. Movement away from a 0 position was opposed by spring-like loads (auxotonic). Additionally, nine cells were evaluated using an isometric task. Neuronal discharge could be divided into three basic components: background discharge in the absence of movement, phasic modulation during movement, and tonic modulation during sustained holding against external loads. 2. Four basic patterns of RM cell activity were observed in relation to ramp-and-hold wrist movements: phasic-tonic (44%), pure phasic (22%), pure tonic (2%), and unmodulated (24%). The discharge of unmodulated cells did not covary with movement parameters but, as with other RM cells, background discharge did increase in association with task performance. 3. The phasic discharge of RM cells led to the onset of target muscle EMG activity by an average of 89 +/- 82 ms (mean +/- SD, n = 104) in extensors and 88 +/- 74 ms (n = 30) in flexors. Target muscles are defined as ones showing PSpF of EMG activity. It was found that 94% of extensor and 87% of flexor RM cells discharged before or synchronous with the onset of target muscle EMG activity. 4. Thirty-one RM cells (53%) showed a tonic increase in cell activity during the static hold phase of the task. Twenty-three of these were tested for relations to static torque. Fifteen extension related cells and one flexion cell had significant, positive regression slopes for the relation between tonic discharge rate and static torque. The mean rate-torque slope for extension related cells was 160 Hz/Nm and 103 Hz/Nm for flexion related cells. These mean slopes are about one-third those of corticomotoneuronal (CM) cells. 5. Cell discharge rate was correlated with velocity and rate of change of torque (dT/dt) for 32 RM cells with a phasic component of discharge during movement. The peak increase in phasic discharge above tonic firing rate (PDI, peak dynamic index) was significantly correlated only with velocity in eight cells and only with dT/dt in five cells. The phasic discharge of four additional cells was correlated with both velocity and dT/dt, but for three of these cells, the correlation was stronger for velocity. The mean slope for the relation between velocity and PDI was 0.31 Hz.deg-1.s-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Synthesis and structural elucidation of biliary excreted thioether derivatives of mitoxantrone.

1. Hplc-MS coupling has been used for the identification of thioether derivatives of the anticancer agent mitoxantrone in the bile of pig. 2. Three biologically relevant new thioether derivatives of mitoxantrone have been synthesized by a horseradish peroxidase-catalysed reaction. 3. The thioether derivatives have been characterized by means of ion-spray tandem mass spectrometry and nmr spectrometry including two-dimensional techniques. 4. The carbon-sulphur bond formation takes place at the hydroquinone moiety of the anthraquinone skeleton pointing to the importance of a tautomeric equilibrium between different species of the oxidized drug. 5. The occurrence of the synthesized compounds in biological systems suggests a metabolic pathway that may be relevant for the cytotoxicity of mitoxantrone (oxidative activation).

Animals↗
PubMed1994

Busulfan pharmacokinetics in bone marrow transplant patients: is drug monitoring warranted?

Pharmacokinetics were studied in relation to hepatic side-effects in 20 patients (19 adults aged 18-53 years and one child of 11 years) undergoing BMT after conditioning with 1 mg/kg busulfan (every 6 hours for 16 doses). Busulfan was quantitated in plasma samples at 10 time points within the 6 h dosing interval using HPLC before and after dose numbers 1, 2, 5, 13 and 14. For 13 patients data on all five doses are available; for the remaining seven patients three to four doses were studied. Mean maximum concentrations were 1512 ng/ml; mean trough levels for second and subsequent doses were 615 ng/ml. Maxima (Cmax) tended to be lower and times of maxima (Tmax) were later when busulfan was taken with a meal. Correlation of the area under the concentration versus time curve (AUC0-6h) between different doses was low within patients. In several patients problems with compartmental fitting of concentration data were observed mainly caused by the short dosing interval, which made estimates of T1/2 and model derived AUCs unstable. Three patients experienced hepatic veno-occlusive disease; kinetic parameters were not helpful in describing a particulate risk constellation for this subgroup. In our experience, the role of drug monitoring in this setting needs to be defined more clearly.

Adolescent↗
PubMed1993

Cytochrome P-450-induced cytotoxicity of mitoxantrone by formation of electrophilic intermediates.

Recent studies of our group have shown that the oxidation of the substituted anthraquinone skeleton is involved in the biotransformation of mitoxantrone. In this report the importance of this process with regard to the mode of action of the drug is investigated. This communication describes a new high performance liquid chromatography separation for mitoxantrone and its metabolites allowing the direct coupling of high performance liquid chromatography to mass spectrometry. Application of this technique to bile of mitoxantrone-treated pigs reveals the formation of several metabolites in addition to the drug-derived compounds found in urine. Seven biliary metabolites are identified as thioether derivatives of mitoxantrone and its side chain oxidation products. Independent synthesis and structural elucidation of 3 thioether conjugates of the drug provides unequivocal evidence that the hydroquinone moiety of mitoxantrone is the site of reaction with glutathione. Furthermore, the formation of the thioether conjugates in HepG2 hepatoma cells and in rat hepatocytes during cell incubations is demonstrated. Inhibition of cytochrome P-450 with metyrapone prevents the formation of the thioether conjugates and leads to a complete loss of the cytotoxicity of mitoxantrone in HepG2 cells and rat hepatocytes up to concentrations of 200 to 400 microM thereby indicating that mitoxantrone has a negligible effect by itself. Rat hepatocytes were found to be more susceptible for the oxidation-induced cytotoxicity than HepG2 cells. These results demonstrate that the acute cytotoxicity of mitoxantrone depends on prior oxidation of its 1,4-dihydroxy-5,8-diaminoanthraquinone moiety.

Animals↗
PubMed1991

Isolation and structure elucidation of urinary metabolites of mitoxantrone.

Three 13C-labeled 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]-ethyl)amino-9,10- anthracenedione dihydrochloride (mitoxantrone) isotopomers were synthesized to prove the proposed chemical structures of human urinary metabolites by means of nuclear magnetic resonance spectroscopy. After application of labeled mitoxantrone to an anesthetized pig, urine was collected by way of a vesicourethral catheter. The urinary metabolites were isolated by liquid chromatography using a new procedure developed for extraction of mitoxantrone metabolites. Structural elucidation by nuclear magnetic resonance spectroscopy and tandem mass spectrometry confirmed the proposed mono- and dicarboxylic acid structures of the metabolites. High-performance liquid chromatography of native pig urine showed an additional metabolite detected by its UV-visible absorption. The new metabolite was identified as a glucuronic acid conjugate of mitoxantrone by means of nuclear magnetic resonance spectroscopy and tandem mass spectrometry. Incubation with beta-glucuronidase under high-performance liquid chromatography control revealed mitoxantrone as the sole product. Quantitative high-performance liquid chromatography analyses showed that the new urinary metabolite represents the main biotransformational pathway of mitoxantrone in pigs, indicating significant interspecies variation in mitoxantrone biotransformation. Expressed in equivalents of mitoxantrone, the new metabolite amounts to 25% and 31%, respectively, of urinary excreted drug-related material. Extraction of patient urine using the same procedure led to the isolation of pure metabolite B. Tandem mass spectrometric data delivered definitive evidence for the structure of metabolite B as monocarboxylic acid of mitoxantrone.

Animals↗
PubMed1991

Facilitation and suppression of wrist and digit muscles from single rubromotoneuronal cells in the awake monkey.

1. The output effects of 214 cells in the magnocellular red nuclei of two rhesus monkeys (Macaca mulatta) were tested with spike-triggered averaging of electromyogram (EMG) activity from six forearm extensor and six flexor muscles. The monkeys performed an alternating wrist movement task (auxotonic paradigm) or generated wrist torque trajectories alternating between flexion and extension (isometric paradigm). 2. Sixty-five cells (30%) were identified as rubromotoneuronal (RM) cells on the basis of their postpike effects on forearm flexor and extensor muscles. Three major types of RM cell output organization were identified: 1) pure facilitation (28 cells), 2) reciprocal (18 cells), and 3) cofacilitation (16 cells). 3. RM cell output showed a strong preference for facilitation of extensor forearm muscles. This preference was reflected in the fact that 69% (43 of 62) of RM cells facilitated extensors exclusively or most strongly; 27% facilitated flexors exclusively or most strongly; and 5% facilitated flexors and extensors equally. Postspike facilitation (PSpF) was observed in 45% of the extensor muscles and 20% of the flexors tested. In contrast, postpike suppression (PSpS) was observed in 3% of the extensors and 7% of the flexors. 4. The mean number of extensors facilitated per RM cell was 3.1 (53% of tested) compared with 2.8 (51% of tested) flexors facilitated per cell. The extensor and flexor PSpS muscle field sizes were both 2.0 (35% of extensors and 36% of flexors tested). The mean number of muscles facilitated by cofacilitation cells was 5.8 (48%) per cell. No clear preference was found for facilitation of particular combinations of synergist muscles. 5. PSpF magnitude was assessed by measuring both the percent change of facilitation or suppression from baseline and the signal-to-noise ratio of effects. The overall average magnitudes of RM PSpF and PSpS were 4.1 +/- 2.0 and 4.0 +/- 2.3% change from baseline, respectively. The average magnitude of PSpF in flexors was not significantly different from that of extensors; neither was there a difference in the average magnitude of PSpS in flexors and extensors. 6. The mean onset latency of RM cell PSpS was greater than PSpF (9.2 +/- 3.0 vs. 5.7 +/- 1.8 ms; P less than or equal to 0.05). This can be attributed to an underlying minimal disynaptic linkage to motoneurons for suppression effects, whereas most PSpFs are probably mediated by underlying monosynaptic connections. The mean onset latency of flexor PSpFs was greater than that of extensors (6.4 +/- 2.3 vs. 5.4 +/- 1.5 ms; P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effects on wrist and digit muscle activity from microstimuli applied at the sites of rubromotoneuronal cells in primates.

1. The purpose of this study was to use the techniques of spike- and stimulus-triggered averaging (SpTA and StTA, respectively) to examine the output organization of individual rubromotoneuronal (RM) cells in relation to clusters of neighboring cells. SpTA of electromyographic (EMG) activity in awake monkeys reveals the target muscles of an individual recorded neuron, whereas StTA reveals the target muscles of the neuronal aggregate activated by the stimulus. 2. Three questions were of particular interest. First, does the pattern of poststimulus facilitation (PStF) across forearm muscles match the pattern of postspike facilitation (PSpF)? Second, does the output of RM cell aggregates tested with StTA favor forearm extensor muscles, as reported for individual RM cells in the companion paper? Third, how do RM poststimulus effects compare with corticomotoneuronal (CM) poststimulus effects? 3. Microstimuli were applied at the sites of 37 RM cells, identified by SpTA of EMG activity in awake monkeys performing an alternating wrist movement task. 4. The magnitudes of PStF at 5, 10, and 20 microA were, respectively, 4.3, 10.1, and 13.7 times greater than PSpF of the same muscles, reflecting activation, by the stimulus, of multiple RM cells. RM cell PStF was weaker than CM PStF. 5. The onset latency of poststimulus suppression (PStS) exceeded that of PStF. For example, at 20 microA the difference was 2.6 ms, comparable with the difference between PSpF and postspike suppression (PSpS). 6. The patterns of poststimulus effects on forearm flexor and extensor muscles were categorized in the same manner as postspike effects. Three major patterns were observed: 1) pure facilitation, 2) reciprocal suppression, and 3) cofacilitation of extensors and flexors. 7. The profile of PStF across synergist muscles was broadly similar to that of PSpF. At 83% of sites, the muscle with the greatest PSpF was also the muscle with the greatest PStF. At 30% of sites (11 of 37), the set of muscles with PStF (muscle field) exactly matched the set with PSpF. Overall, the level of discrepancies in SpTAs versus StTAs computed at the same RM cell sites was 27%. Most of these discrepancies could be attributed to muscles with the weakest effects. 8. The fact that the poststimulus muscle fields at many RM cell sites matched the postspike fields at the same sites, even though the poststimulus effects were greater in magnitude and were mediated by more cells, suggests clustering of RM cells with similar target motoneuron pools.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Control of forelimb muscle activity by populations of corticomotoneuronal and rubromotoneuronal cells.

We review and synthesize evidence on the activity of corticomotoneuronal (CM) and rubromotoneuronal (RM) cells and single motor units in forearm muscles in monkeys performing alternating wrist movements. The CM and RM cells were identified by post-spike facilitation of rectified forelimb EMG activity. RM cells facilitated more muscles per cell (mean: 3.0 of 6 synergist muscles) than CM cells (2.4/6). Both groups had "reciprocal" cells which also suppressed antagonists of their facilitated target muscles. Unlike CM cells, some RM cells cofacilitated flexor and extensor muscles (5.8 or 12 muscles). During performance of a standard ramp-and-hold force tracking task the firing patterns of CM and RM cells, as well as single motor units, fell into distinct response types. Each population had phasic-tonic and tonic cells. Unique to the CM population were cells whose discharge increased during the static hold period; unique to RM cells were bidirectionally responsive and unmodulated neurons. Many motor units showed decrementing discharge. To estimate the ensemble activities of these populations the response histograms of different cells were summed (with force ramps aligned) in proportion to the relative frequency of each cell type. The population response histogram of CM cells was phasic-tonic, consistent with the predominant response type. The population response of RM cells was also phasic-tonic, but showed a shallower phasic modulation relative to discharge that was sustained during both directions of movement. The population histogram of motor units of a muscle was proportional to the average of rectified multiunit EMG, and typically exhibited decrementing activity during the static hold. The effects of excitatory postsynaptic potentials (EPSPs) on firing probability of motoneurons previously documented in intracellular studies are combined with the mean firing rates in the population histograms and the known amplitudes of CM-EPSPs and RM-EPSPs to infer the relative contributions of the supraspinal cells to tonic discharge of active motoneurons. This analysis suggests that for intermediate levels of force, the CM cells would increment motoneuron discharge by about 9 impulses/second (i.p.s.) and RM cells by about 2.4 i.p.s. The analysis also reveals differences in the population activity of CM and RM cells compared to their target motoneurons, which may be due to other input cells and to recruitment properties of motoneurons.

Animals↗
PubMed1985

Implementation of a movement paradigm using the Commodore 64 microcomputer.

Implementation of an alternating movement paradigm for monkeys was achieved using an inexpensive but versatile microcomputer, the Commodore 64. During task performance, the computer monitors one of three user selectable input signals (e.g. joint position) and continuously displays this signal as a moving cursor on a video monitor along with a user positioned target box. Other user defined parameters include in-target holding time and reinforcement ratio. The system also provides two sound cues to signal entry of the cursor into the target box and successful completion of a trial. Extensive use is made of the computer's intrinsic hardware features for implementation of movement paradigm functions. Use of external components is limited to digitizing and interface hardware. A two part software package consisting of a BASIC and a machine language program performs all task and hardware related functions. Acquisition and display of analog input signals, display of target positions, and delivery of auditory cues and applesauce rewards are all controlled by the machine language program. All user defined parameters are specified from the BASIC menu program. The specific programs described in this paper should be applicable to the control of tasks requiring alternation of a behavioral parameter between two target zones.

Animals↗
PubMed1984

Soman induced changes in brain regional glucose use.

Soman, a potent central acetylcholine esterase inhibitor, has a greater impact on brain regional glucose use than other organophosphates, such as diisopropylfluorophosphate (DFP) or phospholinium iodide. At near-lethal doses soman induced explosive persistent seizures that were associated with a greater than fourfold increase of glucose use in many brain structures. Single near-lethal doses of soman lead to conspicuous neuronal damage and a marked reduction in brain activity, 1 to 3 days after exposure. When soman (2 X LD50) was given to TAB (an antidotal mixture of trimedoxime, atropine, and benactyzine ) pretreated rats, there was a greater than twofold reduction of glucose use in almost every brain region. We suggest that soman seizures are mediated via activation of muscarinic receptors; also, the substantia nigra has a key role in the initiation/propagation of seizures. Soman has in addition, a depressive effect on some brain components which appears not to involve muscarinic receptors. We suggest that the conspicuous pathology that follows a single, near-lethal dose of soman results from a depletion of energy flow along with an influx of Ca2+ which sets into motion a cascade of destructive reactions, such as activation of proteases.

Animals↗