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Astrogliosis in the cerebral cortex of gerbils after long-term exposure to 1,1,1-trichloroethane.

Mongolian gerbils (Meriones ungiculatus) were continuously exposed by inhalation to 1,1,1-trichloroethane at 70, 210, or 1 000 ppm for three months, followed by a four-month postexposure solvent-free period. Concentrations of two astroglial proteins, S-100 and glial fibrillary acidic (GFA) protein, were then determined in different regions of the cerebral cortex. The main biochemical alterations induced after exposure to 210 and 1 000 ppm of 1,1,1-trichloroethane demonstrated a pronounced change in gerbil brain; increased concentrations of GFA protein were found in the cerebral sensorimotor cortex at both these exposure levels, an occurrence indicating astrogliosis in this brain region. These results suggest that 1,1,1-trichloroethane should not be regarded as harmless, particularly regarding neurotoxicity, as previously claimed.

Animals↗

Proteomic analysis of the brain in Alzheimer's disease: molecular phenotype of a complex disease process.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for about 50% of all dementias, yet its pathogenic mechanisms remain poorly understood. In order to provide a more complete picture of pathogenesis in AD, we analysed six human brain regions for alterations in their proteomes. Quantitative proteome analysis was used to compare signals corresponding to individual proteins between post mortem brain tissues from persons with AD, and those from age-matched nondemented control (NC) tissues. In severely injured brain regions, 76 proteins were differentially expressed in AD hippocampus compared with NC, 62 proteins were differentially expressed in temporal cortex, and 39 proteins were differentially expressed in entorhinal cortex. Significant differences were also present in relatively spared regions. Thus, 34 proteins were differentially expressed in AD cerebellum compared with NC, 125 proteins were differentially expressed in cingulate gyrus, and 75 proteins were differentially expressed in sensorimotor cortex. The identity of 37 of these proteins was determined, and the possible relevance of changes in key pathogenic pathways analysed. These studies provide a unique snapshot illustrating the complexity of interrelated disease mechanisms at work in a complex, multifactorial disease, and show that comparative proteome analysis is a method with the power to develop important new insights into pathogenic mechanisms in the dementias.

Alzheimer Disease↗

Kainic acid-induced perirhinal cortical seizures in rats.

Seizures induced in rats by kainic acid microinjection into the perirhinal cortex were studied electrophysiologically and behaviorally and compared with known features of seizures following kainic acid injection into the amygdala. Unlike amygdalar seizures, perirhinal cortical seizures did not generalize to become limbic seizures but rather spread to sensorimotor cortex to become manifest as motor seizures. Perirhinal cortical seizures also required larger kainic acid doses for provocation and were briefer.

Amygdala↗

Involvement of motor cortices in retrieval of kanji studied by functional MRI.

Functional magnetic resonance imaging was successfully used to study the activation of the motor cortices during retrieval of Japanese ideogram, kanji. The subjects performed kanji completion tasks to generate a kanji in response to an element which is always written first. In most of the subjects, the contralateral premotor cortex, the presupplementary motor area (pre-SMA) and the bilateral intraparietal sulcus were activated during retrieval of kanji without actual writing nor intentional mental writing. Activation associated with actual writing was shown in the contralateral primary sensorimotor cortex and the SMA proper. These results suggested that retrieval of kanji would share the neural basis of motor representation with writing of kanji except for regions directly working for motor output.

Adult↗

Long-range focal collateralization of axons arising from corticocortical cells in monkey sensory-motor cortex.

Small extracellular injections of HRP were placed into a stratum of corticocortical axons situated immediately deep to area 3b of the monkey somatic sensory cortex. This stratum had previously been demonstrated to contain corticocortical fibers linking the cytoarchitectonic fields of the somatic sensory cortex to one another and certain of them to the motor cortex. This method resulted in extremely successful filling of pyramidal cells, their axons, collateral axon branches, and terminations in areas 3b, 1, and 2 posterior to the injection and in areas 3a and 4 anterior to it. The major finding was that cells with somata situated in any one of these fields and with principal axons traversing the injection site have long collaterals, primarily in layers III and V, which can extend throughout their own cytoarchitectonic field and into one or more other fields. In these fields they give off focused, columnlike concentrations of terminal boutons, which can be separated from one another by 800 micron or more. The anterogradely labeled, primary corticocortical fibers, traced forwards into areas 3a and 4, have virtually identical focal terminations. These findings indicate that interareal connectivity in the sensory-motor cortex can be effected by the axon branches of single cells rather than by separate groups of cells, and this may form a basis for the convergence of place and modality information on single cells in the sensorimotor cortex, a convergence that is not seen in the thalamic input to this cortex.

Animals↗

[The vestibular nuclei as the integration center of central and peripheral afferent projections].

Responses of individual vestibular units were recorded in cat following electrical stimulation of the cerebral cortex and peripheral nerves. Convergence of central and peripheral inputs were recorded from 28 out of 75 cells (37%), localized in the lateral vestibular nucleus. The most important inputs to vestibular neurons come from the areas of sensorimotor cortex and peripheral nerves concerned with the same limb. However, crossed effects were observed in a limited number of vestibular neurons.

Animals↗

Effect of unilateral motor cortex ablation on activity of choline acetyltransferase and levels of amino acid transmitter candidates in the spinal cord of adult monkeys.

Evidence that L-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function in discrete regions of spinal cord after ablation of sensorimotor cortex in monkeys. One and five weeks after unilateral cortical ablation, samples from six areas of spinal cord (ventral, lateral and dorsal regions of the left and right sides) were analysed for choline acetyltransferase (ChAT) activity and contents of amino acid transmitter candidates-glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA). During one to five weeks after unilateral cortical ablation of the monkey, prolonged hemiplegia in the contralateral side was observed. Histological examination of the spinal cord 5 weeks after unilateral (left) cortical ablation showed no apparent change in either control (ipsilateral, left) or affected (contralateral, right) sides of the cord as examined by the Klüver-Barrera method. The ChAT activity as a cholinergic marker was scarcely changed in any region of either left (control) or right (affected) side of the spinal cord at one and five weeks after unilateral (left side) ablation of the motor cortex. Amino acid levels in each region of the spinal cord were not significantly changed one week after unilateral ablation of the motor cortex. However, a significant decrease of Glu content was observed in the lateral column of the affected (right) side compared to the control (left) side of cervical and lumbar cord five weeks after cortical ablation of the left motor area. No concomitant alterations of other amino acids were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

[Changes in the dehydrogenase and GABA transaminase activity in the cerebral cortex during corazol kindling].

The experiments on (CBA X C57BL/6)F1 mice have shown that regular corazol injections in subliminal doses stimulated seizure susceptibility (pharmacological kindling). Cytophotometric assay of the activity of oxidative metabolism enzymes (glutamate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, alpha-oxoglutarate dehydrogenase, lactate dehydrogenase) and GABA-transaminase in the sensorimotor cortex of kindled mice in post-convulsive period, and 24 hours or 30 days after corazol injections were discontinued, has revealed some specific alterations of the enzymes under study, that suggest the existence of two phases of energy metabolism disturbances. The first phase (24 hours after corazol injections were discontinued) is characterized by intensified succinic acid oxidation, while the second phase (30 days after the last injection) is characterized by anaerobic glycolysis in neuronal and glial cells. Inhibition of GABA-transaminase activity was particularly marked in postconvulsive period. From a molecular point of view these data may be considered as enzyme disturbances during stimulation of seizure susceptability or seizure activity and as a compensation component ensuring anticonvulsive mechanisms and reparative processes (antagonistic principle of molecular mechanism regulation) during activation of antiepileptic system.

4-Aminobutyrate Transaminase↗

Distributed neuronal networks for encoding category-specific semantic information: the mismatch negativity to action words.

Mismatch negativity (MMN), an index of experience-dependent memory traces, was used to investigate the processing of action-related words in the human brain. Responses to auditorily presented movement-related English words were recorded in a non-attend odd-ball protocol using a high-density electroencephalographic (EEG) set-up. MMN was calculated using responses to the same words presented as standard and deviant stimuli in different sessions to avoid contamination from phonetic-acoustic differences. The topography of the mismatch negativity to action words revealed an unusual centro-posterior distribution of the responses, suggesting that activity was at least in part generated posterior to usually observed frontal MMNs. Moreover, responses to hand-related word stimulus (pick) had a more widespread lateral distribution, whereas leg-related stimulus (kick) elicited a more focal dorsal negativity. These differences, remarkably reminiscent of sensorimotor cortex topography, were further assessed using distributed source analysis of the EEG signal (L2 minimum-norm current estimates). The source analysis also confirmed differentially distributed activation for the two stimuli. We suggest that these results indicate activation of distributed neuronal assemblies that function as category-specific memory traces for words and may involve sensorimotor cortical structures for encoding action words.

Acoustic Stimulation↗

Epilepsia partialis continua. Epileptogenic focus in motor cortex and its participation in transcortical reflexes.

We performed electrophysiologic and neuroradiologic studies on a patient who had epilepsia partialis continua (EPC) to elucidate the pathophysiologic mechanism of repeated myoclonic jerks confined to the right toes. A computed tomographic scan revealed a small cortical lesion in the left parasagittal rolandic area corresponding to the sensorimotor cortex of the right toes. A pretrigger EEG analysis with a jerk-locked averaging technique revealed a positive spike 32 ms before the jerks. A similar positive spike was evoked at a latency of 48 ms after an electrical stimulation of the right posterior tibial nerve; it was followed by a myoclonic jerk with a 32-ms latency. We suppose that in our patient, an epileptogenic focus in the motor cortex and transcortical long-loop reflexes played an important role in generating EPC.

Adult↗

A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: implications for the neuropathology of schizophrenia.

BACKGROUND: As a test of plausibility for the hypothesis that schizophrenia can result from abnormal brain, especially cerebral cortical, development, these studies examined whether, in the rat, disruption of brain development initiated on embryonic day (E) 17, using the methylating agent methylazoxymethanol acetate (MAM), leads to a schizophrenia-relevant pattern of neural and behavioral pathology. Specifically, we tested whether this manipulation leads to disruptions of frontal and limbic corticostriatal circuit function, while producing schizophrenia-like, region-dependent reductions in gray matter in cortex and thalamus. METHODS: In offspring of rats administered MAM (22 mg/kg) on E17 or earlier (E15), regional size, neuron number and neuron density were determined in multiple brain regions. Spontaneous synaptic activity at prefrontal cortical (PFC) and ventral striatal (vSTR) neurons was recorded in vivio. Finally, cognitive and sensorimotor processes mediated by frontal and limbic corticostriatal circuits were assessed. RESULTS: Adult MAM-E17-exposed offspring showed selective histopathology: size reductions in mediodorsal thalamus, hippocampus, and parahippocampal, prefrontal, and occipital cortices, but not in sensory midbrain, cerebellum, or sensorimotor cortex. The prefrontal, perirhinal, and occipital cortices showed increased neuron density with no neuron loss. The histopathology was accompanied by a disruption of synaptically-driven "bistable membrane states" in PFC and vSTR neurons, and, at the behavioral level, cognitive inflexibility, orofacial dyskinesias, sensorimotor gating deficits and a post-pubertal-emerging hyper-responsiveness to amphetamine. Earlier embryonic MAM exposure led to microcephaly and a motor phenotype. CONCLUSIONS: The "MAM-E17" rodent models key aspects of neuropathology in circuits that are highly relevant to schizophrenia.

Amphetamine↗

Axonal plasticity is associated with motor recovery following amphetamine treatment combined with rehabilitation after brain injury in the adult rat.

Clinical and laboratory studies have suggested that amphetamine treatment when paired with rehabilitation results in improved recovery of function after stroke or traumatic brain injury. In the present study, we investigated whether new anatomical pathways developed in association with improved motor function after brain damage and amphetamine treatment linked with rehabilitation. Following a unilateral sensorimotor cortex lesion in the adult rat, amphetamine (2 mg/kg) was administered in conjunction with physiotherapy sessions on postoperative days two and five. Physiotherapy was continued twice daily for the first 3 weeks after injury, and then once daily until week six. Performance on skilled forelimb reaching and ladder rung walking was used to assess motor improvement. Our results show that animals with sensorimotor cortical lesions receiving amphetamine treatment linked with rehabilitation had significant improvement in both tasks. Neuroanatomical tracing of efferent pathways from the opposite, non-damaged cortex resulted in the novel finding that amphetamine treatment linked with rehabilitation, significantly increased axonal growth in the deafferented basilar pontine nuclei. These results support the notion that pharmacological interventions paired with rehabilitation can enhance neuronal plasticity and thereby improve functional recovery after CNS injury.

Amphetamine↗

Cortical origin of pathological pain.

Pain without accompanying tissue pathology poses a classic puzzle, presented in extreme form by phantom pain in a non-existent amputated limb. A clue to the origin of such pain is given by the recent discovery of a region of cortex active in response to incongruence between motor intention, awareness of movement, and visual feedback. Phantom-limb sensation, and repetitive strain injuries or focal hand dystonias in writers, musicians, or keyboard operators, are accompanied by plastic changes in sensorimotor cortex and by pathological pain. Disorganised or inappropriate cortical representation of proprioception may falsely signal incongruence between motor intention and movement, which results in pathological pain in the same way that incongruence between vestibular and visual sensation results in motion sickness.

Animals↗

Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation.

PURPOSE: Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of posttraumatic epilepsy. The involvement of iron-mediated oxygen free radical species and neuronal lipid peroxidation in iron-induced seizure has been suggested. Melatonin exerts free radical scavenging properties. In this study, we examined the protective effect of melatonin against iron-induced seizures. METHODS: We examined the protective effect of melatonin against in vitro iron-induced oxidative damage in homogenates from rat cerebral cortex, by measuring the concentration of thiobarbituric acid reactive substances (TBARS), as an index of oxidative damage. We also examined the effect of melatonin on the appearance of epileptic discharges in the EEG following injection of FeCl3 into the sensorimotor cortex in anesthetized rats, and by measuring the concentration of TBARS in the brain tissue. RESULTS: FeCl3 increased the concentration of TBARS in brain homogenates in a concentration-dependent manner, and melatonin reduced FeCl3-induced rise in TBARS in a dose-response fashion. Pretreatment with melatonin suppressed or delayed the development of FeCl3-induced epileptic discharges and decreased the concentration of TBARS in brain tissues. CONCLUSIONS: Our results suggest that iron ion generates oxygen free radical species that induce neuronal macromolecular peroxidation and seizure, and that melatonin inhibits iron-induced seizures by scavenging free radicals.

Animals↗

Correlation of motor cortex brain mapping data with magnetic resonance imaging.

Brain maps derived intraoperatively from patients undergoing tumor resection were correlated retrospectively with magnetic resonance (MR) images with respect to the precise localization of the motor cortex in an attempt to identify useful preoperative MR imaging landmarks that correspond to functional brain regions. Superior axial T2-weighted MR images consistently localized the central sulcus, whereas parasagittal and farlateral sagittal images readily identified the rolandic (sensorimotor) cortex, as a functional unit, based on the cingulate-marginal sulcus and insula, respectively. It is therefore concluded that multiplanar MR images may serve as a useful preoperative planning aid prior to removing intrinsic brain tumors within or adjacent to the motor cortex.

Brain Mapping↗

Synchronization between motor cortex and spinal motoneuronal pool during the performance of a maintained motor task in man.

1. Simultaneous recordings of cortical activity, recorded as the magnetoencephalogram (MEG), and the electromyogram (EMG) of the ipsilateral and contralateral first dorsal interosseous muscles (1DI) were made during maintained voluntary contractions. 2. The MEG recorded from a localized region of the sensorimotor cortex of the dominant hemisphere was coherent with the EMG from the contralateral 1DI muscle over a limited band of frequencies. The peak coherence was confined largely within the beta range of cortical activity (13-35 Hz). Significant cortical activity at 10 Hz and 40-50 Hz was not correlated with motor output. The MEG and EMG from the ipsilateral 1DI muscle were uncorrelated at all frequencies. 3. Significant coherence between the MEG and the EMG was associated with synchronous behaviour between the MEG and EMG in the time domain. 4. The results demonstrate that synchronized cortical activity contributing to MEG activity within the beta range of frequencies during maintained voluntary contractions is coupled to motor output at frequencies of motor-unit activity associated with motor-unit synchronization. This observation provides further evidence for the involvement of cortical neurones in the generation of motor-unit synchronization. 5. We suggest that the coherence between MEG and contralateral EMG observed during maintained isometric contractions may provide an example of binding within the motor system.

Adult↗

[Cytophotometric study of changes in glutamate dehydrogenase and GABA transaminase in the cerebral cortex during corazole kindling].

It has been demonstrated in (CBA X C57BL/6) F1 mice that daily corazole injections (30 mg/kg) lead to the development of pharmacological kindling that manifests in a progressive increase of seizure susceptibility, seizure occurrence in response to the subthreshold convulsant dose and in demonstrable seizures. Cytophotometric study of the histological specimens of the sensorimotor cortex discovered the reduced enzymatic activity of glutamate dehydrogenase and GABA transaminase in the neurons. In the neuroglial cells, the activity of glutamate dehydrogenase also declined, whereas that of GABA transaminase tended on the contrary, towards increase.

4-Aminobutyrate Transaminase↗

Temporal dynamics of parietal cortex involvement in visual search.

The functional-neuroanatomic relationship that describes the involvement of the parietal cortex in visual search was investigated using repetitive transcranial magnetic stimulation (rTMS; 10 Hz, 500 ms in duration). Twelve adult participants performed feature-based visual search for a unique letter-without eye movements-under conditions that involved manipulations of search efficiency (efficient versus inefficient) and target-selection demands (set-size: 4 versus 10). rTMS was applied over the right posterior parietal cortex at the onset of the search array for all factorial conditions (0-500 ms); stimulation was additionally administered at 500 ms post-array onset (500-1000 ms) during inefficient search (set-size 10). Stimulation over the primary sensorimotor cortex served as a within-subjects control condition, and eye movements were monitored continuously. Significant increases in reaction time were restricted to parietal stimulation during inefficient search (set-size 10), with interference observed when rTMS was administered at the onset of the search array and at 500 ms post-array onset. The early effect was confined to target-present trials and the late effect was confined to target-absent trials, which may indicate temporally dissociable parietal involvement in target detection and response-based selection and/or search termination, respectively. Error rates did not vary significantly as a function of any of the independent variables. Taken together, these results are consistent with evidence from functional magnetic resonance studies indicating that inefficient feature-based visual search requires an intact parietal cortex, and also indicate that the parietal cortex is involved in inefficient search later than has been previously reported.

Adult↗