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Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates.

This study characterizes physiological, histological and behavioral effects of traumatic brain injury (TBI) produced by a controlled pneumatic impactor striking the entire right sensorimotor cortex of the anesthetized rat. Damage to both the fore- and hindlimb sensorimotor areas resulted in a hemiparetic animal which allowed us to use four sensitive behavioral/neurological tests to track the recovery sequelae after injury. Initial experiments measured cardiovascular and respiratory effects after cortical impact which depressed the dura to varying depths. Both 0.5 mm and 1 mm cortical depressions produced a momentary decrease (P < 0.05) in mean arterial blood pressure (MABP) while cortical impacts to depths of 2 mm or 3 mm produced a momentary increase (P < 0.05) in MABP. Normotension was re-established within 30 s after the initial response at all injury levels. Respiratory rate was affected only following 3 mm cortical depressions. A 1 mm cortical depression appeared ideal in terms of minimal cardiorespiratory effects, low mortality and lasting behavioral effects. For behavioral and histologic studies, therefore, additional rats were injured by a 1 mm cortical impact and tested for 8 weeks after TBI using four behavioral tests. Injured rats displayed both fore- and hindlimb deficits up to 56 days while traversing a narrow beam (P < 0.001) and up to 28 days when crossing a pegged beam (P < 0.05). Forelimb deficits evaluated on a wire grid platform were evident for 28 days (P < 0.05). Forepaw preference measured in a non-test setting indicated a bias to use the unaffected forepaw for 35 days (P < 0.05). A biphasic pattern of functional recovery was seen on all tests. A period of rapid functional recovery lasting 7 to 10 days was followed by a slower period of functional recovery lasting many weeks. Possible meanings of this biphasic recovery are discussed as issues of behavioral compensation/adaptation versus true neural recovery. Eight weeks after TBI histological analyses indicated that axonal degeneration was present in the areas adjacent to the ipsilateral cortical injury site. Degenerating fibers also extended across the corpus callosum into the homologous area in the contralateral cortex and were seen in the ipsilateral striatum, somatosensory and motor thalamic nuclei and substantia nigra. Significant axonal degeneration occurred bilaterally around the deep cerebellar nuclei. Degenerating fibers extended into the folia and terminated in the cerebellar granule cell layer. Thus the entire sensorimotor control system appeared to have been affected by a cortical injury.

Animals↗

BOLD functional MRI may overlook activation areas in the damaged brain.

Clinical applications of blood-oxygenation-level-dependent contrast functional MRI (BOLD-fMRI) have been rapidly moving toward routine non-invasive cortical mapping in the patients with brain disorders. However, it is not yet clear whether the damaged brain shows same cerebral blood oxygenation (CBO) changes during neuronal activation as those in the normal adult. We compared the activation mapping obtained by BOLD-fMRI and the evoked-CBO changes measured by near infrared spectroscopy (NIRS) in normal adults (6 cases) and patients with damaged brain (6 cases of cerebral ischemia and 10 cases of brain tumors in or adjacent to the motor cortex). BOLD-fMRI demonstrated robust activation areas in the primary sensorimotor cortex (PSMC) during contralateral hand grasping tasks in all of the normal adults; however, in the cerebral ischemia (6 cases) and the brain tumors (2 cases), BOLD-fMRI demonstrated only limited activation areas in the PSMC on the lesion side during the task. NIRS demonstrated an increase of focal concentration of oxyhemoglobin and total hemoglobin at the PSMC during the task in all of the normal adults and the patients, indicating the presence of rCBF increase in response to neuronal activation. A focal concentration of deoxyhemoglobin decreased during the task in the normal adults, however, in the patients that showed limited activation areas by BOLD-fMRI, deoxyhemoglobin concentrations increased during the entire course of the task. In summary, the evoked-CBO changes occurring in the damaged brain differed from those in the normal brain. This indicates that BOLD-fMRI may overlook activation areas in the damaged brain.

Brain Ischemia↗

Spatial and cortical influences exerted on cuneothalamic and thalamocortical neurons of the cat.

This work aimed to study the responses of cuneothalamic and thalamocortical cells to electrical stimulation of the body surface in alpha-chloralose-anaesthetized cats. It was found that both classes of cells had a central excitatory receptive field, an edge overlapping the field centre whose stimulation elicited inhibitory-excitatory (cuneothalamic cells) and excitatory-inhibitory (thalamocortical cells) sequences, and a surrounding or peripheral area usually being inhibitory. Manipulating the descending corticofugal activity by removing the fronto-parietal cortex, electrical stimulation, or by placing picrotoxin or muscimol over the sensorimotor cortex demonstrated that the cortical feedback potentiated effects driven from the field centre and the surround. In particular this potentiated centre-driven excitation and surround-driven inhibition, but some of the data points to more complex patterns. The inhibition elicited in cuneothalamic cells from the edge and the surround of the field was faster than the excitation induced from the field centre. Effects at the edge of the field centre included late excitatory responses relayed via the cerebral cortex. There were also direct corticofugal excitatory inputs to the field centre. Excitatory surrounds were occasionally observed, the assumption being that in most cases these were suppressed by the enhanced inhibition driven from the cortex. The data indicate that the cortico-subcortical feedback contributes not only to enhance the surround antagonism of a centre response but also to increase the time resolution of thalamic and cuneate relay somesthetic neurons.

Action Potentials↗

Noradrenaline-sensitive cyclic AMP-generating system of rat cerebral cortex with iron-induced epileptiform activity.

Noradrenaline-elicited accumulation of cyclic AMP and effects of an alpha-, beta-adrenoceptor, or adenosine receptor antagonist on the accumulation were examined in slices of different areas of rat cerebral cortex in which ferrous chloride solution was injected unilaterally into the sensorimotor cortex to induce epileptiform activity. The cyclic AMP accumulation was altered regionally in relation to both lateral dominance of electrographic isolated spike activity and variance of the epileptic process. Involvement of a beta-adrenergic, and possibly alpha-adrenergic, mechanism in the alterations in the cyclic AMP accumulation was indicated.

Adrenergic alpha-Antagonists↗

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex.

The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed. The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image, and the image data set was then implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyrus were identified by neuronavigation, and in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the method. The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to cause less morbidity around eloquent brain areas.

Journal Article↗

Undershoots following stimulus-induced rises of extracellular potassium concentration in cerebral cortex of cat.

Extracellular potassium activity (ak) was recorded with potassium-sensitive electrodes in the sensorimotor cortex of cats. Resting activity was 2.8--3.4 mEquiv/l. Electric stimulation of the cortical surface and the nucleus ventroposterolateralis of the thalamus brought about an increase in aK followed by an undershoot and return to normal value. The lowest observed value of aK was 2.1 mEquiv./l. Size and duration (range 0.5--4 min) of the undershoots of aK increased with increasing peak amplitudes of the preceding rise in aK. Following the rise in aK, a period of reduced neuronal activity was observed which usually shorter lasting than the decrease in extracellular aK. An undershoot of aK and a concomitant reduction of neuronal discharge frequency can also occur in immediate response to antidromic stimulation of the pyramidal tract. To compare the K+ redistribution at normal and reduced levels of aK electrophoretic K+ signals were produced with constant current pulses from a proximate KCl-filled capillary. Both amplitudes and half times of decay of these K+ signals were found to decrease during the phase of poststimulatory undershoot in aK (19 and 23% respectively). It is suggested that an activated reuptake of potassium contributes to the decrease in extracellular aK in addition to inhibitory processes.

Animals↗

[Ultrastructural changes in the cerebral cortex of the cat 30 to 60 minutes after anoxia].

The ultrastructural changes in the cat sensorimotor cortex during 30- to 60-minute recovery after a 2.5- to 6-minute anoxia have been studied. The most prominent changes were hypertrophy of Golgi apparatus, reorganization of the neuronal endoplasmic reticulum (including the formation of lamellar bodies), increase of the number of lysosomes within nerve cell bodies, formation of deep invaginations of the neuronal cytoplasm into the nucleus, intensification of endocytosis and phagocytosis in the dendrites, appearance of the ultrastructural heterogeneity of the synapses (from normal synapses to depleted ones), normalization of ultrastructure of the part of mitochondrial pool. Glycogen granules were revealed in glial cell processes. The ultrastructural changes after a 6-minute anoxia followed by a 30- to 60-minute recovery were more expressed than after a 2.5-minute one.

Animals↗

[Distribution of efferent neurons of different types in the motor cortex of the cat].

Distribution of efferent neurones of different categories was studied in the cat sensorimotor cortex: pyramidal and extrapyramidal systems and cortico-thalamic cells, whose axons end in the ventroposterolateral nucleus and medial geniculate body. In the major part of cortical microareas (88%) several output cells were found which could belong equally to one or several different categories. In some vertical cortical tracks no output neurones of the investigated categories were discovered. In tracks with efferent neurones, cortical areas with a definite set of output cells usually represented cylinders of 500-700 mcm in height. Separate microareas differed from each other by sets of fast or slow cells.

Animals↗

[Autocorrelation analysis of background spiking of cortical neurons during learning].

In defensive conditioning of rabbits to light the pattern of the background spike activity (BSA) in the visual cortex did not change in average as compared to the control. In the sensorimotor cortex the spike activity pattern was changed: the afterdischarge inhibition increased. Cells with a regular component in BSA divided into two groups according to the duration of bursts and of inhibitory pauses in the BSA. In the course of conditionings, the number of neurones with non-random components in BSA in the sensorimotor area did not change, while it decreased in the visual area due to a reduction in number of elements with short groups of discharges.

Action Potentials↗

Morphological evidence that reline SMR and human mu are analogous rhythms.

In cats implanted with epidural screw electrodes over sensorimotor cortex, various recording montages were used to observe the waveform of the sensorimotor rhythm (SMR). It was found that in bipolar recordings spanning the crus, SMR exhibited a wicket-shaped waveform comparable in shape and polarity to the human mu rhythm. Based on previously reported topographic and functional similarities of feline SMR and human mu, and on the present data demonstrating morphological similarities, it appears that feline SMR is the first proven feline model of a spontaneous human ieeg rhythm.

Animals↗

[Post-tetanic strengthening of evoked electrical responses of the sensomotor cortex].

A study has been made of the posttetanic potentiation of evoked potentials (PTP EP) in the sensorimotor cortex, appearing in response to VPL stimulation. A distinct PTP EP of the cortical surface has been found as well as considerable differences in its intensity recorded at different portions of deep cortical layers (700 to 1600 mu). Suggestions were made regarding the origin of the phenomena observed.

Animals↗

[Effect of intracellular injections of chloride ion on the inhibitory postsynaptic potential and post-burst hyperpolarization of sensomotor cortex neurons in the cat].

Inversion of the early component of IPSPs in pyramidal neurons of the sensorimotor cortex by intracellular injection of chloride ions was demonstrated in cats immobilized by myorelaxants in acute experiments under moderate composed anesthesia (40 mg/kg nembutal and 20 mg/kg chloralose intraperitoneally). The late component of IPSPs as well as the post-burst hyperpolarization in pyramidal neurons were not inverted. It is concluded that during the early component of IPSPs of both pyramidal and nonpyramidal neurons the membrane permeability is increased for chloride ions, while both the late component of IPSPs and the post-burst hyperpolarization in pyramidal neurons are less dependent on the chloride permeability.

Action Potentials↗

Fate of cerebrospinal fluid-borne amyloid beta-peptide: rapid clearance into blood and appreciable accumulation by cerebral arteries.

In Alzheimer's disease, the neuritic or senile amyloid plaques in hippocampus and association cortex, the diffuse plaques in brain areas such as the cerebellum and sensorimotor cortex, and the amyloid deposits in the walls of pial and parenchymal blood vessels are mainly composed of amyloid beta-peptides. In the present study, either soluble 40-residue amyloid beta-peptide radiolabeled with 125I (I-sAbeta) or [14C]polyethylene glycol ([14C]PEG, a reference material) was briefly infused into one lateral ventricle of normal rats. By 3.5 min, 30% of the I-sAbeta was cleared from ventricular CSF into blood; another 30% was removed over the next 6.5 min. No [14C]PEG was lost from the CSF-brain system during the first 5 min, and only 20% was cleared by 10 min. Much of the I-sAbeta that reached the subarachnoid space was retained by pial arteries and arterioles. Virtually no I-sAbeta was found in brain. The clearance of amyloid beta-peptides from the CSF-brain system, reported herein for normal rats, may be reduced in Alzheimer's disease, thus contributing to amyloid deposition in cerebral tissue and blood vessels.

Amyloid beta-Peptides↗

The effect of epidural compression on cerebral cortex: a rat model.

We developed a rat model of epidural plastic bead implantation to study the effect of physical compression on the cerebral cortex. Epidural implantation of a bead of appropriate size compressed the underlying sensorimotor cortex without apparent ischemia, since the capillary density of the cortex was increased. Although the thickness of all layers of the compressed cortex was significantly decreased, no apparent changes in the number of NADPH-diaphorase reactive neurons, reactive astrocytes, or microglial cells were observed, nor were apoptotic neurons observed. In fact, the densities of the neurons in most cortical layers apparently increased. To determine how epidural compression affects neuronal morphology, the dendritic arbors of layer III and V pyramidal neurons were evaluated using a fixed tissue intracellular dye injection technique. Neurons in both layers remained pyramidal in shape and their somatic sizes remained unaltered for at least a month after compression. On the other hand, their total dendritic length was significantly reduced beginning at 3 days post implantation. These analyses showed that apical dendrites were affected sooner than basal ones. The reduction of dendritic length was associated with a drop in the number of dendritic branches rather than dendritic trunks, suggesting the trimming of the peripheral part of the dendritic arbor. Detailed analysis showed that dendritic spines on all dendrites were reduced as early as 3 days following implantation. These results suggest that cortical neurons remodel their structures substantially within 3 days after being subjected to epidural compression.

Animals↗

A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies.

The role of the basal ganglia and cerebellum in the control of movements is unclear. We summarize results from three groups of PET studies of regional CBF. The results show a double dissociation between (i) selection of movements, which induces differential effects in the basal ganglia but not the cerebellum, and (ii) sensory information processing, which involves the cerebellum but not the basal ganglia. The first set of studies concerned motor learning of a sequence of finger movements; there was a shift of activation in the anterior-posterior direction of the basal ganglia which paralleled changes in the motor areas of the frontal cortex. During new learning, the dorsolateral prefrontal cortex and striatum (caudate nucleus and anterior putamen) were activated. When subjects had to select movements, the premotor cortex and mid-putamen were activated. With automatic (overlearned) movements, the sensorimotor cortex and posterior putamen were activated. When subjects paid attention to overlearned actions, activation shifted back to the dorsolateral prefrontal cortex and striatum. The cerebellum was not activated when subjects made new decisions, attended to their actions or selected movements. These results demonstrate components of basal ganglia-(thalamo)-cortical loops in humans. According to earlier studies in animals we propose that the basal ganglia may be concerned with selecting movements or the selection of appropriate muscles to perform a movement selected by cortical areas (e.g. premotor cortex). Secondly, a visuomotor co-ordination task was examined. In the absence of visual control over arm movements, subjects were required to use a computer mouse to either generate new lines or to re-trace lines on a computer screen. The neocerebellum (hemispheres of the posterior lobe, cerebellar nuclei and cerebellar vermis), not the basal ganglia, was more engaged when lines were re-traced (compared with new line generation). Animal experiments have shown that error detection (deviation from given lines) and correction occurs during line re-tracing but not line generation. Our data suggest that the neocerebellum (not the basal ganglia) is involved in monitoring and optimizing movements using sensory (proprioceptive) feedback. Thirdly, the relative contribution of sensory information processing to the signal during active/passive execution of a motor task (flexion and extension of the elbow) was examined; it was found that 80-90% of the neocerebellar signal could be attributed to sensory information processing. The basal ganglia were not involved in sensory information processing. They may be concerned with movement/ muscle selection (efferent motor component); the neocerebellum may be concerned with monitoring the outcome (afferent sensory component) and optimizing movements using sensory (feedback) information.

Basal Ganglia↗

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex.

OBJECT: The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed. METHODS: The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image and the image data set was implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyri were identified by neuronavigation and, in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the procedure. CONCLUSIONS: The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to lessen morbidity around eloquent brain areas.

Adolescent↗

[Dependence of different spike sequences on the mean neuronal firing rate in the neocortex in vivo and in vitro].

Neuronal spikes were recorded extracellularly in rabbit visual cortex in vivo (88 cells) and in surviving slices of guinea pig sensorimotor cortex in vitro (50 cells). Spike sequences (SS) with monotonically increasing (SS+) and decreasing (SS-) interspike intervals were detected. Relative number of spikes of SS in the recording was closely associated with SS generation. The relative number of spikes was plotted against the average firing rate, this function had a biphasic character with the critical point around 7 Hz. The rate of change in interspike duration (the slope) was virtually independent of the firing rate, but was significantly different in vivo and in vitro conditions for both SS+ (325 and 180 ms/s, respectively) and SS- (270 and 160 ms/s, respectively). By and large, in vivo and in vitro the spike sequence parameters depended in the average firing rate in the same manner. The role of the spike sequences in rhythmic and information processes in neocortex is discussed.

Action Potentials↗

[Electrophysiologic study of the ascending connections of the hippocampus with various neocortical zones in the rabbit].

In acute experiments on rabbits studies have been made on functional connections of hippocampal fields CA1 and CA3 with various zones of the neocortex. It was shown that these hippocampal structures are most closely connected with the limbic ancient associative cortex, as well as with the parietal and temporal regions. In the sensorimotor cortex, the EPs were rather irregular. Fields CA1 and CA3 exhibit different projections to the mentioned regions of the neocortex.

Afferent Pathways↗