Motor Cortex Ablation Research Articles

Cell Proliferation in the Piriform Cortex of Rats with Motor Cortex Ablation Treated with Growth Hormone and Rehabilitation.

Traumatic brain injury represents one of the main health problems in developed countries. Growth hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for four days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted a greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.

In vivo bioluminescence imaging for prolonged survival of transplanted human neural stem cells using 3D biocompatible scaffold in corticectomized rat model.

Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA) scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc) were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups.Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls.GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion.Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area).

Motor cortex stroke impairs individual digit movement in skilled reaching by the rat

Over 30 years ago, Castro [(1972) Brain Res., 37, 173-185] proposed that motor cortex (MtCx) ablation produced deficits in digital usage that contributed to the rat's impairments in a reach-to-eat task, but the impairment was not directly documented. The present study examined digit use in control rats and rats with MtCx lesions using high-speed (1000 f/s) video recording. Temporal and spatial characteristics of individual digits were evaluated by digitizing the tip of the digits and digital joints using the motion measurement system Peak Motus. Control rats displayed differential digital use during grasping actions and MtCx damage reduced individual digit movement, both as the paw was pre-shaped for grasping and in the grasping action itself. The findings show that although grasping is retained following MtCx damage, MtCx is essential for dexterous movement. The results are discussed in relation to the idea that rodent MtCx is not only necessary for rotatory movements of the limb, but also for digital control and in relation to the similarities of rodent digit use to that described for primates.

What Generates Whisking? Focus on: “The Whisking Rhythm Generator: A Novel Mammalian Network for the Generation of Movement”

A central goal of neuroscience is to explain how neural networks generate organized and repetitive motor patterns, such as active whisking used by rodents to navigate the environment. Whisking consists of fast rhythmic ellipsoid vibrissae movements through the air and over objects at between 4 and

Motor Function in Young and Aged Hemiplegic Rats: Effects of a Ginkgo Biloba Extract

We have previously shown beneficial effects of a Ginkgo biloba extract (EGb761-IPSEN) in accelerating functional recovery from hemiplegia induced by unilateral motor cortex ablation. Here, we report the behavioral and histological effects of various dose regimes of EGb761. In young rats (3 months), 10 mg/kg/day for 7 days produced an improvement in motor performance, relative to untreated controls, on the last day of treatment. Applying a priming (P)-maintenance (M) dose regime (P-7 = 7 days, M-21 = 21 days), a P-7 of 50 (all doses expressed in mg/kg/day) and a M-21 of 10 promoted recovery from the second day after surgery. However, in aged rats (26–28 months old) this treatment ameliorated motor performance only after the 10th day of treatment. A P-7 of 100 or 200 and a M-21 of 50 or 100 produced an acceleration of behavioral recovery in aged animals. Improvement was evident by the fifth day of treatment and was maintained after the treatment regimen. These two groups also demonstrated reduced glial fibrillary acid protein (GFAP) immunostaining and ex vacuo hydrocephalus. Thus, the confirmed efficacy of EGb in hemiplegic rats can be enhanced by an appropriate posology.

Functional recovery of forelimb response capacity after forelimb primary motor cortex damage in the rat is due to the reorganization of adjacent areas of cortex

Functional recovery after brain damage has been described frequently and different mechanisms have been proposed to account for the observed recovery. One possible mechanism involves the capacity of one part of the brain to take over the function of another. A possible area for this to take place is in the cerebral cortex, where a variety of reorganizational processes have been described after different manipulations. We show in the present study that the forelimb force and response capacity of the rat, which becomes highly impaired after the bilateral ablation of the forelimb primary motor cortex, is recovered when the animals receive an electrical stimulation in the ventral tegmental nucleus contingent to each forelimb response in the task. Microstimulation mapping of the cortical areas adjacent to the forelimb primary motor cortex revealed the appearance of an area located caudolaterally to the forelimb primary motor cortex, where forelimb movements could be evoked in recovered animals but to a lesser extent in non-recovered animals. A positive and significant correlation was observed between the size of the reorganized forelimb area and the behavioral performance of the animals. Ablation of the forelimb reorganized area in recovered animals reinstated the forelimb behavioral impairment, while the same lesion in normal animals had no effect on the behavioral performance. The results indicate that recovery after bilateral forelimb primary motor cortex ablation may be due to the organization of specific adjacent areas in the cortex.

Activity of area 5 neurons in monkeys during arm movements: effects of dentate nucleus lesion and motor cortex ablation

Area 5 movement-related neurons were recorded in two trained monkeys respectively before and after (i) bilateral lesion of the dentate nucleus (DN), (ii) ablation of the motor cortex (area 4). DN lesion does not modify the proportion of early (command) and late (somaesthetic) neuronal changes. It does, however, increase both cellular and behavioural reaction times. The ablation of area 4 induces a clear-cut increase in the number of early neuronal changes during the period of recovery from arm palsy. These results show that: (i) the neocerebellum enhances the excitability of area 5 movement-related neurons; (ii) area 5 may compensate for the deficiency in area 4 by unmasking silent neurons and thereby subserves rehabilitation mechanisms.

Acceleration of functional recovery from motor cortex ablation by two Ginkgo biloba extracts in rats

We studied the effects of two extracts of Ginkgo biloba, with and without terpenes, on motor recovery from cortical hemiplegia. Both extracts of the reference product (EGb761-IPSEN) produced a dose-dependent acceleration of behavioral recovery and diminished ventricular dilation in lesion rats. These results indicate that the active substance(s) participating in the beneficial effect of EGb761 is (are) contained in the non-terpenic fraction of the extract.

Differences in the recovery rate of a learned forelimb movement after ablation of the motor cortex in right and left hemisphere in white rats

After ablation of the motor cortex contralateral to the preferred limb, rats were forced to use this limb in grasping food out of a horizontal tube by restraining the non-preferred foreleg with a bracelet. In a right-handed rat the motor behaviour is less impaired and the recovery is better after a left hemisphere lesion in comparison with a left-handed rat after a right hemisphere lesion. This difference is primarily the time needed to use the limb in reaching for seed (testperiod 3) and the total time needed for 10 successive seizings of seed (testperiod 5). Surprisingly, the differences in the course of recovery do not correlate with the degree of preoperative limb preference: the initially ambidextrous rate also show the same differences in results of the motor cortex ablation in left and right hemisphere. However, in the group of initially consistent ambidextrous rats, after 10 weeks of tests with a restrained forelimb, the testing under unrestrained free conditions shows a gradual decrease in the induced limb preference and a shift to the use of the foreleg contralateral to the intact hemisphere, while in contrast the initially consistent left- or right-handed rats preserve the limb preference under the unrestrained testing conditions. Therefore the degree of initial preference still influences the choice of limb after motor cortex ablation and intensive training to use the ‘damaged’ limb.

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)

Cortex, striatum and cerebellum: control of serial order in a grooming sequence.

Rats emit grooming actions in sequences that follow characteristic patterns of serial order. One of these patterns, a syntactic chain, has a particularly stereotyped order that recurs spontaneously during grooming thousands of times more often than could occur by chance. Previous studies have shown that performance of this sequence is impaired by excitotoxin lesions of the corpus striatum. In this study we examined whether the striatum is unique in its importance to this behavioral sequence or whether control of the sequence instead depends equally upon the cortex and cerebellum. In two experiments, a fine-grained behavioral analysis compared the effects of striatal ablation to the effects of motor cortex ablation, ablation of the entire neocortex, or ablation of the cerebellum. Cortical and cerebellar aspiration produced mere temporary deficits in grooming sequences, which appeared to reflect a general factor that was nonsequential in nature. Only striatal damage produced a permanent sequential deficit in the coordination of this syntactic grooming chain. We conclude that the striatum has a unique role in the control of behavioral serial order. This striatal role may be related to a number of sequential disorders observed in human diseases involving the striatum.

Low threshold unilateral and bilateral facial movements evoked by motor cortex stimulation in cats

Organizational features of the ipsilateral representation in the cat face motor cortex were investigated by using the technique of intracortical microstimulation (< 30 μA). In 4 intact animals, 61 efferent zones controlling facial muscles were identified. They were devoted to contralateral muscles (contralateral efferent zones; n = 35), ipsilateral muscles (ipsilateral efferent zones; n = 8) or symmetrical muscles of both sides (bilateral efferent zones; n = 18). Contralateral efferent zones were found within both the rostral part of the coronal gyrus and the lateral bank of the presylvian sulcus, whereas ipsilateral and bilateral efferent zones were exclusively localized to the rostromedical region of the face motor cortex. Movement thresholds proved to be lowest at the contralateral efferent zones and highest at the ipsilateral efferent zones, with intermediate values at the bilateral efferent zones. Latencies of suprathreshold EMG responses evoked from contralateral and ipsilateral efferent zones were the shortest and the longest, respectively; intermediate values were found upon stimulation of sites from bilateral efferent zones. The efferent zones identified in 3 lesioned animals (two cats with contralateral motor cortex ablation and one cat with transection of the rostral two thirds of the corpus callosum) were contralateral ( n = 14), bilateral ( n = 13), and ipsilateral ( n = 9). Mean thresholds of effective sites from bilateral and ipsilateral efferent zones in lesioned preparations were not significantly higher than those in intact animals. This would thus suggest that extracallosal pathways may account for ipsilateral responses.

Motor neuron organization and corticospinal fibers in the cervical intumescence of the raccoon (Procyon lotor) spinal cord.

SummaryExperiments were performed on 19 raccoons to determine the organization of the spinal alpha motoneurons innervating the muscles of the thoracic limb. Chromatolysis of motoneurons was provoked by resecting major nerves or removing individual muscles or muscle groups. Proximal intrinsic limb muscle motoneurons were located cranially in the cervical spinal intumescence and distal muscle motoneurons more caudally. Flexor motoneurons were generally dorsal and more laterally located within the lateral motoneuronal cell group than were the cell bodies innervating their extensor antagonists. The distribution of motor cortex projections to motoneurons was studied in five raccoons by selective silver impregnation of degenerating fibers after unilateral motor cortex ablation. Degenerating cortical projections within the motoneuronal cell group (Rexed's lamina IX) were seen only in the more dorsal and the lateral portions in the seventh and eighth cervical and the first thoracic spinal cord segments. Motor cortex preterminal and terminal fibers were in close apposition to the proximal dendrites and the somata of alpha motoneurons innervating primarily the more distal limb musculature and particularly the intrinsic muscles of the manus.

Motor responses mediated by orthodromic and antidromic activation of the rostral portion of the cat corpus callosum.

The effects of microstimulation of the rostral portion of the corpus callosum (CC) were examined in seven chronic cats submitted to either unilateral motor cortex ablation (5 preparations) or transection of the rostral two thirds of the CC (2 preparations) in order to identify the routes (ortho- or antidromic) followed by callosal impulses to provoke the motor effects. As in intact animals, motor responses in lesioned preparations consisted of very localized contractions of shoulder, whisker, or eyelid muscles, according to the stimulated sites. Unlike intact animals in which motor responses upon CC microstimulation were bilateral and symmetrical (Spidalieri and Guandalini 1983), in lesioned preparations they appeared contralaterally to the emitting hemisphere, i.e., they were contralateral to the stimulated callosal stump (split-brain preparations) and ipsilateral to the side of the cortical lesion (preparations with unilateral motor cortex ablation), regardless of the current intensity applied (up to a maximum of 50 microA). The unilateral motor responses occurred by the first day after lesion and persisted for the duration of the experiments which lasted to a month or more. Since orthograde degeneration of callosal fibres deprived of their somata has been shown by previous anatomical studies to be complete within 11 days after lesion, these results indicate that selective antidromic activation of callosal fibres is capable of eliciting motor responses. Thresholds for the motor effects in lesioned preparations proved to be from 1.3 to 3.9 (mean, = 2.4 +/- 0.7 SD) times higher than those found before motor cortex ablation. By 18 days after lesion a decrease of threshold currents for the motor responses was observed ranging from 6 to 37% (mean, = 24.2 +/- 13.6 SD), depending on the stimulated sites, relative to values previously found. The shortest train duration and the lowest frequency for minimum threshold were longer (40 vs. 30 ms) and higher (400 vs. 300 Hz), respectively in lesioned preparations than in intact controls. Moreover, a decrease in train duration or frequency provoked larger threshold increases in lesioned preparations than those observed in intact animals. As a whole, these results suggest that in intact animals the motor effects are also mediated by orthodromic callosal volleys.

Effects of frontal motor cortex ablation on the ultrastructure of cat substantia nigra.

3,4 and 5 days after the removal by suction of the left motor and premotor cortex in cats, the presence of ultrastructural changes in the substantia nigra was investigated. Whereas after 3 days dark bouton degeneration was rare, after 4- and 5-day survival it was regularly found for a distinct type of synapse containing in its bouton densely packed small round vesicles and possessing an asymmetric synaptic junction with a dendrite. Often these darkly degenerated boutons contained dense bodies which were also observed in the same type of synapse not yet exhibiting a dark axoplasm. Various inclusions, especially glycogen depots, were present in these boutons suggesting that they were in the process of degeneration. The glial reaction was comparatively severe. In addition, darkly shrunken dendrites contacted both, by intact and by altered boutons were frequently encountered as well as single degenerated neuronal perikarya. The nature of this effect, i.e. whether transneuronal or retrograde, could not be clarified. All these alterations were found bilaterally after the unilateral cortex ablation, and were confined to the substantia nigra pars compacta along its whole anterior-posterior extent. In the pars reticulata, solely traversing myelinated axons in the process of degeneration were observed. Thus, the results are in agreement with the older studies and with evidence from primates demonstrating that the substantia nigra receives a bilateral projection from the motor and premotor cortex.

Effect of motor and premotor cortex ablation on concentrations of amino acids, monoamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter.

At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

Rehabilitation following brain damage: some neurophysiological mechanisms. Physiological correlates of clinically observed changes in posture and tone following lesions of the central nervous system.

Extensive investigation of the role of the fusimotor system in the production of hypotonic and hypertonic disorders of posture and tone has been undertaken in humans and experimental animals. The data from human studies have usually been from indirect assessment of the fusimotor system, and results are often contradictory. Results are now available from animal studies utilizing direct recording of muscle spindle afferent discharge in a number of models of human disorder. Conditions resulting in hypotonia, e.g. cerebellar ablations, medullary pyramidotomy, VL nucleus, thalamotomy, acute spinal cord transection, and acute motor cortex ablation uniformly result in a depression of muscle spindle primary afferent discharge. Conditions resulting in hypertonia, e.g. chronic spinal cord transection and chronic motor cortex ablation, fail to show heightened muscle spindle afferent discharge, however. Rather the spindle afferent discharge returns to control levels in the models. Recovery from the hypotonic to the hypertonic state is, however, associated with significant recovery of spindle afferent function.

A comparison of the role of the motor cortex in recovery from cerebellar damage in young and adult rats

These experiments compare the motor development of rats with hemicerebellectomies performed at 10, 15, or 21 days of age. In addition, the effects of secondary motor cortex lesions are contrasted in these young-lesioned groups and in adults with similar cerebellar damage after the same post-operative interval. Of the young-lesioned groups, the 10-day operates showed the longest persistence of cerebellar symptoms, while the 21-day animals recovered normal motor patterns most quickly. The adult operates were also comparatively slow to eliminate motor behaviors characteristic of cerebellar damage. Following secondary bilateral motor cortex ablation, the greatest reinstatement of cerebellar symptoms occurred in the 10-day group, while the 21-day animals and adults were the least affected. These results are discussed in terms of possible mechanisms of functional recovery in the young and adult groups.

Fiber-analytical studies of the pyramidal tracts following unilateral motor cortex ablation in monkeys.

Fiber-analytical studies of the pyramidal tracts following unilateral motor cortex ablation in monkeys.