Chronic effects of total or partial digit denervation on raccoon somatosensory cortex.

Electrophysiological recordings were made in the primary somatosensory cortex of anesthetized raccoons 14 to 169 days following digit amputation or 60 to 129 days after transection of the two nerves innervating the ventral surface of the fourth digit. The incidence of inhibitory responses decreased from 50% of the penetrations immediately after amputation to 35% over the first 3 weeks and to almost zero after 2 months. The number of sites with low-threshold excitatory responses increased from 4% to 14% to 50% during these same intervals. Initially, the excitatory fields were small and located over the nerve stumps, and were therefore probably due to direct stimulation of the damaged nerves. At 2 months after amputation, the excitatory receptive fields were large and diffuse. Although the size of receptive fields decreased during the later period (when the thresholds were also decreasing), there was no recovery of any precise somatotopic organization in the deafferented cortex. The reorganization process in the raccoon thus consists of at least two stages: The early stage is dominated by inhibitory connections, whereas the second involves a recovery and restructuring of excitatory inputs. From 2 to 4 months after partial digit denervation, there were only minor changes in response properties or somatotopic organization in the deafferented cortex as compared to immediately after nerve transection. Thus, few of the characteristics of reorganization induced by digit amputation were elicited by this treatment, which leaves some of the digit innervation intact. There was, however, an unexpected increase in the portion of the ventral digit that was able to activate the cortex, suggesting complexities in the peripheral innervation of the digit that need to be resolved.     

Chronological observations of primary somatosensory cortical maps in kittens following low thoracic (T12) spinal cord transection at 2 weeks of age.

The present study investigated the reorganization of the somatosensory cortex in kittens following T12 spinal cord transection at 2 weeks of age. Multiunit electrophysiological methods were used to map the somatosensory cortex of kittens at 3, 6, and 9 weeks after the transection. The entire reorganized cortical region was driven by substitute cutaneous inputs, primarily from the trunk, at 3 weeks after spinal cord transection. Although the level of cortical responsiveness remained the same throughout the 9 weeks studied, internal trunk representation changed, and there was an increase in shoulder girdle representation and emergence of forelimb representation. Poor somatotopic and topographic order was observed in the reorganized cortex, regardless of time posttransection. Finally, trunk receptive fields displayed a wide variety of shapes, sizes, and orientations not seen in the normal cortex.     

Chronological Observations of Primary Somatosensory Cortical Maps in Kittens following Low Thoracic (T12) Spinal Cord Transection at 2 Weeks of Age

The present study investigated the reorganization of the somatosensory cortex in kittens following T₁₂ spinal cord transection at 2 weeks of age. Multiunit electrophysiological methods were used to map the somatosensory cortex of kittens at 3, 6, and 9 weeks after the transection. The entire reorganized cortical region was driven by substitute cutaneous inputs, primarily from the trunk, at 3 weeks after spinal cord transection. Although the level of cortical responsiveness remained the same throughout the 9 weeks studied, internal trunk representation changed, and there was an increase in shoulder girdle representation and emergence of forelimb representation. Poor somatotopic and topographic order was observed in the reorganized cortex, regardless of time posttransection. Finally, trunk receptive fields displayed a wide variety of shapes, sizes, and orientations not seen in the normal cortex.     

Extrapyramidal descending influences on neurons of the spinal cord in a superreflexia state

The spinal superreflexia state was modeled in experiments on rats using preliminary transection of the spinal cord and injection (in the course of the acute experiment) of 4-aminopyridine. An extremely high (reaching 15–20 mV) amplitude of monosynaptic reflex discharges (MRs) evoked by stimulation of the dorsal root and recorded from the ventral root (VR) L ₄ and the presence of an additional component in the above discharges were phenomena indicative of the development of the above state. Under such conditions, the amplitudes of the discharges evoked in the VR by electrical stimulation of the round window of the labyrinth (vestibular stimulation) and of the discharges elicited by stimulation of the motor cortex under conditions of bilateral transection of the pyramids increased several times. Thresholds of the VR responses to vestibular and cortical stimulations demonstrated an about threefold drop; latencies of the mass responses and responses of single spinal moto-and interneurons decreased about twofold, on average. The pattern of vestibular conditioning effects on the VR MRs changed: in intact animals vestibular stimulation induced inhibition of the VR MRs, while in animals with superreflexia such stimulation led to facilitation of the MRs. Cortical stimulation under conditions of pyramidotomy in both intact animals and animals with superreflexia resulted in facilitation of the VR MRs of a nearly the same intensity. The levels of convergence of the segmental and supraspinal effects on interneurons and motoneurons of the rat spinal cord dramatically increased under superreflexia conditions. The possible mechanisms of augmentation of the descending influences on spinal neuronal systems under the above conditions are discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 2, pp. 140–149, March–April, 2006.     

Nonoverlapping Thalamocortical Connections to Normal and Deprived Primary Somatosensory Cortex for Similar Forelimb Receptive Fields in Chronic Spinal Cats

The fluorescent dye retrograde tracing technique, using fast blue in combination with fluorogold, was used to examine thalamocortical projections from the ventrobasal complex to primary somatosensory cortex in chronic spinal cats that sustained T12 cord transection at 2 weeks of age. Following cord transection at this age, it has been shown that forelimb afferents can excite the deprived hindlimb projection zone, in addition to the region of somatosensory cortex that they normally occupy (McKinley et al, 1987). These two regions of cortex are separated by over 10 mm, thus facilitating the determination of whether the forelimb representation in “hindlimb cortex” is derived from the sector of the ventrobasal complex of the thalamus representing the forelimb, hindlimb, or both. Injections of the two dyes into separate regions of the cortex that were excited by the same peripheral forelimb receptive fields produced single labeling of two nonoverlapping clusters of thalamic neurons. This finding suggests that the projections for these two areas are independent and distinct, and indicates that altered thalamocortical projections do not contribute the critical component underlying reorganizational changes observed at the cortical level after spinal cord transection. It is hypothesized that the degree of reorganization required to achieve the magnitude of change observed in the cortex must occur below the level of the thalamocortical relay.     

Areal Distributions of Cortical Neurons Projecting to Different Levels of the Caudal Brain Stem and Spinal Cord in Rats

Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Ag_m), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb.

The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI. Injections in lateral SI representing the face produced dense terminal label in the contralateral trigeminal complex. Injections in cortex devoted to the forelimb and forepaw labeled the contralateral cuneate nucleus and parts of the dorsal horn of the spinal cord. The cortical injections also demonstrated interconnections of parts of SI with some of the other regions of cortex with projections to the spinal cord, and provided further evidence for the existence of PV in rats.     

Areal distributions of cortical neurons projecting to different levels of the caudal brain stem and spinal cord in rats

Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Agm), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb. The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI.(ABSTRACT TRUNCATED AT 400 WORDS)     

Restoration of contralateral representation in the mouse somatosensory cortex after crossing nerve transfer

Avulsion of spinal nerve roots in the brachial plexus (BP) can be repaired by crossing nerve transfer via a nerve graft to connect injured nerve ends to the BP contralateral to the lesioned side. Sensory recovery in these patients suggests that the contralateral primary somatosensory cortex (S1) is activated by afferent inputs that bypassed to the contralateral BP. To confirm this hypothesis, the present study visualized cortical activity after crossing nerve transfer in mice through the use of transcranial flavoprotein fluorescence imaging. In naïve mice, vibratory stimuli applied to the forepaw elicited localized fluorescence responses in the S1 contralateral to the stimulated side, with almost no activity in the ipsilateral S1. Four weeks after crossing nerve transfer, forepaw stimulation in the injured and repaired side resulted in cortical responses only in the S1 ipsilateral to the stimulated side. At eight weeks after crossing nerve transfer, forepaw stimulation resulted in S1 cortical responses of both hemispheres. These cortical responses were abolished by cutting the nerve graft used for repair. Exposure of the ipsilateral S1 to blue laser light suppressed cortical responses in the ipsilateral S1, as well as in the contralateral S1, suggesting that ipsilateral responses propagated to the contralateral S1 via cortico-cortical pathways. Direct high-frequency stimulation of the ipsilateral S1 in combination with forepaw stimulation acutely induced S1 bilateral cortical representation of the forepaw area in naïve mice. Cortical responses in the contralateral S1 after crossing nerve transfer were reduced in cortex-restricted heterotypic GluN1 (NMDAR1) knockout mice. Functional bilateral cortical representation was not clearly observed in genetically manipulated mice with impaired cortico-cortical pathways between S1 of both hemispheres. Taken together, these findings strongly suggest that activity-dependent potentiation of cortico-cortical pathways has a critical role for sensory recovery in patients after crossing nerve transfer.     

Behavioral plasticity and central regeneration of locomotor reflexes in the freshwater oligochaete, Lumbriculus variegatus. I: Transection studies

Abstract. Access to the ventral nerve cord in living specimens of Lumbriculus variegatus , an aquatic oligochaete, is normally impossible because surgical invasion induces segmental autotomy (self-fragmentation). We show here that nicotine is a powerful paralytic agent that reversibly immobilizes worms, blocks segmental autotomy, and allows experimental access to the nerve cord. Using nicotine-treated worms, we transected the ventral nerve cord and used non-invasive electrophysiological recordings and behavioral analyses to characterize the functional recovery of giant nerve fibers and other reflex pathways. Initially, after transection, medial giant fiber (MGF) and lateral giant fiber (LGF) spikes conducted up to, but not across, the transection site. Reestablishment of MGF and LGF through-conduction across the transection site occurred as early as 10 h (usually by 20 h) after transection. Analyses of non-giant-mediated behavioral responses (i.e., helical swimming and body reversal) were also made following nerve cord transection. Immediately after transection, functional reorganization of touch-evoked locomotor reflexes occurred, so that the two portions of the worm anterior and posterior to the transection site were independently capable of helical swimming and body reversal responses. Similar reorganization of responses occurred in amputated body fragments. Reversion back to the original whole-body pattern of swimming and reversal occurred as early as 8 h after transection. Thus, functional restoration of the non-giant central pathways appeared slightly faster than giant fiber pathways. The results demonstrate the remarkable plasticity of locomotor reflex behaviors immediately after nerve cord transection or segment amputation. They also demonstrate the exceptional speed and specificity of regeneration of the central pathways that mediate locomotor reflexes.     

Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses.

The adult central nervous system (CNS) of higher vertebrates displays a limited ability for self repair after traumatic injuries, leading to lasting functional deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3,4]. In the sensory system, studies have shown that cortical and subcortical mechanisms contribute to map rearrangements [5,6], but for the motor system the situation is less clear. Here we show that large-scale structural changes in the spared rostral part of the spinal cord occur simultaneously with shifts of a hind-limb motor cortex representation after traumatic spinal-cord injury. By intracortical microstimulation, we defined a cortical area that consistently and exclusively yielded hind-limb muscle responses in normal adult rats. Four weeks after a bilateral transsection of the corticospinal tract (CST) in the lower thoracic spinal cord, we again stimulated this cortical field and found forelimb, whisker, and trunk responses, thus demonstrating reorganization of the cortical motor representation. Anterograde tracing of corticospinal fibers originating from this former hind-limb area revealed that sprouting greatly increased the normally small number of collaterals that lead into the cervical spinal cord rostral to the lesion. We conclude that the corticospinal motor system has greater potential to adapt structurally to lesions than was previously believed and hypothesize that this spontaneous growth response is the basis for the observed motor representation rearrangements and contributes to functional recovery after incomplete lesions.     

Effect of Oxotremorine on Ornithine Decarboxylase Activity of the Adrenal Gland in Rat

Abstract: In this work we have studied the mechanism for the increase of adrenal ODC (ornithine decarboxylase, EC 4.1.1.17) activity provoked by oxotremorine, a muscarinic agonist. 1. Oxotremorine increased medullary ODC activity maximally at 2 h. Cortical enzyme responded much more slowly. 2. Blockade of peripheral muscarinic receptors with methylatropine partially reduced the response to oxotremorine in the medulla, but not cortex. 3. Hy-pophysectomy abolished the cortical, but not the medullary, responses to oxotremorine. Methylatropine reduced the effect of oxotremorine on medullary ODC in hypophysectomized rats. 4. In unilaterally splanchnicotomized rats oxotremorine caused an increase of ODC activity of the denervated adrenal gland relative to control value; activities in both medulla and cortex were significantly lower than those observed in the innervated gland. Evidence was obtained for a compensatory increase of ODC activity of the adrenal cortex (but not medulla) on the intact side of unilaterally operated rats. 5. Surgical intervention, in the form of a sham operation for transection of the spinal cord, leads to an increase of ODC activity in both parts of the adrenal gland. Transection of the cord attenuates these increases. 6. The additional increase of medullary ODC activity owing to the administration of oxotremorine to sham-operated rats is partially reduced in the adrenal medulla by muscarinic blockade, and completely in the cortex. This effect of methylatropine in regard to cortical ODC activity was not apparent in the other experiments with intact or unilaterally splanchnicotomized (unoperated side) rats. The results with unilaterally splanchnicotomized rats and those with transected spinal cord suggest that oxotremorine-induced modifications of adrenal ODC activity are centrally mediated, above the level of origin of the splanchnic nerves in the spinal cord (T_8–10). Experiments with hypophysectomized rats show that the response of the adrenal cortex to oxotremorine is entirely mediated by the hypophysis.     

Basal forebrain lesions with or without reserpine injection inhibit cortical reorganization in rat hindpaw primary somatosensory cortex following sciatic nerve section.

To test the hypothesis that cortical reorganization depends on acetylcholine and one or more of the monoamines, the hindpaw cortex was mapped in eight different groups of mature rats: (1) untreated; (2) after sciatic nerve transection; (3) after intraperitoneal injections of reserpine, to reduce the level of cortical monoamines; (4) after ibotenic acid lesion of the nucleus basalis of Meynert (NBM), to destroy cholinergic cells projecting to the cortex; (5) after reserpine treatment and transection; (6) after ibotenic acid lesion and transection; (7) after reserpine treatment and ibotenic acid lesion; and (8) after reserpine treatment, ibotenic acid lesion, and transection. Four days after transection, the cortex had reorganized in the transected group. However, this process of reorganization was prevented in transected animals with NBM lesions. Treatment with reserpine alone did not inhibit the process of reorganization, nor did it enhance the effect of NBM lesion. Nonetheless, the animals treated with reserpine and transected had higher response thresholds in the reorganized cortex than did the animals that were treated but not transected. These data suggest that acetylcholine plays an important role in the early reorganization that follows deafferentation, and that one or more of the monoamines may have other influences on reorganization of the primary somatosensory cortex of adult rats.     

Changes in extracellular levels of dopamine metabolites in somatosensory cortex after peripheral denervation

This study examined the effects of a nerve transection on monoamine release from primary somatosensory cortex. The technique of microdialysis was employed to sample extracellular levels of norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the barrel field of freely moving rats following the surgical transection of the contralateral infraorbital nerve. Microdialysates obtained 3, 4, and 5 days after deafferentation were analyzed using high-performance liquid chromatography with electrochemical detection. We found a significant increase in the release of the dopamine metabolites, DOPAC and HVA from the deafferented cortex. Three days after deafferentation the release of DOPAC was three-fold higher in the deafferented than in the control animals, and remained about 100% higher in the next two days in this group of animals. The release of HVA showed a gradual increase following the deafferentation procedure, since a 92% larger value on day 3 increased to a 338% difference on day 5. On the other hand, the release rate of NE and the levels of the serotonin metabolite 5-HIAA were not significantly affected by the deafferentation procedure. These results are discussed in the context of the possible participation of dopamine in the reorganization of the deafferented somatosensory cortex.     

Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5-C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury.     

Tail-flick latency and self-mutilation following unilateral deafferentation in rats

Unilateral deafferentation induced by transection of the C(4)-C(8) dorsal roots of spinal cord, followed by a complex of abnormal self-mutilating behavior, is interpreted as an animal model of chronic nociception. The objective of our study was to test the differences in tail-flick latency between intact control and unilaterally deafferented animals and to assess the changes in their acute nociceptive sensation. The initial hypothesis was that deafferentation-induced painful sensation might cause stress-induced analgesia that should be manifested as prolonged tail-flick latency. The experiment was carried out on 11 male and 10 female adult Wistar rats. The tail-flick latency was repeatedly measured over a period of 10 consecutive weeks both in the preoperative baseline period and following multiple cervical dorsal rhizotomy. Contrary to our hypothesis, unilateral deafferentation was followed by a significant shortening of the tail-flick latency both in males and females. In deafferented animals, compared to the controls, variations of tail-flick latency were reduced. In individual animals after deafferentation, concurrent dynamic changes were observed in self-mutilating behavior, in a loss and regaining of body weight, and in tail-flick latency. Our data suggest that changes in tail-flick latency may be interpreted in terms of central sensitization and that tail-flick latency might be considered as a useful marker of chronic nociception.     

Imaging the spatio-temporal dynamics of supragranular activity in the rat somatosensory cortex in response to stimulation of the paws

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli.     

LPA receptor expression in the central nervous system in health and following injury

Lysophosphatidic acid (LPA) is released from platelets following injury and also plays a role in neural development but little is known about its effects in the adult central nervous system (CNS). We have examined the expression of LPA receptors 1-3 (LPA_1–3) in intact mouse spinal cord and cortical tissues and following injury. In intact and injured tissues, LPA₁ was expressed by ependymal cells in the central canal of the spinal cord and was upregulated in reactive astrocytes following spinal cord injury. LPA₂ showed low expression in intact CNS tissue, on grey matter astrocytes in spinal cord and in ependymal cells lining the lateral ventricle. Following injury, its expression was upregulated on astrocytes in both cortex and spinal cord. LPA₃ showed low expression in intact CNS tissue, viz. on cortical neurons and motor neurons in the spinal cord, and was upregulated on neurons in both regions after injury. Therefore, LPA_1–3 are differentially expressed in the CNS and their expression is upregulated in response to injury. LPA release following CNS injury may have different consequences for each cell type because of this differential expression in the adult nervous system.     

Cortical reorganization in training.

Plasticity within the human central motor system occurs and has been studied with transcranial magnetic stimulation in patients with amputations, spinal cord injuries, and ischemic nerve block. These studies have identified a pattern of motor system reorganization that results in enlarged muscle representation areas and large motor evoked potentials (MEPs) for muscles immediately proximal to the lesion. Some of these changes are apparent minutes after ischemic nerve block, weeks after spinal cord injury, and as early as six months after amputation.These studies motivated us to study the cortical motor reorganization after finger movement training in normals and after anastomosis of intercostal nerves to the musculocutaneous nerve in young patients with cervical root avulsions due to a traumatic motorcycle injury.     

Establishment and assessment of a simple and easily reproducible incision model of spinal cord neuron cells in vitro

A growing number of in vitro models have been introduced to study the mechanisms of spinal cord injury. A potential drawback of these models is that they are difficult to reproduce. In this study, an in vitro incision model was established using primary cultured neuronal cells from fetal rat spinal cords. The neurons were subjected to incision in a simple and reproducible way. To assess whether this model could simulate the responses of spinal cord neuron cells in vivo after a spinal cord transection, apoptosis, and the expression of immediate early genes were detected in the neurons at various time points after injury. The results indicated that: (1) significantly more terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were observed at 1, 3, and 7 d following injury and (2) the expression of both c-Jun and c-Fos was induced 10 min after incision and had markedly higher levels 2 h post-injury. These results suggested that our model can partially imitate the responses of in vivo neuronal cells after a spinal cord transection and such models may facilitate further understanding of biochemical and cellular events associated with spinal cord injury.     

Tyrosinated alpha-tubulin changes following epileptogenic and non-epileptogenic lesions in rat brain cortex

The expression of the tyrosinated isoform of alpha-tubulin was monitored in rat frontal cortex, in order to investigate the neuronal plasticity changes occurring either in a mirror focus or in a deafferented area. A mirror focus was triggered by epidural implantation of a cobalt gelatin disk in the contralateral left somatosensory area (group one). A deafferented area was obtained by surgical removal of the left frontal cortex (group two). All animals including controls underwent EcoG recordings immediately before killing (45, 60, 90 days post surgery). The right frontal cortex was removed from all the animals and processed with Western blot method. EcoG recordings revealed a paroxysmal activity in epileptic rats, whereas in rats with frontal deafferentation and controls, EcoG activity was normal. A significant increase in tyrosinated alpha-tubulin expression was detected both in the mirror focus (group one) and the "non-epileptic" deafferented frontal cortex (group two) in comparison with controls (group three). The transcallosal deafferentation, which is involved in both epileptogenic and non-epileptogenic lesions, is supposed to play a role in the mechanism responsible for the plasticity responses recorded in the cortical areas studied.