Motor Cortex Of Adult Rats Research Articles

454 Effects of Human Brain Organoid Age on Post-Transplant Growth in the Rat Motor Cortex

INTRODUCTION: Human brain organoids have potential to be used as a substrate for brain repair following injury, however the factors affecting survival and integration of transplanted organoids are unknown. We hypothesized that organoids transplanted at an earlier time point would result in improved survival and integration into the motor cortex because of their greater growth potential. METHODS: Human forebrain organoids at two timepoints (d20-25, d55-60) were transplanted into the motor cortex of adult rats following an aspiration injury. The first cohort was survived for 1 month post transplantation (MPT, n = 6); the second cohort was survived for 2 MPT (n = 16). Quantification of organoid volume and immunohistochemistry were performed. RESULTS: Survival of organoids post-transplantation was >90%. Pre-transplantation organoid size at d20-25 was significantly smaller than d55-60 (p < 0.0001). Average organoid volume 2 MPT was 1.04E + 10 µm3, significantly increased from 1435.4 µm3 pre-transplant (p = 0.0156). 2 MPT was correlated with more growth than 1MPT, though not statistically significant (p = 0.2672). Younger organoids trended toward a larger end-volume with the mean d20-25 volume being 3.1x larger than d55-60 at 1MPT (p = 0.3211) and 1.74x larger at 2MPT (p = 0.5090). Axon projections were seen in the adjacent host cortex at both timepoints. Both organoid age groups contained neural progenitors (PAX6, Sox2) with d20-25 retaining areas reminiscent of neural progenitor zones at 1MPT. CONCLUSIONS: Survival of transplanted organoids following injury was successful with a vast majority of organoids experiencing rapid growth within the injury cavity. Both age cohorts demonstrated adjacent axon projection and the presence of neural progenitors. Though further investigation is needed to clarify the influence of organoid maturity on integration, the survival rate and degree of post-transplant growth is a promising first step.

Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats.

Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student's t-test, considering p < 0.05. We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance.

Methylmercury intoxication and cortical ischemia: Pre-clinical study of their comorbidity

Stroke is one of the main causes of human disability worldwide. Ischemic stroke is mostly characterized by metabolic collapse and fast tissue damage, followed by secondary damage in adjacent regions not previously affected. Heavy metals intoxication can be associated with stroke incidence, because of their damaging action in the vascular system. Mercury, in particular, possesses a high tropism by metabolically active regions, such as the brain. In the present study we sought to evaluate whether methylmercury (MeHg) intoxication can aggravate the tissue damage caused by an ischemic stroke induced by microinjections of endothelin-1 (ET-1) into the motor cortex of adult rats. Following MeHg intoxication by gavage (0.04 mg/kg/day) during 60 days, the animals were injected with ET-1 (1 μl, 40 pmol/μl) or vehicle (1 μl). After 7 days, all animals were submitted to behavioral tests and then their brains were processed to biochemical and immunohistochemical analyses. We observed that long-term MeHg intoxication promoted a significant Hg deposits in the motor cortex, with concomitant increase of microglial response, followed by reduction of the neuronal population following ischemia and MeHg intoxication, as well as disturbance in the antioxidant defense mechanisms by misbalance of oxidative biochemistry with increase of both lipid peroxidation and nitrite levels, associated to behavioral deficits. MeHg exposure and cortical ischemia demonstrated that both injuries are able of causing significant neurobehavioural impairments in motor coordination and learning accompanied of an exacerbated microglial activation, oxidative stress and neuronal loss in the motor cortex, indicating that MeHg as a source of metabolic disturbance can act as an important increasing factor of ischemic events in the brain.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Functional remodeling of subtype-specific markers surrounding implanted neuroprostheses.

Microelectrode arrays implanted in the brain are increasingly used for the research and treatment of intractable neurological disease. However, local neuronal loss and glial encapsulation are known to interfere with effective integration and communication between implanted devices and brain tissue, where these observations are typically based on assessments of broad neuronal and astroglial markers. However, both neurons and astrocytes comprise heterogeneous cellular populations that can be further divided into subclasses based on unique functional and morphological characteristics. In this study, we investigated whether or not device insertion causes alterations in specific subtypes of these cells. We assessed the expression of both excitatory and inhibitory markers of neurotransmission (vesicular glutamate and GABA transporters, VGLUT1 and VGAT, respectively) surrounding single-shank Michigan-style microelectrode arrays implanted in the motor cortex of adult rats by use of quantitative immunohistochemistry. We found a pronounced shift from significantly elevated VGLUT1 within the initial days following implantation to relatively heightened VGAT by the end of the 4-wk observation period. Unexpectedly, we observed VGAT positivity in a subset of reactive astrocytes during the first week of implantation, indicating heterogeneity in early-responding encapsulating glial cells. We coupled our VGLUT1 data with the evaluation of a second marker of excitatory neurons (CamKiiα); the results closely paralleled each other and underscored a progression from initially heightened to subsequently weakened excitatory tone in the neural tissue proximal to the implanted electrode interface (within 40 μm). Our results provide new evidence for subtype-specific remodeling surrounding brain implants that inform observations of suboptimal integration and performance.NEW & NOTEWORTHY We report novel changes in the local expression of excitatory and inhibitory synaptic markers surrounding microelectrode arrays implanted in the motor cortex of rats, where a progressive shift toward increased inhibitory tone was observed over the 4-wk observation period. The result was driven by declining glutamate transporter expression (VGLUT1) in parallel with increasing GABA transporter expression (VGAT) over time, where a reactive VGAT+ astroglial subtype made an unexpected contribution to our findings.

Comparative effect of immature neuronal or glial cell transplantation on motor functional recovery following experimental traumatic brain injury in rats.

The present study evaluated the comparative effect of stereotaxically transplanted immature neuronal or glial cells in brain on motor functional recovery and cytokine expression after cold-induced traumatic brain injury (TBI) in adult rats. A total of 60 rats were divided into four groups (n=15/group): Sham group; TBI only group; TBI plus neuronal cells-transplanted group (NC-G); and TBI plus glial cells-transplanted group (GC-G). Cortical lesions were induced by a touching metal stamp, frozen with liquid nitrogen, to the dura mater over the motor cortex of adult rats. Neuronal and glial cells were isolated from rat embryonic and newborn cortices, respectively, and cultured in culture flasks. Rats received neurons or glia grafts (~1×106 cells) 5 days after TBI was induced. Motor functional evaluation was performed with the rotarod test prior to and following glial and neural cell grafts. Five rats from each group were sacrificed at 2, 4 and 6 weeks post-cell transplantation. Immunofluorescence staining was performed on brain section to identify the transplanted neuronal or glial cells using neural and astrocytic markers. The expression levels of cytokines, including transforming growth factor-β, glial cell-derived neurotrophic factor and vascular endothelial growth factor, which have key roles in the proliferation, differentiation and survival of neural cells, were analyzed by immunohistochemistry and western blotting. A localized cortical lesion was evoked in all injured rats, resulting in significant motor deficits. Transplanted cells successfully migrated and survived in the injured brain lesion, and the expression of neuronal and astrocyte markers were detected in the NC-G and GC-G groups, respectively. Rats in the NC-G and GC-G cell-transplanted groups exhibited significant motor functional recovery and reduced histopathologic lesions, as compared with the TBI-G rats that did not receive neural cells (P<0.05, respectively). Furthermore, GC-G treatment induced significantly improved motor functional recovery, as compared with the NC-G group (P<0.05). Increased cytokine expression levels were detected in the NC-G and GC-G groups, as compared with the TBI-G; however, no differences were found between the two groups. These data suggested that transplanted immature neural cells may promote the survival of neural cells in cortical lesion and motor functional recovery. Furthermore, transplanted glial cells may be used as an effective therapeutic tool for TBI patients with abnormalities in motor functional recovery and cytokine expression.

Peripheral nerve injury induces glial activation in primary motor cortex

Peripheral nerve injury induces glial activation in primary motor cortex

AAV vector-mediated secretion of chondroitinase provides a sensitive tracer for axonal arborisations

As part of a project to express chondroitinase ABC (ChABC) in neurons of the central nervous system, we have inserted a modified ChABC gene into an adeno-associated viral (AAV) vector and injected it into the vibrissal motor cortex in adult rats to determine the extent and distribution of expression of the enzyme. A similar vector for expression of green fluorescent protein (GFP) was injected into the same location. For each vector, two versions with minor differences were used, giving similar results. After 4 weeks, the brains were stained to show GFP and products of chondroitinase digestion. Chondroitinase was widely expressed, and the AAV-ChABC and AAV-GFP vectors gave similar expression patterns in many respects, consistent with the known projections from the directly transduced neurons in vibrissal motor cortex and adjacent cingulate cortex. In addition, diffusion of vector to deeper neuronal populations led to labelling of remote projection fields which was much more extensive with AAV-ChABC than with AAV-GFP. The most notable of these populations are inferred to be neurons of cortical layer 6, projecting widely in the thalamus, and neurons of the anterior pole of the hippocampus, projecting through most of the hippocampus. We conclude that, whereas GFP does not label the thinnest axonal branches of some neuronal types, chondroitinase is efficiently secreted from these arborisations and enables their extent to be sensitively visualised. After 12 weeks, chondroitinase expression was undiminished.

Complete reorganization of the motor cortex of adult rats following long‐term spinal cord injuries

Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats.

Modulation of microglial activation enhances neuroprotection and functional recovery derived from bone marrow mononuclear cell transplantation after cortical ischemia

Activated microglia may exacerbate damage in neural disorders; however, it is unknown how they affect stem cells transplanted after stroke. Focal ischemia was induced by microinjections of 40pmol of endothelin-1 into the motor cortex of adult rats. Ischemic animals were treated with sterile saline (n=5), bone marrow mononuclear cells (BMMCs, n=8), minocycline (n=5) or concomitantly with minocycline and BMMCs (n=5). BMMC-treated animals received 5×106BMMCs through the caudal vein 24h post-ischemia. Behavioral tests were performed to evaluate functional recovery. Morphometric and histological analyses were performed to assess infarct area, neuronal loss and microglia/macrophage activation up to 21days post-ischemia. Treatments with minocycline, BMMCs or minocycline-BMMCs reduced infarct area, increased neuronal survival and decreased the number of caspase-3+ and ED-1+ cells, but these effects were more prominent in the minocycline-BMMC group. Behavioral analyses using the modified sticky-tape and open-field tests showed that ischemic rats concomitantly treated with BMMCs and minocycline showed better motor performance than rats treated with BMMCs or minocycline only. The results suggest that proper modulation of the inflammatory response through the blockage of microglia activation enhances neuroprotection and functional recovery induced by intravenous transplantation of BMMCs after motor cortex ischemia.

Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury

The oil-resin of Copaifera reticulata Ducke is used in the Brazilian folk medicine as an anti-inflammatory and healing agent. However, there are no investigations on the possible anti-inflammatory and neuroprotective roles of copaiba oil-resin (COR) after neural disorders. We have investigated the anti-inflammatory and neuroprotective effects of COR following an acute damage to the motor cortex of adult rats. Animals were injected with the neurotoxin N-Methyl-D-Aspartate (NMDA) (n = 10) and treated with a single dose of COR (400 mg/kg, i.p.) soon after surgery (Group 1) or with two daily doses (200 mg/kg, i.p.) during 3 days (Group 2) alter injury. Control animals were treated with vehicle only. COR treatment induced tissue preservation and decreased the recruitment of neutrophils and microglial activation in the injury site compared to vehicle animals. The results suggest that COR treatment induces neuroprotection by modulating inflammatory response following an acute damage to the central nervous system.

In vivo biocompatibility and in vitro characterization of poly-lactide-co-glycolide structures containing levetiracetam, for the treatment of epilepsy

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy.

Embryonic amygdalar transplants in adult rats with motor cortex lesions: a molecular and electrophysiological analysis

Transplants of embryonic nervous tissue ameliorate motor deficits induced by motor cortex lesions in adult animals. Restoration of lost brain functions has been recently shown in grafts of homotopic cortical origin, to be associated with a functional integration of the transplant after development of reciprocal host–graft connections. Nevertheless little is known about physiological properties or gene expression profiles of cortical implants with functional restorative capacity but no cortical origin. In this study, we show molecular and electrophysiological evidence supporting the functional development and integration of heterotopic transplants of embryonic amygdalar tissue placed into pre-lesioned motor cortex of adult rats. Grafts were analyzed 3 months post-transplantation. Using reverse transcriptase quantitative polymerase chain reaction, we found that key glutamatergic, GABAergic, and muscarinic receptors transcripts were expressed at different quantitative levels both in grafted and host tissues, but were all continuously present in the graft. Parallel sharp electrode recordings of grafted neurons in brain slices showed a regular firing pattern of transplanted neurons similar to host amygdalar pyramidal neurons. Synaptic connections from the adjacent host cortex on grafted neurons were electrophysiologically investigated and confirmed our molecular results. Taken together, our findings indicate that grafted neurons from a non-cortical, non-motor-related, but ontogenetical similar source, not only received functionally effective contacts from the adjacent motor cortex, but also developed electrophysiological and gene expression patterns comparable to host pyramidal neurons; suggesting an interesting tool for the field of neural repair and donor tissue in adults.

Electrophysiological and Synaptic Characterization of Transplanted Neurons in Adult Rat Motor Cortex

Lesions in specific areas of the rat motor cortex generate deficits related to fine movement performance affecting the forelimb. We have previously shown that transplants of embryonic frontal cortex ameliorate these motor deficits. Amelioration has been associated with a functional integration of the transplant due to the connections established between the host brain and the graft. In the current investigation, the electrophysiological properties of the transplanted cells and the connections both intra-transplant and with the adjacent host cortex are analyzed. For this purpose, adult rats with a motor cortical lesion plus a fetal cortical graft were used. Neurons in the transplant were recorded using sharp electrodes or whole-cell recordings in brain slices. Application of intracellular depolarizing pulses showed two patterns of cell firing: regular and burst spiking. Postsynaptic responses evoked by both, intra-transplant and adjacent host cortex stimulation were mediated by glutamic acid acting on non-NMDA and NMDA receptors, and were modulated by both cholinergic and GABAergic drugs. In some cells, supra-threshold intra-transplant stimulation generated an epileptiform-like discharge, suggesting an imbalance between excitatory and inhibitory synapses. As expected, immunohistochemistry for cholinergic and GABAergic markers confirmed the electrophysiological results. Thus we show electrophysiological and immunohistochemical evidence supporting the functional development and integration of grafted cells into the host neocortex of adult animals.

In Vivo Electrical Impedance Spectroscopy of Tissue Reaction to Microelectrode Arrays

The goal of this experiment was to determine the electrical properties of the tissue reaction to implanted microelectrode arrays. We describe a new method of analyzing electrical impedance spectroscopy data to determine the complex impedance of the tissue reaction as a function of postimplantation time. A model is used to extract electrical model parameters of the electrode-tissue interface, and is used to isolate the impedance of the tissue immediately surrounding the microelectrode. The microelectrode arrays consist of microfabricated polyimide probes, incorporating four 50- mum-diameter platinum microelectrodes. The devices were implanted in the primary motor cortex of adult rats, and measurements were performed for 12 weeks. Histology was performed on implants at three time points in one month. Results demonstrate that the tissue reaction causes a rapid increase in bioimpedance over the first 20 days, and then stabilizes. This result is supported by histological data.

Focal Photothrombotic Lesion of the Rat Motor Cortex Increases BDNF Levels in Motor-Sensory Cortical Areas Not Accompanied by Recovery of Forelimb Motor Skills

Brain infarct triggers neurodegeneration that often shades spontaneous plasticity, occurring in the areas related anatomically and functionally to the infarcted structures. Neurotrophins which promote neuronal survival and plasticity, may protect neurons and enhance remodeling of the remaining circuits, leading to restoration of function. In particular, the crucial role of brain-derived neurotrophic factor (BDNF) in cortical function is well documented. Since BDNF was implicated in the mechanism of postinfarct recovery, we investigated whether focal photothrombosis in the motor cortex of adult rats modifies cortical BDNF protein levels in a time- and region-dependent fashion. In parallel, we aimed to establish, which cortical cells respond with altered BDNF expression and whether these alterations are reflected by forelimb motor skill impairment and recovery, evaluated up to 1 month postinfarct. The distribution of BDNF protein was visualized immunohistochemically and BDNF tissue levels were evaluated with enzyme-linked immunosorbent assay (ELISA). Ipsilateral to the infarct, an increase in BDNF levels occurred both in injured and neighboring regions already 24 h after photothrombosis. This increase was sustained up to postlesion day 7 in the motor cortex and reduced at 28 days. No BDNF changes were detected in homotopic regions of the contralateral cortex. The time-course of enhanced neurotrophic expression was paralleled by bilateral deficits in skilled reaching, which was the only clear and measurable motor impairment observed in the study. We conclude that the spontaneous increase of BDNF is not sufficient to protect neurons from degeneration in the lesion proximity whereas plasticity reported in the adjacent regions may be attributable to enhanced BDNF-related stimuli, which do not counteract the impairment of skilled reaching but might be, at least in part, responsible for the absence of deficits in other functional/behavioral tests.

Plastic changes in the vibrissa motor cortex in adult rats after output suppression in the homotopic cortex

After motor cortex damage, the unaffected homotopic cortex shows changes in motor output. The present experiments were designed to clarify the nature of these interhemispheric effects. We investigate the vibrissa motor cortex (VMC) output after activity suppression of the homotopic area in adult rats. Comparison was made of VMC output after lidocaine inactivation (L-group) or quinolinic acid lesion (Q-group) of the homotopic cortex. In the Q-group, VMC mapping was performed 3 days (Q3Ds group), 2 weeks (Q2Ws group) and 4 weeks (Q4Ws group) after cortical lesion. In each animal, VMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). Findings demonstrated that, in the L-group, the size of vibrissal representation was 39.5% smaller and thresholds required to evoke vibrissa movement were 46.3% higher than those in the Control group. There was an increase in the percentage of ineffective sites within the medial part of the VMC and an increase in the percentage of forelimb sites within the lateral part. Both the Q3Ds group and the L-group led to a similar VMC reorganization (Q3Ds vs. L-group, P > 0.05). In the Q2Ws group the VMC representation showed improvement in size (83.4% recovery compared with controls). The VMC showed recovery to normal output at 4 weeks after lesion (Control vs. Q4Ws group, P > 0.05). These results suggest that the VMC of the two hemispheres continuously interact through excitatory influences, preserving the normal output and inhibitory influences defining the border with the forelimb representation.

Motor cortical network oscillations driven by voltage‐ and ligand‐gated currents

Motor cortical network oscillations driven by voltage‐ and ligand‐gated currents

Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons.

BackgroundInflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.ResultsApplication of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.ConclusionInflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.

Time‐sensitive enhancement of motor learning with the less‐affected forelimb after unilateral sensorimotor cortex lesions in rats

Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) results in time-dependent changes in neuronal activity, structure and connectivity in the contralateral motor cortex of adult rats. These changes have been linked to facilitation of motor skill learning in the less-affected/ipsilesional forelimb, which is likely to promote its use in the development of behavioral compensation. The goal of this study was to determine whether an early post-lesion-sensitive time period exists for this enhanced learning and whether it is linked to synaptogenesis in the contralesional motor cortex. Rats were trained for 21 days on a skilled reaching task with the ipsilesional forelimb beginning 4 or 25 days after unilateral ischemic (endothelin-1-induced) FLsmc lesions or sham operations. As found previously, reaching performance was significantly enhanced in rats trained early post-lesion compared with sham-operates. In rats trained later post-lesion, performance was neither significantly different from time-matched sham-operates nor strikingly different from animals trained earlier post-lesion. In layer V of the contralesional motor cortex, stereological methods for light and electron microscopy revealed significantly more total, multisynaptic bouton and perforated synapses per neuron compared with sham-operates, but there were no significant differences between early- and late-trained lesion groups. Thus, there appears to be a sensitive time window for the maximal expression of the enhanced learning capacity of the less-affected forelimb but this window is broadly, rather than sharply, defined. These results indicate that relatively long-lasting lesion-induced neuronal changes are likely to underlie the facilitation of learning with the less-affected forelimb.