Differential involvement of rubral branches in chronic capsular and pontine stroke.

BACKGROUND AND PURPOSE: Early studies have indicated that the cortico-rubro-spinal tracts play important roles in motor dysfunction after stroke. However, the differential involvement of the rubral branches in capsular and pontine stroke, and their associations with the motor impairment are still unknown. METHODS: The present study recruited 144 chronic stroke patients and 91 normal controls (NC) from three hospitals, including 102 cases with capsular stroke (CS) and 42 cases with pontine stroke (PS). The rubral branches, including bilateral corticorubral tracts (CRT), dentatorubral tracts (DRT), and rubrospinal tracts (RST), and the cortico-spinal tract (CST) were reconstructed based on the dataset of the Human Connectome Project. Group differences in diffusion scalars of each rubral branch were compared, and the associations between the diffusion measures of rubral branches and the Fugl-Meyer assessment (FMA) scores were tested. RESULTS: The bilateral CRT of the CS cases showed significantly lower factional anisotropy (FA) than in the NC. The bilateral DRT of the PS cases had lower FA than in the NC. Both CS and PS cases had significantly lower FA of the bilateral RST than the NC. Besides, the stroke patients demonstrated significantly lower FA in bilateral CSTs than the NC. Partial correlation analysis identified significantly positive correlations between the FA of the ipsilesional and CRT and the FMA scores in the CS group, and significantly positive correlations between the FA of the RST bilaterally and the FMA scores in the CS and PS groups. Furthermore, the association between RST integrity and FMA scores still survived after controlling for the effect of the CST. Finally, multiple regression modelling found that rubral tract FA explained 39.2% of the variance in FMA scores for CS patients, and 48.8% of the variance in FMA scores for PS patients. CONCLUSIONS: The bilateral rubral branches were differentially involved in the chronic capsular and pontine stroke, and the impairment severity of each rubral branch was dependent on lesion locations. The integrity of the rubral branches is related to motor impairment in both the chronic capsular and pontine stroke.

Altered functional connectivity of the red nucleus and substantia nigra in migraine without aura.

BACKGROUND: Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. Accumulating evidence is pointing toward malfunctioning of brainstem structures, i.e., the red nucleus (RN) and substantia nigra (SN), as an important factor in migraine without aura (MwoA). We aimed to identify atypical FC between the RN and SN and other brain areas in patients with MwoA and to explore the association between RN and SN connectivity changes and performance on neuropsychological tests in these patients. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were obtained from 30 patients with MwoA and 22 age-, sex-, and years of education-matched healthy controls (HC). The FC of the brainstem structures was analyzed using a standard seed-based whole-brain correlation method. The results of the brainstem structure FC were assessed for correlations with other clinical features. RESULTS: Patients with MwoA exhibited reduced left RN-based FC with the left middle frontal gyrus, reduced right RN-based FC with the ipsilateral superior parietal lobe, and increased FC with the ipsilateral cerebellum. Additionally, patients with MwoA demonstrated significantly decreased right SN-based FC with the right postcentral gyrus, left parietal lobule, and left superior frontal gyrus. Hypo-connectivity between the right SN and right postcentral gyrus was negatively correlated with disease duration (r = - 0.506, P = 0.004). Additionally, increased connectivity of the right RN to the ipsilateral cerebellar lobes was positively correlated with the Headache Impact Test-6 scores (r = 0.437, P = 0.016). CONCLUSIONS: The present study suggested that patients with MwoA have disruption in their RN and SN resting-state networks, which are associated with specific clinical characteristics. The changes focus on the regions associated with cognitive evaluation, multisensory integration, and modulation of perception and pain, which may be associated with migraine production, feedback, and development. Taken together, these results may improve our understanding of the neuropathological mechanism of migraine.

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

Single-unit analysis of the human posterior hypothalamus and red nucleus during deep brain stimulation for aggressivity.

OBJECTIVE Deep brain stimulation (DBS) of the posterior hypothalamus (PH) has been reported to be effective for aggressive behavior in a number of isolated cases. Few of these case studies have analyzed single-unit recordings in the human PH and none have quantitatively analyzed single units in the red nucleus (RN). The authors report on the properties of ongoing neuronal discharges in bilateral trajectories targeting the PH and the effectiveness of DBS of the PH as a treatment for aggressive behavior. METHODS DBS electrodes were surgically implanted in the PH of 1 awake patient with Sotos syndrome and 3 other anesthetized patients with treatment-resistant aggressivity. Intraoperative extracellular recordings were obtained from the ventral thalamus, PH, and RN and analyzed offline to discriminate single units and measure firing rates and firing patterns. Target location was based on the stereotactic coordinates used by Sano et al. in their 1970 study and the location of the dorsal border of the RN. RESULTS A total of 138 units were analyzed from the 4 patients. Most of the PH units had a slow, irregular discharge (mean [± SD] 4.5 ± 2.7 Hz, n = 68) but some units also had a higher discharge rate (16.7 ± 4.7 Hz, n = 15). Two populations of neurons were observed in the ventral thalamic region as well, one with a high firing rate (mean 16.5 ± 6.5 Hz, n = 5) and one with a low firing rate (mean 4.6 ± 2.8 Hz, n = 6). RN units had a regular firing rate with a mean of 20.4 ± 9.9 Hz and displayed periods of oscillatory activity in the beta range. PH units displayed a prolonged period of inhibition following microstimulation compared with RN units that were not inhibited. Patients under anesthesia showed a trend for lower firing rates in the PH but not in the RN. All 4 patients displayed a reduction in their aggressive behavior after surgery. CONCLUSIONS During PH DBS, microelectrode recordings can provide an additional mechanism to help identify the PH target and surrounding structures to be avoided such as the RN. PH units can be distinguished from ventral thalamic units based on their response to focal microstimulation. The RN has a characteristic higher firing rate and a pattern of beta oscillations in the spike trains. The effect of the anesthetic administered should be considered when using microelectrode recordings. The results of this study, along with previous reports, suggest that PH DBS may be an effective treatment for aggression.

Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.

OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel-treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel-treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel-treated group. There was a decreased presence of inflammatory cells in the HA hydrogel-treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

Change of Neural Connectivity of the Red Nucleus in Patients with Striatocapsular Hemorrhage: A Diffusion Tensor Tractography Study.

The red nucleus (RN) is involved in motor control and it is known to have potential to compensate for injury of the corticospinal tract (CST). We investigated the change of connectivity of the RN (RNc) and its relation to motor function in patients with striatocapsular hemorrhage. Thirty-five chronic patients with striatocapsular hemorrhage were recruited. Motricity Index (MI), Modified Brunnstrom Classification (MBC), and Functional Ambulation Category (FAC) were measured for motor function. The probabilistic tractography method was used for evaluation of the RNc. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume (TV) of the RNc were measured. FA and TV ratios of the RNc in patients with discontinuation of the affected CST were significantly higher than those of patients with preserved integrity of the CST in the affected hemisphere (p < 0.05). TV ratio of the RNc showed significant negative correlation with upper MI (weak correlation, r = -0.35), total MI (weak correlation, r = -0.34), and MBC (moderate correlation, r = -0.43), respectively (p < 0.05). We found that the neural structure of the RNc was relatively increased in the unaffected hemisphere compared with the affected hemisphere in patients with more severe injury of the CST.

Targeting the red nucleus for cerebellar tremor.

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.

Etiology of impaired selective motor control: emerging evidence and its implications for research and treatment in cerebral palsy.

Selective motor control (SMC) impairment involves movement patterns dominated by flexor or extensor synergies that interfere with functional movements in children with cerebral palsy (CP). Emerging evidence on neural correlates of impaired SMC has important implications for etiology and for the treatment for children with CP. Early evidence on the microstructure of brain white matter assessed with diffusion tensor imaging in adult patients after stroke suggests that the rubrospinal tract may compensate for injury to the corticospinal tract. Furthermore, the observed changes on diffusion tensor imaging corresponded to the degree of SMC impairment. The rubrospinal tract may provide imperfect compensation in response to corticospinal tract injury, resulting in diminished SMC. Cortical mapping evidence in stroke patients indicates that loss of SMC is also associated with increased overlap of joint representation in the sensorimotor cortices. The severity of SMC impairment can be assessed with the recently developed Selective Control Assessment of the Lower Extremity, a validated observation-based measure designed for children with spastic CP. Recent advances in neuroimaging and assessment of SMC provide an opportunity to better understand the etiology and impact of impaired SMC, which may ultimately guide strategic treatment for children with CP.

Changes in red nucleus after pyramidal tract injury in patients with cerebral infarct.

We investigated red nucleus (RN) changes in patients with a cerebral infarct, using diffusion tensor imaging (DTI). Forty-nine consecutive stroke patients with pyramidal tract(PT) injury (mean age, 62.1 years; range, 41 to 75) and 46 age-matched normal healthy control subjects (mean age, 58.9 years; range, 41 to 75) with no history of neurologic disease were recruited. DTI was performed using a 1.5-T system during the early stage, after cerebral infarct (8-l21 days after onset). DTIs were acquired using a sensitivity-encoding head coil at 1.5 T. We measured fractional anisotropies (FAs) and apparent diffusion coefficients (ADCs) of RNs in the upper midbrain, and assessed the motor function of affected extremities. Mean FA of RNs in affected hemispheres was higher than in unaffected hemispheres (P < 0.05), however, no difference was observed between the unaffected control hemispheres (P> 0.05). However, mean ADC values of RNs were no different between control hemispheres and a patient's affected and unaffected hemispheres (P> 0.05). It appears that RN in affected hemispheres show elevated levels of neuronal activity during the early stage in patients with a corona radiata infarct, which suggests that RNs in affected hemispheres are used to compensate for PT injury.

Impaired axonal transport in motor neurons correlates with clinical prion disease.

Prion diseases are fatal neurodegenerative disorders causing motor dysfunctions, dementia and neuropathological changes such as spongiosis, astroglyosis and neuronal loss. The chain of events leading to the clinical disease and the role of distinct brain areas are still poorly understood. The role of nervous system integrity and axonal properties in prion pathology are still elusive. There is no evidence of both the functional axonal impairments in vivo and their connection with prion disease. We studied the functional axonal impairments in motor neurons at the onset of clinical prion disease using the combination of tracing as a functional assay for axonal transport with immunohistochemistry experiments. Well-established and novel confocal and ultramicroscopy techniques were used to image and quantify labeled neurons. Despite profound differences in the incubation times, 30% to 45% of neurons in the red nucleus of different mouse lines showed axonal transport impairments at the disease onset bilaterally after intracerebral prion inoculation and unilaterally -- after inoculation into the right sciatic nerve. Up to 94% of motor cortex neurons also demonstrated transport defects upon analysis by alternative imaging methods. Our data connect axonal transport impairments with disease symptoms for different prion strains and inoculation routes and establish further insight on the development of prion pathology in vivo. The alterations in localization of the proteins involved in the retrograde axonal transport allow us to propose a mechanism of transport disruption, which involves Rab7-mediated cargo attachment to the dynein-dynactin pathway. These findings suggest novel targets for therapeutic and diagnostic approaches in the early stages of prion disease.

Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats.

The purpose of this research was to investigate whether pathways in the dorsal part of the lateral spinal funiculus (DLF) can compensate for loss of corticospinal input (CST) to the spinal cord. The CST is known to control skilled limb movements in rats. The DLF contains several different pathways, including the rubrospinal tract (RST) which is also thought to influence limb movements. After lesions of either the corticospinal or the rubrospinal system, it is unclear how much of the remaining forelimb function is due to the presence of the alternate pathway. To begin to address this issue, the present study investigates the compensatory role of pathways in the DLF, including the rubrospinal tract, after bilateral lesions of the pyramidal tract (PT). We initially performed bilateral PT lesions in rats, which effectively removed the CST input to the spinal cord. We tested these rats during overground locomotion, skilled locomotion and skilled forelimb usage. After a 6 week recovery period, we then performed bilateral DLF lesions and compared the behavioural abilities of these rats to those of animals which underwent simultaneous PT and DLF lesions. If DLF pathways do compensate for PT lesions, then animals with PT lesions would rely more on DLF pathways than animals without PT lesions. Thus we hypothesized that animals with DLF lesions which were performed 6 weeks after PT lesions would exhibit more deficits on several behavioural tasks compared to animals which received PT and DLF lesions simultaneously. Our hypothesis was supported only for skilled pellet retrieval. Hence some DLF pathways, including the RST, were able to compensate for loss of CST input during skilled reaching but not during overground or skilled locomotion in PT-lesioned rats. These differential responses suggest that behavioural tasks vary in their reliance on specific pathways after injury, and, furthermore, that compensation for loss of specific connections can arise from numerous sources.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Undesired effects of a combinatorial treatment for spinal cord injury--transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus.

Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration-associated genes. Cell body treatment with brain-derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration-associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a cervical dorsolateral funiculus crush. Each treatment alone as well as their combination prevented the dieback of the rubrospinal axons, but none of them promoted rubrospinal regeneration beyond the lesion/transplantation site. Motor performance in a food-pellet reaching test and forelimb usage during vertical exploration (cylinder test) were more impaired after combining transplantation of OECs with BDNF treatment. This impaired motor performance correlated with lowered sensory thresholds in animals receiving the combinatorial therapy - which were not seen with each treatment alone. Only this combinatorial treatment group showed enhanced sprouting of calcitonin gene-related peptide-positive axons rostral to the lesion site. Hence, some combinatorial treatments, such as OECs with BDNF, may have undesired effects in the injured spinal cord.

Neuronal activity of the red nucleus in Parkinson's disease.

Precise placement of the electrodes for stimulation of the subthalamic nucleus (STN) in Parkinson's disease (PD) is crucial for the therapeutic benefit. As a result of the mistargeting and misplacement of the electrodes during surgery in 2 patients with PD, we have characterized the neuronal firing in the red nucleus (RN) and observed the effects of stimulation of this nucleus. Although the neuronal firing (mean +/- SD) of the RN (34 +/- 4.4 Hz) resembles that described for the STN (33.1 +/- 16.6 Hz), a higher proportion of cells responded to the movement of the contralateral limbs (70-80%). Stimulation in the area of the RN-induced intolerable side effects without motor improvement. We conclude that the STN and RN have some similar neurophysiological features but can be distinguished intraoperatively. This initial description of the physiological characteristics of the RN in humans will draw attention to the possibility of confusing the RN and STN during intraoperative recording.

Interleukin-1 beta of Red nucleus involved in the development of allodynia in spared nerve injury rats.

Previous studies have indicated that interleukin-1 beta (IL-1 beta) is involved not only in immune modulation, but also in the modulation of pain in both the peripheral and central nervous systems. The current study investigated the expression of IL-1 beta in the brain of rats with spared nerve injury (SNI), using immunohistochemical technique. The results showed that immunoreactive-like IL-1 beta protein was significantly elevated in the Red nucleus (RN) 2 weeks after SNI. To further study the function of IL-1 beta in RN, different doses of IL-1 beta neutralizing antibody (10, 1.0 and 0.1 ng) were microinjected into the RN contralateral to the nerve injury side of neuropathic rats. The results indicated that the higher doses of anti-IL-1 beta antibody (10 and 1.0 ng) significantly attenuated the mechanical allodynia of neuropathic rats. However, administration of 0.1 ng anti-IL-1 beta antibody did not show anti-allodynia effect. These results suggest that IL-1 beta of RN is involved in the development of neuropathic pain in SNI rats.

Expression of Semaphorin3C in axotomized rodent facial and rubrospinal neurons.

Semaphorins are a family of axonal guidance molecules that, by virtue of their chemorepulsive or chemoattractive actions, may be the important factors in determining the success or failure of axonal regeneration in the mature nervous system after injury. Here, we have used two adult mouse models of nervous system injury to evaluate the neuronal expression of Semaphorin3C (Sema3C) in regenerating (facial motoneurons) and non-regenerating (rubrospinal) neurons following axonal injury. Using in situ hybridization (ISH), we observed that uninjured facial motoneurons express Sema3C mRNA and, following axonal injury, there is a transient up-regulation in Sema3C mRNA expression in injured motoneurons. In contrast, Sema3C mRNA was not detected in uninjured rubrospinal neurons; however, following axotomy, injured rubrospinal neurons significantly up-regulate Sema3C mRNA expression. The increase in Sema3C mRNA expression in axotomized rubrospinal neurons was not limited to the mouse nervous system: serial dilution RT-PCR analysis revealed a similar increase in Sema3C mRNA expression in the axotomized rat rubrospinal nucleus, 3 days following a rubrospinal tract lesion. This demonstrates that increased Sema3C mRNA levels in axotomized rubrospinal neurons is common to both mouse and rat injury models.

Clinical and imaging characterization of a patient with idiopathic progressive ataxia and palatal tremor.

We describe clinical and imaging features of a patient with sporadic progressive ataxia and palatal tremor (PAPT) of unknown etiology. There was hypertrophy of bilateral inferior olivary nuclei with hyperintense T2-weighted signal and mild cerebellar atrophy at brain magnetic resonance imaging. 18F-fluoro-2-desoxy-d-glucose positron emission tomography scanning (FDG-PET) showed hypometabolism in the red nucleus, external globus pallidus and precuneus while FP-CIT-SPECT imaging revealed mild and progressive loss of striatal dopaminergic terminals. Our findings suggest that in idiopathic PAPT involvement of the dentato-rubro-olivary pathway occurs along with some dopaminergic dysfunction.

Neuroanatomical substrates for paroxysmal dyskinesia in lethargic mice.

The paroxysmal dyskinesias are a group of neurological disorders described by intermittent attacks of involuntary abnormal movements superimposed on a relatively normal baseline. The neuroanatomical substrates for these attacks are not fully understood, though available evidence from studies of affected people and animal models points to dysfunction in the basal ganglia or cerebellum. In the current studies, the anatomical basis for paroxysmal dyskinesias in lethargic mice was determined via histochemical methods sensitive to changes in regional brain activity followed by surgical elimination of the suspected source. Cytochrome oxidase histochemistry revealed increased activity in the red nucleus. Surgical removal of the cerebellum worsened ataxia but eliminated paroxysmal dyskinesias. These studies support the hypothesis that abnormal cerebellar output contributes to paroxysmal dyskinesias.

Class A plexin expression in axotomized rubrospinal and facial motoneurons.

The semaphorin family of guidance molecules plays a role in many aspects of neural development, and more recently semaphorins have been implicated to contribute to the failure of injured CNS neurons to regenerate. While semaphorin expression patterns after neural injury are partially understood, little is known about the expression of their signal transducing transmembrane receptors, the plexins. Therefore, in this study, we compared the expression patterns of all class A plexins (Plxn-A1, A2, A3, A4) in mouse CNS (rubrospinal) and peripheral nervous system (PNS)-projecting (facial) motoneurons for up to two weeks following axonal injury. Using in situ hybridization, immunohistochemistry, and Western blot analysis, in rubrospinal neurons, Plxn-A1 mRNA and protein and Plxn-A4 expression did not change as a result of injury while Plxn-A2 mRNA increased and Plxn-A3 mRNA was undetectable. In facial motoneurons, Plxn-A1, -A3 and -A4 mRNA expression increased, Plxn-A2 mRNA decreased while Plxn-A1 protein expression did not change following injury. We demonstrate that with the exception of the absence of Plxn-A3 mRNA in rubrospinal neurons, both injured rubrospinal (CNS) and facial (PNS) neurons maintain expression of all plexin A family members tested. Hence, there are distinct expression patterns of the individual plexin-A family members suggesting that regenerating rubrospinal and facial motoneurons have a differential ability to transduce semaphorin signals.