Ventral Funiculus Research Articles

Orexinergic Modulation of Spinal Motor Activity in the Neonatal Mouse Spinal Cord.

The role of orexin during development, and especially in terms of spinal cord function, is not well understood. It is for this reason that we focused on the network actions of orexin during the first week of development. We found that orexinergic fibers were present in the lumbar spinal cord of postnatal day 0 (P0) to P3 mice. The fibers were expressed mainly in the dorsal horn, but occasional fibers were observed in the ventral horn. Both orexin (OX) A and OXB increased the motoneurons (MNs) tonic neurogram discharge. However, only OXA was found to significantly increase spontaneous bursting activity and the frequency of fictive locomotor bursts. We show that OXA is able to act directly on MNs. To test the contribution of the recurrent MN collaterals, we blocked the nicotinic cholinergic drive and observed that OXA retained its ability to increase fictive locomotor activity. Additionally, we recorded neurograms from ventral lateral funiculi, where OXA had no effect on population discharge. These effects were also confirmed by recording from descending commissural interneurons via patch recordings. The loci of the effects of OXA were further investigated in a dorsal horn-removed preparation where OXA also shows an increase in the discharge from ventral root neurograms but no increase in the frequency of spontaneous or fictive locomotion burst activity. In summary, multiple lines of evidence from our work demonstrate the robust effects of orexins on spinal cord networks and MNs at the time of birth.

Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons by treatment with adult mesenchymal stem cells

BackgroundTreatment of spinal cord injury is dependent on neuronal survival, appropriate synaptic circuit preservation, and inflammatory environment management. In this sense, mesenchymal stem cell (MSC) therapy is a promising tool that can reduce glial reaction and provide trophic factors to lesioned neurons.MethodsLewis adult female rats were submitted to a unilateral ventral funiculus cut at the spinal levels L4, L5, and L6. The animals were divided into the following groups: IA (intramedullary axotomy), IA + DMEM (Dulbecco’s modified Eagle’s medium), IA + FS (fibrin sealant), IA + MSC (106 cells), and IA + FS + MSC (106 cells). Seven days after injury, qPCR (n = 5) was performed to assess gene expression of VEGF, BDNF, iNOS2, arginase-1, TNF-α, IL-1β, IL-6, IL-10, IL-4, IL-13, and TGF-β. The cellular infiltrate at the lesion site was analyzed by hematoxylin-eosin (HE) staining and immunohistochemistry (IH) for Iba1 (microglia and macrophage marker) and arginase-1. Fourteen days after injury, spinal alpha motor neurons (MNs), evidenced by Nissl staining (n = 5), were counted. For the analysis of astrogliosis in spinal lamina IX and synaptic detachment around lesioned motor neurons (GAP-43-positive cells), anti-GFAP and anti-synaptophysin immunohistochemistry (n = 5) was performed, respectively. Twenty-eight days after IA, the gait of the animals was evaluated by the walking track test (CatWalk; n = 7).ResultsThe site of injury displayed strong monocyte infiltration, containing arginase-1-expressing macrophages. The FS-treated group showed upregulation of iNOS2, arginase-1, proinflammatory cytokine (TNF-α and IL-1β), and antiinflammatory cytokine (IL-10, IL-4, and IL-13) expression. Thus, FS enhanced early macrophage recruitment and proinflammatory cytokine expression, which accelerated inflammation. Rats treated with MSCs displayed high BDNF-positive immunolabeling, suggesting local delivery of this neurotrophin to lesioned motoneurons. This BDNF expression may have contributed to the increased neuronal survival and synapse preservation and decreased astrogliosis observed 14 days after injury. At 28 days after lesion, gait recovery was significantly improved in MSC-treated animals compared to that in the other groups.ConclusionsOverall, the present data demonstrate that MSC therapy is neuroprotective and, when associated with a FS, shifts the immune response to a proinflammatory profile.

Three Dimensional Identification of Medial and Lateral Vestibulospinal Tract in the Human Brain: A Diffusion Tensor Imaging Study.

Purpose: The vestibulospinal tract (VST) is involved in balance control and gait function. No research has identified the VST in the human brain. In the current study, we attempted to identify the medial and lateral VST in the human brain, using diffusion tensor tractography (DTT).Materials and Methods: We recruited 40 healthy volunteers for this study. For reconstruction of the medial VST, a seed region of interest (ROI) was placed on the medial vestibular nuclei in the pons and target ROI on the posteromedial medulla. For reconstruction of the lateral VST, a seed ROI was placed on the lateral vestibular nuclei of pons and the target ROI on the posterolateral medulla. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of the medial and lateral VST were measured.Results: The medial VST, which originates from the medial vestibular nuclei, descends through the posteromedial medulla, and terminates at the anterior funiculus of the cervical spinal cord. The lateral VST originates from the lateral vestibular nuclei, and terminates in the anterior portion of lateral funiculus, through the posterolateral medulla. The FA value of medial VST was significantly higher than that of lateral VST. In contrast, the MD value and tract volume were significantly lower than those of lateral VST (p < 0.05).Conclusion: We identified the medial and lateral VST in the human brain using DTT and investigated the anatomical characteristics of the medial and lateral VST. The methodology and results of this study could be helpful to both clinicians and researchers in the neuroscience field.

Diffusion tensor imaging of spinal cord parenchyma lesion in rat with chronic spinal cord injury

PurposeAdequate evaluation of spinal cord parenchyma and accurate identification of injury range are considered two premises for the research and treatment of chronic spinal cord injury (SCI). Diffusion tensor imaging (DTI) provides information about water diffusion in spinal cord, and thus makes it possible to realize these premises. MethodIn this study, we conducted magnetic resonance imaging (MRI) for Wistar rats 84days after spinal cord contusion. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) from different positions of the injured cord were collected, analyzed, and compared with the histological results and locomotor outcomes. Moreover, we performed fiber tractography, and examined the difference in cavity percentage obtained respectively via conventional MRI, DTI and histology. ResultsResults showed that the chronic SCI rats had the largest changes of all DTI metrics at the epicenter; the farther away from the epicenter, the smaller the variation. FA, AD and RD were all influenced by SCI in a greater space range than MD. The good consistency of FA values and histological results in specific regions evidenced FA's capability of reflecting Wallerian degeneration after SCI. DTI metrics at the epicenter in ventral funiculus also showed a close correlation with the BBB scores. Additionally, supported by the histological results, DTI enables a more accurate measurement of cavity percentage compared to the conventional MRI. ConclusionDTI parameters might comprehensively reflect the post-SCI pathological status of spinal cord parenchyma at the epicenter and distal parts during the chronic stage, while showing good consistency with locomotor performance. DTI combined with tractography could intuitively display the distribution of spared fibers after SCI and accurately provide information such as cavity area. This may shed light on the research and treatment of chronic SCI.

Longitudinal electrophysiological changes after cervical hemi-contusion spinal cord injury in rats.

To evaluate the longitudinal somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) characterization from acute to chronic injury following cervical hemi-contusion spinal cord injury (SCI) in rats, and correlate the MEPs & SEPs to the behavioral outcomes. Fifteen adult male Sprague-Dawley rats were subjected to the hemi-contusion spinal cord injury at C5. Forelimb MEPs & SEPs were applied to 5 animals before injury and 3h, 1d, 3d, 1w, 2w, 4w and 8w after injury respectively. Forelimb functional assessments, including Montoya staircase task and cylinder rearing test, were conducted on another 10 animals before injury and at 2w, 4w and 8w after injury respectively, as well as histological analysis of the cord at 8w after injury. A group correlation was performed between the MEPs & SEPs and behavioral outcomes. The hemi-contusion injury resulted in unilateral tissue damage at the epicenter with loss of the ventral horns and lateral funiculus. Both ipsilateral and contralateral forelimb MEPs showed latency prolongation and amplitude reduction at 3h after injury. The MEPs amplitude increased with time after injury, but the ipsilateral amplitude was persistently lower than the contralateral amplitude. The ipsilateral MEPs latency increased with time after injury and was significantly longer than the contralateral MEPs latency. The ipsilateral SEPs amplitude dropped after injury and stayed at a lower level up to 8 weeks. There was no difference in the SEPs latency among time points and between sides. At 8 weeks after injury, the ipsilateral forelimb grasped 30% pellets while the contralateral forelimb close to 81%. An obvious decreased usage of the ipsilateral paw and increased usage of the contralateral paw were observed in rearing test after injury. The MEPs latency and amplitude correlated significantly with the forelimb motor function. Cervical hemi-contusion SCI led to persistent changes in MEPs & SEPs of the ipsilateral forelimb, ipsilateral impairment in motor function and unilateral cord tissue damage. Reliable electrophysiology assessment was obtained in chronic phase due to unstable MEPs & SEPs of bilateral forelimb immediately after injury, which might reflect the underlying pathological processes. The present study further confirmed the link of the MEPs to the behavioral outcomes, supporting the longitudinal electrophysiology assessment for neurological impairment after SCI.

Evaluation of DTI Parameter Ratios and Diffusion Tensor Tractography Grading in the Diagnosis and Prognosis Prediction of Cervical Spondylotic Myelopathy.

Prospective cohort. To explore the correlations between diffusion tensor imaging (DTI) ratios and diffusion tensor tractography (DTT) grading with clinical symptoms and outcomes of cervical spondylotic myelopathy (CSM). In addition to magnetic resonance imaging (MRI) and computed tomography, DTI may be useful in understanding pathophysiology of spinal cord in earlier stages of the CSM but it may be confounded by age and cervical level, and previous studies had small sample sizes. Controls (n = 36) and patients with CSM (n = 93) underwent magnetic resonance imaging (MRI) and DTI at the Changhai Hospital of Shanghai between September 2011 and March 2013. Apparent diffusion coefficient (ADC), fractional anisotropy (FA) of white matter (WM), and central grey matter (GM) were assessed. Patients were divided into three MRI grades: no abnormal signals; increased T2WI; and increased T2WI and low T1WI. DTT images were divided into three grades: no abnormal signals; abnormal local signal cord and disordered fiber tracts; and distortion of the spinal cord and interrupted fiber tracts. FA and ADC both correlated with age in all three bilateral WM funiculi and GM, whereas FA and ADC ratios only showed correlation with age in the ventral funiculus (VF) and central GM. Differences were observed in ADC ratios and FA ratios from different Japanese Orthopedic Association (JOA) score subgroups and JOA recovery subgroups. For the three WM funiculi and GM, correlations between DTI ratios, JOA scores, and JOA recovery rates were consistently higher than those between DTI values, JOA scores, and JOA recovery rates (all P < 0.05). MRI grading was correlated with the JOA scores (r = -0.674, P < 0.001) but not JOA recovery rates (r = -0.197, P = 0.058), whereas DTT grading was correlated with both JOA scores (r = -0.813, P < 0.001) and JOA recovery rate (r = -0.429, P < 0.001). DTI parameter ratios seemed to be less influenced by age than raw DTI results and could be more valuable than absolute DTI parameters for the evaluation of CSM. DTT grading is more valuable than MRI grading for diagnosis and prognostic prediction in CSM patients. 3.

Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.

In this study, we examined the efficacy of human umbilical cord blood mononuclear cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using adenoviral vectors, on posttraumatic regeneration after transplantation into the site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by transplantation of nontransduced hUCB-MCs, we observed an improvement in H (latency period, LP) and M(Amax) waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M wave and LP of both the M and H waves. The ratio between Amax of the H and M waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs. Spared tissue and myelinated fibers were increased at day 30 after SCI and transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF and GNDF genes significantly increased the number of spared myelinated fibers (22-fold, P > 0.01) in the main corticospinal tract compared to the nontransduced ones. HNA+ cells with the morphology of phagocytes and microglia-like cells were found as compact clusters or cell bridges within the traumatic cavities that were lined by GFAP+ host astrocytes. Our results show that hUCB-MCs transplanted into the site of SCI improved regeneration and that hUCB-MCs genetically modified with the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.

Shaping the Output of Lumbar Flexor Motoneurons by Sacral Neuronal Networks.

Spinal central pattern generators (CPGs) produce the rhythmic output required for coordinating stepping and stabilizing the body axis during movements. Electrical stimulation and exogenous drugs can reactivate the spinal CPGs and improve the motor function in the absence of descending supraspinal control. Since the body-stabilizing sacral networks can activate and modulate the limb-moving lumbar circuitry, it is important to clarify the functional organization of sacral and lumbar networks and their linking pathways. Here we decipher the ascending circuitry linking adrenoceptor-activated sacral CPGs and lumbar flexor motoneurons, thereby providing novel insights into mechanisms by which sacral circuitry recruits lumbar flexors, and enhances the motor output during lumbar afferent-induced locomotor rhythms. Moreover, our findings might help to improve drug/electrical stimulation-based therapy to accelerate locomotor-based rehabilitation.

New Xymedon Analogues for Stimulation of Posttraumatic Regeneration of the Spinal Cord in Rats

Effect of systemic administration of synthetic pyrimidine derivatives, xymedon and compounds 29D and 34D, was studied in rats with experimental dosed contusion spinal cord injury. Xymedon promoted recovery of motor function after injury. Compounds 29D and 34D more effectively restored the parameters of open-field and Rotarod tests in comparison with xymedon. Compound 29D more effectively than xymedon maintained the number of Olig2+ oligodendrocytes in the corticospinal tract and NG2 cells in all investigated areas of the white matter. In the group treated with compound 34D, the differences in the number of NG2+ cells were revealed only in the anterior funiculi, where the number of these glial cells was 2-fold higher than in the xymedon-treated group. Obtained results suggest that the studied xymedon analogs, compounds 29D and 34D, can exert their therapeutic action through different molecular and cellular pathways.

Changes in the Expression of FUS/TLS in Spinal Cords of SOD1 G93A Transgenic Mice and Correlation with Motor-Neuron Degeneration.

In order to searching the possible pathogenesis of amyotrophic lateral sclerosis (ALS), we examined the expression and distribution of FUS/TLS protein in the different anatomic regions, segments and neural cells of adult spinal cord at the different stages of the SOD1 wild-type and G93A transgenic mice using the fluorescent immunohistochemistry. Result revealed that, in the SOD1 wild-type mice, the FUS/TLS expression almost wasn't detected. However, in the SOD1 G93A mice, the FUS/TLS expression in the white matter was significantly more than that in the gray matter. In the white matter, the FUS/TLS expression in the anterior funiculus was more than that in the lateral funiculus more than that in the posterior funiculus. In the gray matter, the FUS/TLS expression in the ventral horn was more than that surrounding the central canal more than that in the dorsal horn. The FUS/TLS expression in the thoracic segment was more than that in the cervical segment more than that in the lumbar segment. Almost all FUS/TLS expressed in the nuclear of the GFAP positive cell at the onset stage, but it expressed in both the nuclear and the cytoplasm of the GFAP positive cell at the progression stage, almost didn't detected FUS/TLS expression in the NeuN and Oligo positive cells. The FUS/TLS expression was positively correlated with the neuron death. Our data suggested that the expressive increase and mislocalization of FUS/TLS in the astrocyte cell might cause the motor neuron degenerative death in the SOD1 G93A transgenic mice.

Histopathological and immunohistochemical study of spinal cord tissues in neurodegenerative diseases

To investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases. Spinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study, including 3 cases of multiple system strophy, 4 cases of amyotrophic lateral sclerosis, 5 cases of Alzheimer's disease (AD, included 2 cases of AD combined with Parkinson's disease), 2 cases of progressive supranuclear palsy, 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People's Liberation Army General Hospital. Four normal control cases were also included. Routine HE and Gallyas-Braak staining, and immunohistochemical stainings for anti-PHF tau (AT8), anti-α-synuclein, anti-TDP-43 and anti-ubiquitin were performed. Examination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf's nucleus of the sacral segment, along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments. Large amount of argentophilic, ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord. Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis, 2 of which were found with Bunina bodies in neurons of the anterior horn. Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments. A few argentophilic, tau positive neurofibrillary tangles (NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases. Examination of spinal cord in 2 cases with Parkinson's disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment, and a few synuclein positive lewy bodies and neuritis were also observed. There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic, tau positive globous NFTs and many argentophilic, tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case. Each common neurodegenerative diseases of the spinal cord including multiple system strophy, amyotrophic lateral sclerosis and Parkinson's disease has its own specific histopathology and proteinopathy characteristics.

Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

Neonatal white matter injury (nWMI) is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P) 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2–3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life, followed by dysmyelination, abnormal spinal neuron composition, and neuro-motor deficits in adulthood.

Termination of vestibulospinal fibers arising from the spinal vestibular nucleus in the mouse spinal cord

The present study investigated the vestibulospinal system which originates from the spinal vestibular nucleus (SpVe) with both retrograde and anterograde tracer injections. We found that fluoro-gold (FG) labeled neurons were found bilaterally with a contralateral predominance after FG injections into the upper lumbar cord. Anterogradely labeled fibers from the rostral SpVe traveled in the medial part of the ventral funiculus ipsilaterally and the dorsolateral funiculus bilaterally in the cervical cord. They mainly terminated in laminae 5–8, and 10 of the ipsilateral spinal cord. The contralateral side had fewer fibers and they were found in laminae 6–8, and 10. In the thoracic cord, fibers were also found to terminate in bilateral intermediolateral columns. In the lumbar and lower cord, fibers were mainly found in the dorsolateral funiculus bilaterally and they terminated predominantly in laminae 3–7 contralaterally. Anterogradely labeled fibers from the caudal SpVe did not travel in the medial part of the ventral funiculus but in the dorsolateral funiculus bilaterally. They mainly terminated in laminae 3–8 and 10 contralaterally. The present study is the first to describe the termination of vestibulospinal fibers arising from the SpVe in the spinal cord. It will lay the anatomical foundation for those who investigate the physiological role of vestibulospinal fibers and potentially target these fibers during rehabilitation after stroke, spinal cord injury, or vestibular organ injury.

Terminations of reticulospinal fibers originating from the gigantocellular reticular formation in the mouse spinal cord.

The present study investigated the projections of the gigantocellular reticular nucleus (Gi) and its neighbors--the dorsal paragigantocellular reticular nucleus (DPGi), the alpha/ventral part of the gigantocellular reticular nucleus (GiA/V), and the lateral paragigantocellular reticular nucleus (LPGi)--to the mouse spinal cord by injecting the anterograde tracer biotinylated dextran amine (BDA) into the Gi, DPGi, GiA/GiV, and LPGi. The Gi projected to the entire spinal cord bilaterally with an ipsilateral predominance. Its fibers traveled in both the ventral and lateral funiculi with a greater presence in the ventral funiculus. As the fibers descended in the spinal cord, their density in the lateral funiculus increased. The terminals were present mainly in laminae 7-10 with a dorsolateral expansion caudally. In the lumbar and sacral cord, a considerable number of terminals were also present in laminae 5 and 6. Contralateral fibers shared a similar pattern to their ipsilateral counterparts and some fibers were seen to cross the midline. Fibers arising from the DPGi were similarly distributed in the spinal cord except that there was no dorsolateral expansion in the lumbar and sacral segments and there were fewer fiber terminals. Fibers arising from GiA/V predominantly traveled in the ventral and lateral funiculi ipsilaterally. Ipsilaterally, the density of fibers in the ventral funiculus decreased along the rostrocaudal axis, whereas the density of fibers in the lateral funiculus increased. They terminate mainly in the medial ventral horn and lamina 10 with a smaller number of fibers in the dorsal horn. Fibers arising from the LPGi traveled in both the ventral and lateral funiculi and the density of these fibers in the ventral and lateral funiculi decreased dramatically in the lumbar and sacral segments. Their terminals were present in the ventral horn with a large portion of them terminating in the motor neuron columns. The present study is the first demonstration of the termination pattern of fibers arising from the Gi, DPGi, GiA/GiV, and LPGi in the mouse spinal cord. It provides an anatomical foundation for those who are conducting spinal cord injury and locomotion related research.

Dynamic expression of ATF3 as a novel tool to study activation and migration of endogenous spinal stem cells and their role in neural repair.

One of the major problems of modern neurobiology is how to replace dead or damaged neurons in the human brain or spinal cord after injury or as a consequence of neurodegenerative diseases. In fact, because adult mammalian neurons are post-mitotic cells that cannot divide to replace dead cells, loss due to lesion or disease is permanent. Furthermore, surviving neurons have modest capacity to regenerate their damaged axons and re-establish functional connections. Thus, a gradual neurodegenerative scenario with certain similarities in stroke, brain or spinal cord injuries and neurological diseases like Alzheimer's disease is produced. These conditions represent the major disease burden of the modern world in terms of mortality, disability, productivity loss and health-care costs (World Health Organization, 2008). While much effort has been directed to understand the molecular and cellular mechanisms involved in the pathology of these diseases to set new effective treatments, many neuroprotective and regenerative approaches, although showing positive results in preclinical studies, have so far failed to provide strong benefit to patients.

Value of magnetic resonance diffusion tensor imaging ratios in evaluating clinical symptoms and prognosis of cervical spondylotic myelopathy

Objective To explore the value of the apparent diffusion coefficient(ADC)ratio and fractional anisotropy(FA)ratio of magnetic resonance(MR)diffusion tensor imaging(DTI)in evaluating the clinical symptoms,prognosis of cervical spondylotic myelopathy(CSM).Methods Thirty-six healthy subjects and fifty CSM patients were involved and received MRI examination.Regions of interest(ROIs)were selected in the ventral funiculus(VF),lateral funiculi(LF),dorsal funiculus(DF),and central gray matter(GM)for ADC and FA measurements.In the control group,ADC and FA ratios were calculated using the original values at the C3/4,C4/5,C5/6,and C6/7levels to divide the corresponding values at their C1/2levels.In the CSM group,ADC and FA ratios were calculated using the ADC and FA values at the most compressed levels to divide the corresponding values at their C1/2levels.In the control group,the variances of the two ratios were compared between different cervical levels and ages.CSM patients were divided into mild,moderate,and severe group according to the preoperative Japanese Orthopaedic Association(JOA)scoring system,and were divided into well,moderate,and poor group according to the postoperative JOA recovery rates.Correlations between DTI parameters,DTI ratios of the VF,LF,DF,and GM of the CSM patients and the JOA scores,JOA recovery rates were assessed among different clinical symptom subgroups and prognosis subgroups.Results In control group,DTI ratios(ADC ratios and FA ratios)in VF,LF,DF,and GM were significantly different between C3/4,C4/5,C5/6,and C6/7levels(P0.05),but not found between different age subgroups.Correlations between DTI ratios of the VF,LF,DF,and GM and JOA scores,JOA recovery rates were significantly superior than the correlations between DTI parameters and JOA scores,JOA recovery rates(P0.05 or P0.01),with the FA ratio being superior to the ADC ratio.Compared with normal control group,the ADC ratios increased gradually in order and FA ratios decreased gradually in the mild,moderate,and severe injury subgroups(P0.05).Compared with normal control group,the ADC ratios increased gradually in order and FA ratios decreased gradually in the well,moderate,and poor recovery subgroups(P0.05).Conclusion DTI ratios might eliminate the influence of age in evaluating the clinical symptoms and prognosis of CSM.Therefore DTI ratios,compared with DTI parameters,may better evaluate the clinical symptoms,prognosis of CSM.

The sacral networks and neural pathways used to elicit lumbar motor rhythm in the rodent spinal cord.

Identification of neural networks and pathways involved in activation and modulation of spinal central pattern generators (CPGs) in the absence of the descending control from the brain is important for further understanding of neural control of movement and for developing innovative therapeutic approaches to improve the mobility of spinal cord injury patients. Activation of the hindlimb innervating segments by sacrocaudal (SC) afferent input and by specific application of neurochemicals to the sacral networks is feasible in the isolated spinal cord preparation of the newborn rat. Here we review our recent studies of sacral relay neurons with lumbar projections and evaluate their role in linking the sacral and thoracolumbar (TL) networks during different motor behaviors. Our major findings show that: (1) heterogeneous groups of dorsal, intermediate and ventral sacral-neurons with ventral and lateral ascending funicular projections mediate the activation of the locomotor CPGs through sacral sensory input; and (2) rhythmic excitation of lumbar flexor motoneurons, produced by bath application of alpha-1 adrenoceptor agonists to the sacral segments is mediated exclusively by ventral clusters of sacral-neurons with lumbar projections through the ventral funiculus.

Dendritic orientation and branching distinguish a class of multifunctional turtle spinal interneurons.

Spinal interneurons can integrate diverse propriospinal and supraspinal inputs that trigger or modulate locomotion and other limb movements. These synaptic inputs can occur on distal dendrites and yet must remain effective at the soma. Active dendritic conductances may amplify distal dendritic inputs, but appear to play a minimal role during scratching, at least. Another possibility is that spinal interneurons that integrate inputs on distal dendrites have unusually simple dendritic trees that effectively funnel current to the soma. We previously described a class of spinal interneurons, called transverse interneurons (or T neurons), in adult turtles. T neurons were defined as having dendrites that extend further in the transverse plane than rostrocaudally and a soma that extends further mediolaterally than rostrocaudally. T neurons are multifunctional, as they were activated during both swimming and scratching motor patterns. T neurons had higher peak firing rates and larger membrane potential oscillations during scratching than scratch-activated interneurons with different dendritic morphologies (“non-T” neurons). These characteristics make T neurons good candidates to play an important role in integrating diverse inputs and generating or relaying rhythmic motor patterns. Here, we quantitatively investigated additional dendritic morphological characteristics of T neurons as compared to non-T neurons. We found that T neurons have less total dendritic length, a greater proportion of dendritic length in primary dendrites, and dendrites that are oriented more mediolaterally. Thus, T neuron dendritic trees extend far mediolaterally, yet are unusually simple, which may help channel synaptic current from distal dendrites in the lateral and ventral funiculi to the soma. In combination with T neuron physiological properties, these dendritic properties may help integrate supraspinal and propriospinal inputs and generate and/or modulate rhythmic limb movements.

A comparative study of cervical cord diffusion tensor imaging between multiple sclerosis and neuromyelitis optica patients

Objective To assess the diffusion changes of normal appearing spinal cord (NASC) in MRI examination in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Methods Axial diffusion tensor imaging (DTI) of cervical cord was performed in 10 patients with NMO, 14 patients with MS and 13 sex- and age-matched healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the C 2-5 level of spinal cord. Regions of interest (ROIs) were placed in the anterior, lateral, posterior funiculi of spinal cord, and the central gray matter of spinal cord. Results Compared with healthy controls, the values of FA in anterior, lateral and posterior funiculi of spinal cord were significantly decreased ( P < 0.05, for all) and MD in left lateral funiculus, posterior funiculus and gray matter were significantly increased ( P ≤ 0.05, for all) in NMO group, and the FA values of right lateral and posterior funiculi in MS group were significantly decreased ( P < 0.05, for all). Compared with MS group, FA value in patients with NMO was significantly decreased in lateral funiculus, and MD value in left lateral and right posterior funiculi were significantly increased ( P < 0.05, for all). Conclusions NASC diffusion abnormalities were found both in patients with NMO and MS. The difference of DTI indicators between NMO and MS patients may offer important information in the early diagnosis and differential diagnosis of NMO and MS. doi: 10.3969/j.issn.1672-6731.2014.10.007

Projections from the oral pontine reticular nucleus to the spinal cord of the mouse

The present study investigated projections of the mouse oral pontine reticular nucleus (PnO) to the spinal cord by (a) injecting a retrograde tracer fluoro-gold (FG) to the lumbar cord and (b) an anterograde tracer biotinylated dextran amine (BDA) to PnO. We found that PnO projects to the entire spinal cord with an ipsilateral predominance. PnO fibers mainly travel in the ipsilateral ventral funiculus in the entire cord, terminating in laminae 7–10 with a lower density of fibers and boutons in lower segments. A small number of fibers travel in the contralateral ventral funiculus in the cervical cord with a similar terminating pattern to the ipsilateral counterpart. The present study is the first demonstration of PnO fiber terminals in the mouse spinal cord. This pathway might be responsible for muscle atonia during REM sleep, but needs physiological research to confirm this.