scholarly journals Expression of FLRT2 in Postnatal Central Nervous System Development and After Spinal Cord Injury

2021 ◽  
Vol 14 ◽  
Author(s):  
Juntan Li ◽  
Yo Shinoda ◽  
Shuhei Ogawa ◽  
Shunsuke Ikegaya ◽  
Shuo Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Cell Adhesion ◽  
Nervous System Development ◽  
Cns Development ◽  
Thoracic Spinal Cord ◽  
Cord Injury

Fibronectin and leucine-rich transmembrane (FLRT) proteins are necessary for various developmental processes and in pathological conditions. FLRT2 acts as a homophilic cell adhesion molecule, a heterophilic repulsive ligand of Unc5/Netrin receptors, and a synaptogenic molecule; the last feature is mediated by binding to latrophilins. Although the function of FLRT2 in regulating cortical migration at the late gestation stage has been analyzed, little is known about the expression pattern of FLRT2 during postnatal central nervous system (CNS) development. In this study, we used Flrt2-LacZ knock-in (KI) mice to analyze FLRT2 expression during CNS development. At the early postnatal stage, FLRT2 expression was largely restricted to several regions of the striatum and deep layers of the cerebral cortex. In adulthood, FLRT2 expression was more prominent in the cerebral cortex, hippocampus, piriform cortex (PIR), nucleus of the lateral olfactory tract (NLOT), and ventral medial nucleus (VM) of the thalamus, but lower in the striatum. Notably, in the hippocampus, FLRT2 expression was confined to the CA1 region and partly localized on pre- and postsynapses whereas only few expression was observed in CA3 and dentate gyrus (DG). Finally, we observed temporally limited FLRT2 upregulation in reactive astrocytes around lesion sites 7 days after thoracic spinal cord injury. These dynamic changes in FLRT2 expression may enable multiple FLRT2 functions, including cell adhesion, repulsion, and synapse formation in different regions during CNS development and after spinal cord injury.

scholarly journals Beyond the lesion site: minocycline augments inflammation and anxiety-like behavior following SCI in rats through action on the gut microbiota

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Emma K. A. Schmidt ◽  
Pamela J. F. Raposo ◽  
Abel Torres-Espin ◽  
Keith K. Fenrich ◽  
Karim Fouad
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Gut Microbiota ◽  
Microglial Activation ◽  
Motor Recovery ◽  
Long Term Effects ◽  
Cord Injury ◽  
Anti Inflammatory

Abstract Background Minocycline is a clinically available synthetic tetracycline derivative with anti-inflammatory and antibiotic properties. The majority of studies show that minocycline can reduce tissue damage and improve functional recovery following central nervous system injuries, mainly attributed to the drug’s direct anti-inflammatory, anti-oxidative, and neuroprotective properties. Surprisingly the consequences of minocycline’s antibiotic (i.e., antibacterial) effects on the gut microbiota and systemic immune response after spinal cord injury have largely been ignored despite their links to changes in mental health and immune suppression. Methods Here, we sought to determine minocycline’s effect on spinal cord injury-induced changes in the microbiota-immune axis using a cervical contusion injury in female Lewis rats. We investigated a group that received minocycline following spinal cord injury (immediately after injury for 7 days), an untreated spinal cord injury group, an untreated uninjured group, and an uninjured group that received minocycline. Plasma levels of cytokines/chemokines and fecal microbiota composition (using 16s rRNA sequencing) were monitored for 4 weeks following spinal cord injury as measures of the microbiota-immune axis. Additionally, motor recovery and anxiety-like behavior were assessed throughout the study, and microglial activation was analyzed immediately rostral to, caudal to, and at the lesion epicenter. Results We found that minocycline had a profound acute effect on the microbiota diversity and composition, which was paralleled by the subsequent normalization of spinal cord injury-induced suppression of cytokines/chemokines. Importantly, gut dysbiosis following spinal cord injury has been linked to the development of anxiety-like behavior, which was also decreased by minocycline. Furthermore, although minocycline attenuated spinal cord injury-induced microglial activation, it did not affect the lesion size or promote measurable motor recovery. Conclusion We show that minocycline’s microbiota effects precede its long-term effects on systemic cytokines and chemokines following spinal cord injury. These results provide an exciting new target of minocycline as a therapeutic for central nervous system diseases and injuries.

scholarly journals Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury

RSC Advances ◽  
2020 ◽  
Vol 10 (32) ◽  
pp. 18677-18686
Author(s):  
Jia Liu ◽  
Kai Li ◽  
Ke Huang ◽  
Chengliang Yang ◽  
Zhipeng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Traumatic Injury ◽  
High Rate ◽  
Plga Microspheres ◽  
Cord Injury ◽  
The Central Nervous System

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.

Central Nervous System Reorganization and Pain After Spinal Cord Injury: Possible Targets for Physical Therapy—A Systematic Review of Neuroimaging Studies

2020 ◽  
Vol 100 (6) ◽  
pp. 946-962
Author(s):  
Thomas Osinski ◽  
Sessi Acapo ◽  
Djamel Bensmail ◽  
Didier Bouhassira ◽  
Valéria Martinez
Keyword(s):  
Systematic Review ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Physical Therapist ◽  
Anterior Cingulate ◽  
Current Evidence ◽  
Functional Changes ◽  
Cord Injury

Abstract Background Pain is one of the main symptoms associated with spinal cord injury (SCI) and can be associated with changes to the central nervous system (CNS). Purpose This article provides an overview of the evidence relating to CNS changes (structural and functional) associated with pain in SCIs. Data Sources A systematic review was performed, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on PubMed, Embase, and Web of Science in March 2018. Study Selection Studies were selected if they concerned changes in the CNS of patients with SCI, regardless of the type of imagery. Data Extraction Data were extracted by 2 blinded reviewers. Data Synthesis There is moderate evidence for impaired electroencephalographic function and metabolic abnormalities in the anterior cingulate in patients experiencing pain. There is preliminary evidence that patients with pain have morphological and functional changes to the somatosensory cortex and alterations to thalamic metabolism. There are conflicting data regarding the relationships between lesion characteristics and pain. In contrast, patients without pain can display protective neuroplasticity. Limitations and Conclusion Further studies are required to elucidate fully the relationships between pain and neuroplasticity in patients with SCIs. However, current evidence might support the use of physical therapist treatments targeting CNS plasticity in patients with SCI pain.

Peripheral nerve grafts promoting central nervous system regeneration after spinal cord injury in the primate

2002 ◽  
Vol 96 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Allan D. O. Levi ◽  
Hector Dancausse ◽  
Xiuming Li ◽  
Suzanne Duncan ◽  
Laura Horkey ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Peripheral Nerve ◽  
Content Type ◽  
Nerve Grafts ◽  
Cord Injury ◽  
Peripheral Nerve Grafts ◽  
Fine Print

Object. Partial restoration of hindlimb function in adult rats following spinal cord injury (SCI) has been demonstrated using a variety of transplantation techniques. The purpose of the present study was twofold: 1) to determine whether strategies designed to promote regeneration in the rat can yield similar results in the primate; and 2) to establish whether central nervous system (CNS) regeneration will influence voluntary grasping and locomotor function in the nonhuman primate. Methods. Ten cynomologus monkeys underwent T-11 laminectomy and resection of a 1-cm length of hemispinal cord. Five monkeys received six intercostal nerve autografts and fibrin glue containing acidic fibroblast growth factor (2.1 µg/ml) whereas controls underwent the identical laminectomy procedure but did not receive the nerve grafts. At 4 months postgrafting, the spinal cord—graft site was sectioned and immunostained for peripheral myelin proteins, biotinylated dextran amine, and tyrosine hydroxylase, whereas the midpoint of the graft was analyzed histologically for the total number of myelinated axons within and around the grafts. The animals underwent pre- and postoperative testing for changes in voluntary hindlimb grasping and gait. Conclusions. 1) A reproducible model of SCI in the primate was developed. 2) Spontaneous recovery of the ipsilateral hindlimb function occurred in both graft- and nongraft—treated monkeys over time without evidence of recovering the ability for voluntary tasks. 3) Regeneration of the CNS from proximal spinal axons into the peripheral nerve grafts was observed; however, the grafts did not promote regeneration beyond the lesion site. 4) The grafts significantly enhanced (p < 0.0001) the regeneration of myelinated axons into the region of the hemisected spinal cord compared with the nongrafted animals.

Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system

Spinal Cord ◽  
2020 ◽  
Vol 58 (12) ◽  
pp. 1235-1248
Author(s):  
M. J. Mulcahey ◽  
Linda A. T. Jones ◽  
Frank Rockhold ◽  
Rϋediger Rupp ◽  
John L. K. Kramer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Nervous System ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Adaptive Trial

Intrathecal Baclofen for Severe Spasticity Secondary to Spinal Cord Injury

1993 ◽  
Vol 27 (6) ◽  
pp. 767-774 ◽  
Author(s):  
Kelly S. Lewis ◽  
Wade M. Mueller
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Adverse Effects ◽  
Intrathecal Baclofen ◽  
Clinical Effects ◽  
Spinal Cord Trauma ◽  
Open Label ◽  
Cord Injury

OBJECTIVE: To evaluate the use of intrathecal baclofen for the treatment of muscle spasticity in patients with spinal cord injury. DATA SOURCES: A MEDLINE search was used to identify relevant and pertinent literature. Information was obtained from open-label clinical trials, abstracts, conference proceedings, and review articles. Index terms in the search included baclofen, spasticity, intrathecal drug infusion, spinal cord disease, and neurosurgery. DATA EXTRACTION: Studies were selected for review if they evaluated intrathecal baclofen in patients with spinal cord injury. Emphasis was placed on human studies published in the English language. Trials were reviewed by dosage regimen, therapeutic response, adverse effects, and complications. DATA SYNTHESIS: Thus far, intrathecal baclofen administration shows promise in the treatment of spasticity resulting from spinal cord trauma. Few complications and adverse effects have been reported. CONCLUSIONS: Muscle spasms and spasticity constitute a significant problem in spinal cord injuries, interfering with rehabilitation and leading to inconveniences and complications in these patients. Oral baclofen is the drug of choice for spasticity due to spinal cord trauma. It often is ineffective, however, because of the large dosages required to cross the blood-brain barrier and the subsequent appearance of central nervous system adverse effects. These adverse effects are not tolerated by many patients. Intrathecally administered baclofen has been approved by the Food and Drug Administration (FDA) for the treatment of spasticity in patients with spinal cord injury who are refractory to or cannot tolerate oral baclofen. It is intended for use only in implantable pumps approved by the FDA for the administration of baclofen into the intrathecal space. Intrathecal administration achieves high concentrations in the spinal cord with small dosages, thus reducing the incidence of central nervous system adverse effects. To date, approximately 350 patients with spinal cord injury have been treated with intrathecal baclofen. Reductions in spasticity have been demonstrated in both open-label and placebo-controlled trials. Patients also often make substantial gains in activities of daily living. Few adverse effects and complications have been reported. However, tolerance to the clinical effects of intrathecal baclofen has been reported. Further studies are needed to determine specific patient populations that may benefit most from intrathecal baclofen administration. Individual dosage ranges and follow-up care also need to be defined more completely. In addition, the question of whether tolerance detracts from long-term clinical benefits with intrathecal baclofen needs to be addressed.

scholarly journals Identification of clinical and radiographic predictors of central nervous system injury in genetic skeletal disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antônio L Cunha ◽  
Ana P S Champs ◽  
Carla M. Mello ◽  
Mônica M. M. Navarro ◽  
Frederico J. C. Godinho ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Low Back Pain ◽  
Back Pain ◽  
Low Back ◽  
Cns Injury ◽  
Cord Injury ◽  
Skeletal Disorders

AbstractSome studies report neurological lesions in patients with genetic skeletal disorders (GSDs). However, none of them describe the frequency of neurological lesions in a large sample of patients or investigate the associations between clinical and/or radiological central nervous system (CNS) injury and clinical, anthropometric and imaging parameters. The project was approved by the institution’s ethics committee (CAAE 49433215.5.0000.0022). In this cross-sectional observational analysis study, 272 patients aged four or more years with clinically and radiologically confirmed GSDs were prospectively included. Genetic testing confirmed the diagnosis in the FGFR3 chondrodysplasias group. All patients underwent blinded and independent clinical, anthropometric and neuroaxis imaging evaluations. Information on the presence of headache, neuropsychomotor development (NPMD), low back pain, joint deformity, ligament laxity and lower limb discrepancy was collected. Imaging abnormalities of the axial skeleton and CNS were investigated by whole spine digital radiography, craniocervical junction CT and brain and spine MRI. The diagnostic criteria for CNS injury were abnormal clinical and/or radiographic examination of the CNS. Brain injury included malacia, encephalopathies and malformation. Spinal cord injury included malacia, hydrosyringomyelia and spinal cord injury without radiographic abnormalities. CNS injury was diagnosed in more than 25% of GSD patients. Spinal cord injury was found in 21.7% of patients, and brain injury was found in 5.9%. The presence of low back pain, os odontoideum and abnormal NPMD remained independently associated with CNS injury in the multivariable analysis. Early identification of these abnormalities may have some role in preventing compressive CNS injury, which is a priority in GSD patients.

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