scholarly journals Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David O. Dias ◽  
Jannis Kalkitsas ◽  
Yildiz Kelahmetoglu ◽  
Cynthia P. Estrada ◽  
Jemal Tatarishvili ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Stromal Cells ◽  
Type A ◽  
Perivascular Cells ◽  
Fibrotic Tissue ◽  
Cord Injury ◽  
Brain And Spinal Cord

AbstractFibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models that develop fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes. Perivascular cells with a type A pericyte marker profile also exist in the human brain and spinal cord. We uncover type A pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

scholarly journals Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

2020 ◽  
Author(s):  
David O. Dias ◽  
Jannis Kalkitsas ◽  
Yildiz Kelahmetoglu ◽  
Cynthia P. Estrada ◽  
Jemal Tatarishvili ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Stromal Cells ◽  
Primary Source ◽  
Lineage Tracing ◽  
Fibrotic Tissue ◽  
Cord Injury

AbstractFibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models developing fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes.We uncover pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

1982 ◽  
Vol 60 (11) ◽  
pp. 1415-1424 ◽  
Author(s):  
H. B. Demopoulos ◽  
E. S. Flamm ◽  
M. L. Seligman ◽  
D. D. Pietronigro ◽  
J. Tomasula ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Free Radical ◽  
Tissue Injury ◽  
Functional Restoration ◽  
Radical Reactions ◽  
Free Radical Reactions ◽  
Cord Injury

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

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.

SUBPIAL HEMANGIOPERICYTOMA WITH MARKED EXTRAMEDULLARY GROWTH

Neurosurgery ◽  
2007 ◽  
Vol 61 (6) ◽  
pp. E1336-E1337 ◽  
Author(s):  
Daina Kashiwazaki ◽  
Kazutoshi Hida ◽  
Shunsuke Yano ◽  
Toshitaka Seki ◽  
Yoshinobu Iwasaki
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Thoracic Spine ◽  
Vascular Tumors ◽  
First Case ◽  
Intradural Tumor ◽  
The Central Nervous System ◽  
Fibrous Tumor ◽  
Brain And Spinal Cord

Abstract OBJECTIVE Hemangiopericytomas, vascular tumors arising in soft tissue, are relatively rare in the central nervous system; they comprise less than 1% of all hemangiopericytomas. Central nervous system hemangiopericytomas occur primarily in the epidural space of the brain and spinal cord. There are no previous reports of subpial, extramedullary growing central nervous system hemangiopericytomas. CLINICAL PRESENTATION We document the first case of a subpial hemangiopericytoma with extramedullary growth in the thoracic spine. The patient was a 31-year-old man who developed progressively worsening left lower limb numbness that was followed by gait disturbance over the course of 4 months. INTERVENTION Magnetic resonance imaging revealed an intradural tumor at the T4–T6 level of the thoracic spine. Because the patient's symptoms progressed, he underwent resection of the tumor, which had arisen in the spinal cord subpially without attachment to the dura mater. CONCLUSION The pathological diagnosis was hemangiopericytoma. Differential diagnoses include hemangioblastoma, meningioma, schwannoma, and solitary fibrous tumor, the clinical course and prognosis of which are different from hemangiopericytoma. Our experience indicates that hemangiopericytomas can occur as intradural tumors arising from the subpial portion.

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