In Vivo Contrast-Enhanced MR Imaging for Direct Infusion Into Rat Peripheral Nerve

2008 ◽  
Author(s):  
Xiaoming Chen ◽  
Garrett W. Astary ◽  
Thomas H. Mareci ◽  
Malisa Sarntinoranont
Keyword(s):  
Spinal Cord ◽  
Invasive Surgery ◽  
Peripheral Nerves ◽  
Large Scale ◽  
Neurological Deficits ◽  
Direct Infusion ◽  
Direction Parallel ◽  
Preferred Direction ◽  
Cord Injury

Direct infusion of therapeutic agents into the spinal cord provides a promising way to treat traumatic injury and intrinsic diseases of the spinal cord, which may cause paralysis and other neurological deficits. Direct infusion into the spinal cord involves complex invasive surgery since the spinal cord is well protected by the vertebral bone. Instead, infusion directly into peripheral nerves is of interest since it provides a remote delivery site to the spinal cord, requiring less invasive surgery and reducing the risk of spinal cord injury during surgery. It may also allow targeting of specific neurons at nerve root entry. Previous studies have shown [1, 2] that transport in peripheral nerves is anisotropic with a preferred direction parallel to the fiber tracts. A large-scale longitudinal spread of molecular agents may be obtained and spread of molecular agents into the spinal cord may be possible.

In Vivo MRI of Macromolecular Transport Into the Rat Spinal Cord via Peripheral Nerve Infusion

2009 ◽  
Author(s):  
Xiaoming Chen ◽  
Garrett W. Astary ◽  
Thomas H. Mareci ◽  
Malisa Sarntinoranont
Keyword(s):  
Spinal Cord ◽  
Peripheral Nerves ◽  
Large Scale ◽  
Convection Enhanced Delivery ◽  
Direction Parallel ◽  
Macromolecular Transport ◽  
Preferred Direction ◽  
Fiber Tracts ◽  
Alternative Delivery

Convection-enhanced delivery (CED), or direct infusion, of therapeutic agents into peripheral nerves is of interest since it may provide an alternative delivery route to the spinal cord (SC). This delivery method requires only minimally invasive surgery, reducing the risk of SC injury during surgery. It may also allow targeting of specific neurons entering the SC. Previous studies have shown that transport in peripheral nerves is anisotropic with a preferred direction parallel to the fiber tracts [1, 2]. A large-scale longitudinal spread of macromolecular agents may be obtained and spread of agents into the SC may be possible (Fig. 1).

scholarly journals Pericytes Make Spinal Cord Breathless after Injury

2017 ◽  
Vol 24 (5) ◽  
pp. 440-447 ◽  
Author(s):  
Viviani M. Almeida ◽  
Ana E. Paiva ◽  
Isadora F. G. Sena ◽  
Akiva Mintz ◽  
Luiz Alexandre V. Magno ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Interventions ◽  
Neurological Deficits ◽  
Detailed Knowledge ◽  
Secondary Damage ◽  
Cord Injury ◽  
Specific Proteins

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

scholarly journals Sodium Tanshinone IIA Sulfonate Promotes Spinal Cord Injury Repair  by Inhibiting BSCB Disruption In Vitro and In Vivo

2020 ◽  
Author(s):  
Dan Luo ◽  
Xing Li ◽  
Jiheng Zhan ◽  
Yonghui Hou ◽  
Jiyao Luan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tanshinone Iia ◽  
Neurological Deficits ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Sodium Tanshinone Iia Sulfonate

Abstract Background:Spinal cord injury (SCI) leads to microvascular damage and the destruction of blood spinal cord barrier (BSCB), which progresses to secondary injuries like apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair the damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. We found that STS restored BSCB integrity and promoted microvessel recovery 7 days after SCI in a mouse model. However, the therapeutic effects of STS on damaged BSCB in the early stage of SCI remained uncertain. Methods: we exposed spinal cord microvascular endothelial cells (SCMECs) to H2O2 and treated them with different doses of STS. The mice received intraperitoneal injection of STS after SCI in vivo model. Spinal cord tissue was taken 1 and 3d post-SCI. HE, Nissl staining, BSCB permeability, and the expression levels of tight junction (TJ) and adherens junction (AJ), MMP2, MMP9, NeuN, and C-caspase-3 were analyzed.Results: In addition to protecting the cells from H2O2-induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI as well, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMPs activation and prevented TJ and AJ the loss of proteins. Conclusions:Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

scholarly journals Cortical layer-specific modulation of neuronal activity after sensory deprivation due to spinal cord injury

2020 ◽  
Author(s):  
Marta Zaforas ◽  
Juliana M Rosa ◽  
Elena Alonso-Calviño ◽  
Elena Fernández-López ◽  
Claudia Miguel-Quesada ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Activity ◽  
Large Scale ◽  
Sensory Deprivation ◽  
Sensory Stimulation ◽  
Gamma Oscillations ◽  
Cortical Layer ◽  
Cord Injury

SummaryCortical areas have the capacity of large-scale reorganization following sensory deprivation. However, it remains unclear whether this is a unique process that homogenously affects the entire deprived region or it is suitable to changes depending on local circuitries across layers. By using in vivo electrophysiology to record neuronal activity simultaneously across cortical depth, we showed that sensory deprivation due to spinal cord injury induces layer-specific changes in both spontaneous and evoked-activity. While supragranular layers specifically increased gamma oscillations and the ability to initiate up-states during spontaneous activity, infragranular layers displayed increased, faster and delayed evoked-responses to sensory stimulation. Therefore, sensory deprivation immediately modifies local circuitries allowing supragranular layers to better integrate spontaneous corticocortical information to maintain column excitability, and infragranular layers to better integrate evoked-sensory inputs to preserve subcortical outputs. These layer-specific changes may guide long-term alterations in excitability and plasticity associated to network rearrangements and the appearance of sensory pathologies associated with spinal cord injury.

scholarly journals A Therapeutic Strategy for Spinal Cord Defect: Human Dental Follicle Cells Combined with Aligned PCL/PLGA Electrospun Material

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Xinghan Li ◽  
Chao Yang ◽  
Lei Li ◽  
Jie Xiong ◽  
Li Xie ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Large Scale ◽  
Statistical Significance ◽  
Nerve Fibers ◽  
Neural Regeneration ◽  
Follicle Cells ◽  
Dental Follicle ◽  
Dental Follicle Cells ◽  
Cord Injury

Stem cell implantation has been utilized for the repair of spinal cord injury; however, it shows unsatisfactory performance in repairing large scale lesion of an organ. We hypothesized that dental follicle cells (DFCs), which possess multipotential capability, could reconstruct spinal cord defect (SCD) in combination with biomaterials. In the present study, mesenchymal and neurogenic lineage characteristics of human DFCs (hDFCs) were identified. Aligned electrospun PCL/PLGA material (AEM) was fabricated and it would not lead to cytotoxic reaction; furthermore, hDFCs could stretch along the oriented fibers and proliferate efficiently on AEM. Subsequently, hDFCs seeded AEM was transplanted to restore the defect in rat spinal cord. Functional observation was performed but results showed no statistical significance. The following histologic analyses proved that AEM allowed nerve fibers to pass through, and implanted hDFCs could express oligodendrogenic lineage maker Olig2in vivowhich was able to contribute to remyelination. Therefore, we concluded that hDFCs can be a candidate resource in neural regeneration. Aligned electrospun fibers can support spinal cord structure and induce cell/tissue polarity. This strategy can be considered as alternative proposals for the SCD regeneration studies.

Rehabilitation of the canine patient following spinal cord injury: a practical guide

2021 ◽  
Vol 26 (1) ◽  
pp. 1-6
Author(s):  
Cheryl Corral
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Neurological Deficits ◽  
Practical Guide ◽  
Cord Injury ◽  
Physical Therapies

This article forms part of a series exploring the rehabilitation of the canine shoulder, elbow, back, hip and stifle following injury or disease. Discussed here are different rehabilitation techniques used to address neurological deficits, pain and weakness following spinal injury, including physical therapies, electrotherapies and acupuncture.

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 A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

scholarly journals Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

2020 ◽  
Vol 9 (4) ◽  
pp. 1221 ◽  
Author(s):  
Jacek M. Kwiecien ◽  
Liqiang Zhang ◽  
Jordan R. Yaron ◽  
Lauren N. Schutz ◽  
Christian J. Kwiecien-Delaney ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Low Dose ◽  
Dorsal Column ◽  
Neurological Deficits ◽  
Sustained Delivery ◽  
Post Surgery ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

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