scholarly journals Mechanical mapping of spinal cord development and repair in living zebrafish larvae using Brillouin microscopy

2017 ◽  
Author(s):  
Raimund Schlüßler ◽  
Stephanie Möllmert ◽  
Shada Abuhattum ◽  
Gheorghe Cojoc ◽  
Paul Müller ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Measurement Techniques ◽  
Biological Tissues ◽  
Tissue Mechanics ◽  
Spinal Cord Tissue ◽  
Tissue Properties ◽  
Zebrafish Larvae ◽  
Cord Injury

AbstractThe mechanical properties of biological tissues are increasingly recognized as important factors in developmental and pathological processes. Most existing mechanical measurement techniques either necessitate destruction of the tissue for access or provide insufficient spatial resolution. Here, we show for the first time a systematic application of confocal Brillouin microscopy to quantitatively map the mechanical properties of spinal cord tissues during biologically relevant processes in a contact-free and non-destructive manner. Living zebrafish larvae were mechanically imaged in all anatomical planes, during development and after spinal cord injury. These experiments revealed that Brillouin microscopy is capable of detecting the mechanical properties of distinct anatomical structures without interfering with the animal’s natural development. The Brillouin shift within the spinal cord increased during development and transiently decreased during the repair processes following spinal cord transection. By taking into account the refractive index distribution, we explicitly determined the apparent longitudinal modulus and viscosity of different larval zebrafish tissues. Importantly, mechanical properties differed between tissues in situ and in excised slices. The presented work constitutes the first step towards an in vivo assessment of spinal cord tissue mechanics during regeneration, provides a methodical basis to identify key determinants of mechanical tissue properties and allows to test their relative importance in combination with biochemical and genetic factors during developmental and regenerative processes.

scholarly journals In Vivo Tissue-Level Thresholds for Spinal Cord Injury

2007 ◽  
Author(s):  
Jason Maikos ◽  
Ragi Elias ◽  
Zhen Qian ◽  
Dimitris Metaxas ◽  
David Shreiber
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Small Animal ◽  
Tissue Level ◽  
Spine Injury ◽  
Spinal Cord Tissue ◽  
Element Analysis ◽  
In Vivo Models ◽  
Cord Injury

Traumatic loading conditions, such as those experienced during car accidents or falls, can lead to spinal cord injury (SCI), resulting in permanent functional damage [1]. A better understanding of the biomechanical causes of SCI and knowledge of the tolerance of spinal cord tissue to mechanical loading is critical in understanding how mechanisms of injury lead to neurologic deficits, as well as designing methods to prevent SCI. Finite element analysis (FEA) has become an important and cost effective tool to investigate the biomechanics of trauma. FEA has been used to study a variety of biomechanical analyses of trauma, including brain injury and spine injury biomechanics, but there have been limited analyses on spinal cord injury (SCI) [2–5]. In fact, despite the prevalence of small animal models in the neuroscience community used to study SCI, there have been no published analyses of in vivo models of SCI.

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 MicroRNA-182 improves spinal cord injury in mice by modulating apoptosis and the inflammatory response via IKKβ/NF-κB

2021 ◽  
Author(s):  
Min Fei ◽  
Zheng Li ◽  
Yuanwu Cao ◽  
Chang Jiang ◽  
Haodong Lin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Cell Damage ◽  
Secondary Injury ◽  
Spinal Cord Tissue ◽  
Iκb Kinase ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase β (IKKβ), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKβ reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p‑) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKβ/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.

scholarly journals MicroRNA-145-Mediated KDM6A Downregulation Enhances Neural Repair after Spinal Cord Injury via the NOTCH2/Abcb1a Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Changzhao Gao ◽  
Fei Yin ◽  
Ran Li ◽  
Qing Ruan ◽  
Chunyang Meng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Pc12 Cells ◽  
Functional Recovery ◽  
Pc12 Cell ◽  
Spinal Cord Tissue ◽  
Neural Repair ◽  
Cord Injury

Spinal cord injury (SCI) causes a significant physical, emotional, social, and economic burden to millions of people. MicroRNAs are known players in the regulatory circuitry of the neural repair in SCI. However, most microRNAs remain uncharacterized. Here, we demonstrate the neuroprotection of microRNA-145 (miR-145) after SCI in vivo and in vitro. In silico analysis predicted the target gene KDM6A of miR-145. The rat SCI model was developed by weight drop, and lipopolysaccharide- (LPS-) induced PC12 cell inflammatory injury model was also established. We manipulated the expression of miR-145 and/or KDM6A both in vivo and in vitro to explain their roles in rat neurological functional recovery as well as PC12 cell activities and inflammation. Furthermore, we delineated the mechanistic involvement of NOTCH2 and Abcb1a in the neuroprotection of miR-145. According to the results, miR-145 was poorly expressed and KDM6A was highly expressed in the spinal cord tissue of the SCI rat model and LPS-induced PC12 cells. Overexpression of miR-145 protects PC12 cells from LPS-induced cell damage and expedites neurological functional recovery of SCI in rats. miR-145 was validated to target and downregulate the demethylase KDM6A expression, thus abrogating the expression of Abcb1a by promoting the methylation of NOTCH2. Additionally, in vivo findings verified that miR-145 expedites neuroprotection after SCI by regulating the KDM6A/NOTCH2/Abcb1a axis. Taken together, miR-145 confers neuroprotective effects and enhances neural repair after SCI through the KDM6A-mediated NOTCH2/Abcb1a axis.

scholarly journals Endogenous Two-Photon Excited Fluorescence Provides Label-Free Visualization of the Inflammatory Response in the Rodent Spinal Cord

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ortrud Uckermann ◽  
Roberta Galli ◽  
Rudolf Beiermeister ◽  
Kerim-Hakan Sitoci-Ficici ◽  
Robert Later ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Inflammatory Responses ◽  
Second Harmonic ◽  
Future Application ◽  
Spinal Cord Tissue ◽  
Label Free ◽  
Two Photon ◽  
Cord Injury

Activation of CNS resident microglia and invasion of external macrophages plays a central role in spinal cord injuries and diseases. Multiphoton microscopy based on intrinsic tissue properties offers the possibility of label-free imaging and has the potential to be applied in vivo. In this work, we analyzed cellular structures displaying endogenous two-photon excited fluorescence (TPEF) in the pathologic spinal cord. It was compared qualitatively and quantitatively to Iba1 and CD68 immunohistochemical staining in two models: rat spinal cord injury and mouse encephalomyelitis. The extent of tissue damage was retrieved by coherent anti-Stokes Raman scattering (CARS) and second harmonic generation imaging. The pattern of CD68-positive cells representing postinjury activated microglia/macrophages was colocalized to the TPEF signal. Iba1-positive microglia were found in areas lacking any TPEF signal. In peripheral areas of inflammation, we found similar numbers of CD68-positive microglia/macrophages and TPEF-positive structures while the number of Iba1-positive cells was significantly higher. Therefore, we conclude that multiphoton imaging of unstained spinal cord tissue enables retrieving the extent of microglia activation by acquisition of endogenous TPEF. Future application of this technique in vivo will enable monitoring inflammatory responses of the nervous system allowing new insights into degenerative and regenerative processes.

Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses

2004 ◽  
Vol 91 (01) ◽  
pp. 162-170 ◽  
Author(s):  
Koji Hirose ◽  
Yuji Taoka ◽  
Mitsuhiro Uchiba ◽  
Kan-yu Nakano ◽  
Junichi Utoh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Spinal Cord Tissue ◽  
Protective Effects ◽  
Tissue Levels ◽  
Cord Injury

SummaryAntithrombin (AT) reveals its antiinflammatory activity by promoting endothelial release of prostacyclin (PGI2) in vivo. Since neuroinflammation is critically involved in the development of ischemia/reperfusion (I/R)-induced spinal cord injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating the inflammatory responses. We examined this possibility using rat model of I/R-induced SCI in the present study. AT significantly reduced the mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. Microinfarctions of the spinal cord seen after reperfusion were markedly reduced by AT. AT significantly enhanced the I/R-induced increases in spinal cord tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2. AT significantly inhibited the I/R-induced increases in spinal cord tissue levels of TNF-α, rat interleukin-8 and myeloperoxidase. In contrast,Trp49-modified AT did not show any protective effects. Pretreatment with indomethacin significantly reversed the protective effects of AT.An inactive derivative of factor Xa, which selectively inhibits thrombin generation, has been shown to fail to reduce SCI.Taken together, these observations strongly suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory effect through promotion of endothelial production of PGI2. These findings also suggested that AT might be a potential neuroprotective agent.

scholarly journals Passive myocardial mechanical properties: meaning, measurement, models

2021 ◽  
Vol 13 (5) ◽  
pp. 587-610
Author(s):  
Ramona Emig ◽  
Callum M. Zgierski-Johnston ◽  
Viviane Timmermann ◽  
Andrew J. Taberner ◽  
Martyn P. Nash ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Myocardial Contraction ◽  
Experimental Models ◽  
Tissue Mechanics ◽  
Tissue Properties ◽  
Measurement Models ◽  
Spatio Temporal ◽  
Mechanical Tissue

AbstractPassive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.

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 Concomitant control of mechanical properties and degradation in resorbable elastomer-like materials using stereochemistry and stoichiometry for soft tissue engineering

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Beth Wandel ◽  
Craig A. Bell ◽  
Jiayi Yu ◽  
Maria C. Arno ◽  
Nathan Z. Dreger ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Drug Delivery ◽  
Soft Tissue ◽  
Tissue Regeneration ◽  
Biological Tissues ◽  
Soft Tissue Regeneration ◽  
Soft Tissue Engineering ◽  
Degradation Properties ◽  
Enhance Cell Adhesion

AbstractComplex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical, and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.

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