Protective effects of Batroxobin on spinal cord injury in rats

Fan, Hong; Liu, Xia; Tang, Hai‐Bin; Xiao, Peng; Wang, Yazhou; Ju, Gong

doi:10.1007/s12264-013-1354-7

Cited by 27 publications

(18 citation statements)

References 20 publications

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“…A modified spinal contusion model which was more experimentally consistent was adopted [ 14 , 15 ]. Spinal cavity enlarged gradually and reached plateau by 2 weeks post-injury, with reactive astrocytes surrounded at all time points assessed (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For improving the consistency of the experimental data, W. Tazlaff developed a manual graded forceps lateral crush SCI model [ 48 ]. Because it is difficult for manual performance to ensure vertical orientation of the forceps and equal degree of compression of the two sides of the cord, we designed a mechanical version by mounting a pair of forceps on a stereotaxic device, and thereby its two blades could be closed simultaneously from both sides [ 14 ]. Briefly, a 15–30 mm dorsal midline incision was made by bilateral laminectomy.…”

Section: Methodsmentioning

confidence: 99%

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Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury

Fan

Zhang

Shan

et al. 2016

Mol Neurodegeneration

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190

143

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BackgroundA unique feature of the pathological change after spinal cord injury (SCI) is the progressive enlargement of lesion area, which usually results in cavity formation and is accompanied by reactive astrogliosis and chronic inflammation. Reactive astrocytes line the spinal cavity, walling off the lesion core from the normal spinal tissue, and are thought to play multiple important roles in SCI. The contribution of cell death, particularly the apoptosis of neurons and oligodendrocytes during the process of cavitation has been extensively studied. However, how reactive astrocytes are eliminated following SCI remains largely unclear.ResultsBy immunohistochemistry, in vivo propidium iodide (PI)-labeling and electron microscopic examination, here we reported that in mice, reactive astrocytes died by receptor-interacting protein 3 and mixed lineage kinase domain-like protein (RIP3/MLKL) mediated necroptosis, rather than apoptosis or autophagy. Inhibiting receptor-interacting protein 1 (RIP1) or depleting RIP3 not only significantly attenuated astrocyte death but also rescued the neurotrophic function of astrocytes. The astrocytic expression of necroptotic markers followed the polarization of M1 microglia/macrophages after SCI. Depleting M1 microglia/macrophages or transplantation of M1 macrophages could significantly reduce or increase the necroptosis of astrocytes. Further, the inflammatory responsive genes Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) are induced in necroptotic astrocytes. In vitro antagonizing MyD88 in astrocytes could significantly alleviate the M1 microglia/macrophages-induced cell death. Finally, our data showed that in human, necroptotic markers and TLR4/MyD88 were co-expressed in astrocytes of injured, but not normal spinal cord.ConclusionTaken together, these results reveal that after SCI, reactive astrocytes undergo M1 microglia/macrophages-induced necroptosis, partially through TLR/MyD88 signaling, and suggest that inhibiting astrocytic necroptosis may be beneficial for preventing secondary SCI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0081-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury

Fan

Zhang

Shan

et al. 2016

Mol Neurodegeneration

Self Cite

190

143

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“…Then the spinal cord was clipped for 20 s using a modified micro-ophthalmic forcep (53327T, 66 Vision-Tech), which was modified with an attached cushion to maintain a distance of 0.2 mm between the blades. This procedure led to a moderate SCI as shown by previous research [22,23]. Mouse subjected to surgery was administered subcutaneously 1 ml of saline to replace blood volume lost during surgery and then kept on a 37°C heating pad until it regained consciousness.…”

Section: Methodsmentioning

confidence: 92%

G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

et al. 2016

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Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10–12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G-1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal-regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI.

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“…Medical University (Xi'an) [14] contributes an original research article on the role of Batroxobin in protecting neurons, which may have therapeutic potential. Qiang Liu of the First Clinical Medical College of Shanxi Medical University (Taiyuan) [15] reports that valproate reduces autophagy and promotes neuroprotection.…”

Section: Injury Can Cause Neuronal Loss So Keeping Neurons Alive Is mentioning

confidence: 99%

An update on spinal cord injury research

Zou

2013

Neurosci. Bull.

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Spinal cord injury (SCI) is an ever-increasing challenge.Severe injury can cause long-term loss of sensory and motor functions, as well as other chronic conditions, such as neuropathic pain and autonomic dysreflexia. So far, most research has been focused on acute injury. However, due to the lack of treatment, more and more individuals with this condition enter a chronic state, to which very little research effort has been dedicated. SCI is a complex condition. It involves damage to axons, death of neurons, neuroinflammation, glial scar formation, loss of myelin, and lack of remyelination. It is clear that effective treatment will require combinatorial approaches. The 12 invited articles for this special issue on SCI provide an update on many of these areas of SCI research. Here, I highlight the articles and reviews by theme.Severe SCI involves severing of axons, breaking ascending and descending connections. Inhibitory molecules in the environment of the adult central nervous system, such as the myelin-associated inhibitors and proteoglycans in glial scars, were thought to be the major cause of the lack of regeneration for many years [1] .However, efforts to regenerate axons across a lesion site in the mammalian spinal cord by overcoming this inhibition have not been successful. In some cases, axon regeneration into cell grafts can be achieved, as in studies using preconditioning lesion paradigms of sensory axons [2] .But few axons project beyond the lesion and reach longrange targets. In recent years, more attention has been shifted to enhancing the intrinsic growth capacity of adult central nervous system axons. Deletion of pTEN (phosphatase and tensin homolog) induces unprecedented regeneration across the fully-transacted spinal cord [3] .Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] . Molecular mechanisms that promote or inhibit axon growth have been studied, using various injury paradigms, in different neuronal types and species. Some species have poor central regeneration, whereas others have the capacity to regenerate. Axons in the peripheral nervous system of mammals also show extensive regeneration. The review by Martin Oudega of the University of Pittsburgh [7] provides a comprehensive discussion comparing the molecular mechanisms found in mammals and zebrafish.These comparisons allow for a better understanding of the underlying principles. Remarkably, regeneration in the zebrafish central nervous system is also incomplete. Some axon tracts can regenerate but others cannot. This makes zebrafish an interesting model system for SCI research along with the ...

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Protective effects of Batroxobin on spinal cord injury in rats

Cited by 27 publications

References 20 publications

Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury

Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury

G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

An update on spinal cord injury research

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