Measurement of Intraspinal Pressure After Spinal Cord Injury: Technical Note from the Injured Spinal Cord Pressure Evaluation Study

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

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Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury

Molecular Brain ◽

10.1186/1756-6606-6-3 ◽

2013 ◽

Vol 6 (1) ◽

pp. 3 ◽

Cited By ~ 91

Author(s):

Soraya Nishimura ◽

Akimasa Yasuda ◽

Hiroki Iwai ◽

Morito Takano ◽

Yoshiomi Kobayashi ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Neural Stem Cell ◽

Therapeutic Potential ◽

Time Dependent ◽

Injured Spinal Cord ◽

Cord Injury

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Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury

Journal of Neurosurgery Spine ◽

10.3171/spi.2001.94.2.0257 ◽

2001 ◽

Vol 94 (2) ◽

pp. 257-264 ◽

Cited By ~ 8

Author(s):

Mercedes Zurita ◽

Jesús Vaquero ◽

Isabel Zurita

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Gray Matter ◽

Spinal Cord Tissue ◽

Injured Spinal Cord ◽

Content Type ◽

Cord Injury ◽

Positive Immunostaining ◽

Fine Print

Object. A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI. Methods. The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord. Conclusions. These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.

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The Injured Spinal Cord: Imaging, Histopathologic, Clinical Correlates, and Basic Science Approaches to Enhancing Neural Function After Spinal Cord Injury

Spine ◽

10.1097/00007632-199609150-00002 ◽

1996 ◽

Vol 21 (18) ◽

pp. 2064-2066 ◽

Cited By ~ 50

Author(s):

Robert M. Quencer ◽

Richard P. Bunge

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Basic Science ◽

Neural Function ◽

Injured Spinal Cord ◽

Clinical Correlates ◽

Cord Injury ◽

Spinal Cord Imaging

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In vivo conversion of rat astrocytes into neuronal cells through neural stem cells in injured spinal cord with a single zinc-finger transcription factor

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1448-x ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Masoumeh Zarei-Kheirabadi ◽

Mahdi Hesaraki ◽

Sahar Kiani ◽

Hossein Baharvand

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

Rating Scale ◽

Injured Spinal Cord ◽

Functional Impairments ◽

Cord Injury ◽

Rat Astrocytes

Abstract Background Spinal cord injury (SCI) results in glial scar formation and irreversible neuronal loss, which finally leads to functional impairments and long-term disability. Our previous studies have demonstrated that the ectopic expression of Zfp521 reprograms fibroblasts and astrocytes into induced neural stem cells (iNSCs). However, it remains unclear whether treatment with Zfp521 also affects endogenous astrocytes, thus promoting further functional recovery following SCI. Methods Rat astrocytes were transdifferentiated into neural stem cells in vitro by ZFP521 or Sox2. Then, ZFP521 was applied to the spinal cord injury site of a rat. Transduction, real-time PCR, immunohistofluorescence, and function assessments were performed at 6 weeks post-transduction to evaluate improvement and in vivo lineage reprogramming of astrocytes. Results Here, we show that Zfp521 is more efficient in reprogramming cultured astrocytes compared with Sox2. In the injured spinal cord of an adult rat, resident astrocytes can be reprogrammed into neurons through a progenitor stage by Zfp521. Importantly, this treatment improves the functional abilities of the rats as evaluated by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and further by calculation of its subscores. There was enhanced locomotor activity in the hind limbs, step length, toe spread, foot length, and paw area. In addition, motor evoked potential recordings demonstrated the functional integrity of the spinal cord. Conclusions These results have indicated that the generation of iNSCs or neurons from endogenous astrocytes by in situ reprogramming might be a potential strategy for SCI repair. Graphical abstract

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