scholarly journals Electrical activity recorded from the spinal cord in freely moving rats using a subdural bioelectronic implant

2021 ◽  
Author(s):  
Bruce C Harland ◽  
Zaid Aqrawe ◽  
Maria Vomero ◽  
Christian Boehler ◽  
Brad Raos ◽  
...  

Bioelectronic devices have found use at the interface with neural tissue to investigate and treat nervous system disorders. Here, we present the development and characterization of a thin flexible bioelectronic implant inserted over the thoracic spinal cord in rats directly in contact with the spinal cord. There was no negative impact on hind-limb functionality nor any change in the volume or shape of the spinal cord. The bioelectronic implant was maintained in rats for a period of 3 months. We present the first subdural recordings of spinal cord activity in freely moving animals. Recordings contained multiple distinct voltage waveform shapes that were typically between 1 to 6 mV and lasted between 0.1 and 1 seconds. In the future, this implant will facilitate the identification of biomarkers in spinal cord injury and recovery, while enabling the delivery of localized treatments.

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1582 ◽  
Author(s):  
Takehiro Sugaya ◽  
Haruo Kanno ◽  
Michiharu Matsuda ◽  
Kyoichi Handa ◽  
Satoshi Tateda ◽  
...  

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.


Spinal Cord ◽  
2010 ◽  
Vol 49 (3) ◽  
pp. 463-471 ◽  
Author(s):  
J Zariffa ◽  
J L K Kramer ◽  
J W Fawcett ◽  
D P Lammertse ◽  
A R Blight ◽  
...  

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Adam Doelman ◽  
Seth Tigchelaar ◽  
Brian McConeghy ◽  
Sunita Sinha ◽  
Martin S. Keung ◽  
...  

Author(s):  
Fedorova Jana ◽  
Kellerova Erika ◽  
Bimbova Katarina ◽  
Pavel Jaroslav

AbstractSpontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.


Author(s):  
Hao Zhang ◽  
Alexander Younsi ◽  
Guoli Zheng ◽  
Mohamed Tail ◽  
Anna-Kathrin Harms ◽  
...  

Abstract Purpose The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats. Methods Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant). Results The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well. Conclusion Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.


BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fangfang Qu ◽  
Zhenzhen Qu ◽  
Yingqian Lv ◽  
Bo Song ◽  
Bailin Wu

Abstract Background Transverse myelitis (TM) is due to inflammatory spinal cord injury with bilateral neurologic involvement, which is sensory, motor, or autonomic in nature. It may be associated with autoimmune disease, vaccination, intoxication and infections. The most common infection cause of TM is Coxsackie virus and Mycoplasma pneumoniae. The cryptococcosis is rare. We present the case of disseminated cryptococcosis revealed by transverse myelitis in an immunocompetent 55-year-old male patient. The literature review is also stated. Case presentation The 55-year-old man suffered from gradual numbness, weakness in both lower limbs and finally paralyzed in the bed. The thoracic spine Computed tomography (CT) was normal, but multiple nodules in the lung were accidentally discovered. Thoracic Magnetic Resonance Imaging (MRI) showed diffused thoracic spinal cord thickening and extensively intramedullary T2 hyper intensity areas. Gadolinium contrast enhanced T1WI showed an intramedullary circle-enhanced nodule at 9th thoracic level. Diagnosis was made by histological examination of the bilateral lung biopsy. The patient was treated successfully with systemic amphotericin B liposome and fluconazole and intrathecal dexamethasone and amphotericin B liposome. Conclusions This is a patient with disseminated cryptococcosis involving the lung, spinal cord and adrenal glands, which is rare in the absence of immunodeficiency.


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