Dataset Information

Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat model of lumbar spinal cord transection.

ABSTRACT: A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when prepared as 1wt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1 (L₁) level. In vivo and in vitro experiments (n = 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L₁ level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200 (NF200) antibody and astrocytic scar marker glial fibrillary acidic protein (GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SY5Y cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that TexasPEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.

SUBMITTER: Kim CY

PROVIDER: S-EPMC6108198 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat model of lumbar spinal cord transection.

Kim C-Yoon CY Sikkema William K A WKA Kim Jin J Kim Jeong Ah JA Walter James J Dieter Raymond R Chung Hyung-Min HM Mana Andrea A Tour James M JM Canavero Sergio S

Neural regeneration research 20180801 8

A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when prepared as 1wt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular l ...[more]

PMID: 30106057

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Project description:Spinal cord injury (SCI) often leads to persistent functional deficits due to severe neuron and glial loss, and to limited axonal regeneration after injury. Here we show that the transplantation of human dental stem cells into the completely transected adult rat spinal cord resulted in a significant recovery of hindlimb locomotor functions. These stem cells exhibited three major neuro-regenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, improving the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, by paracrine mechanisms. Third, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide novel therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuro-regenerative activities. Human dental stem cells were isolated from exfoliated deciduous teeth extracted for clinical purposes were collected at Nagoya University School of Medicine, under approved guidelines set by Nagoya University (H-73, 2003). The ethics committee of Nagoya University approved the experimental protocols (permission number 8-2). Mesenchymal stem cells of human Bone marrow line were obtained from Lonza. Total RNAs were isolated and quantified by spectrophotometer. RNA integrity was checked on 1% agarose gels. RT reactions were carried out with Superscript III reverse transcriptase (Invitrogen) using 1 μg of total RNA in a 50 μl total reaction volume. Microarray experiments were carried out using a CodeLink™ Human Whole Genome Bioarray (Applied Microarrays, Inc. Tempe, AZ) at Filgen, Inc. (Nagoya, Japan). The arrays were scanned using a GenePix4000B Array Scanner (Molecular Devices, Sunnyvale, CA), and the data was analyzed by using MicroArray Data Analysis Tool Ver3.2 (Filgen, Inc.).

Project description:Microtubule stabilization through epothilones is a promising preclinical therapy for functional recovery following spinal cord injury that stimulates axon regeneration, reduces growth-inhibitory molecule deposition and promotes functional improvements. Rehabilitation therapy is the only clinically validated approach to promote functional improvements following spinal cord injury. However, whether microtubule stabilization can augment the beneficial effects of rehabilitation therapy or act in concert with it to further promote repair remains unknown. Here, we investigated the pharmacokinetic, histological and functional efficacies of epothilone D, epothilone B and ixabepilone alone or in combination with rehabilitation following a moderate contusive spinal cord injury. Pharmacokinetic analysis revealed that ixabepilone only weakly crossed the blood-brain barrier and was subsequently excluded from further investigations. In contrast, epothilones B and D rapidly distributed to CNS compartments displaying similar profiles after either subcutaneous or intraperitoneal injections. Following injury and subcutaneous administration of epothilone B or D, rats were subjected to 7 weeks of sequential bipedal and quadrupedal training. For all outcome measures, epothilone B was efficacious compared with epothilone D. Specifically, epothilone B decreased fibrotic scaring which was associated with a retention of fibronectin localized to perivascular cells in sections distal to the lesion. This corresponded to a decreased number of cells present within the intralesional space, resulting in less axons within the lesion. Instead, epothilone B increased serotonergic fibre regeneration and vesicular glutamate transporter 1 expression caudal to the lesion, which was not affected by rehabilitation. Multiparametric behavioural analyses consisting of open-field locomotor scoring, horizontal ladder, catwalk gait analysis and hindlimb kinematics revealed that rehabilitation and epothilone B both improved several aspects of locomotion. Specifically, rehabilitation improved open-field locomotor and ladder scores, as well as improving the gait parameters of limb coupling, limb support, stride length and limb speed; epothilone B improved these same gait parameters but also hindlimb kinematic profiles. Functional improvements by epothilone B and rehabilitation acted complementarily on gait parameters leading to an enhanced recovery in the combination group. As a result, principal component analysis of gait showed the greatest improvement in the epothilone B plus rehabilitation group. Thus, these results support the combination of epothilone B with rehabilitation in a clinical setting.

Dataset Information

Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat model of lumbar spinal cord transection.

Publications

Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat model of lumbar spinal cord transection.

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