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Adv Mater. 2018 Apr;30(14):e1706032. doi: 10.1002/adma.201706032. Epub 2018 Feb 14.

Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity.

Author information

1
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
2
Helsinki Institute of Life Science, HiLIFE, University of Helsinki, FI-0014, Helsinki, Finland.
3
John A. Paulson School of Applied Science and Engineering, Harvard University, Cambridge, MA, 02138, USA.
4
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
5
Department of Orthopaedics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China.
6
Institute of Sport Medicine, The Affiliated Hospital of Nanjing, University of TCM, Nanjing, 210004, China.
7
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Abstract

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases.

KEYWORDS:

acetalated dextran; alleviated excitotoxicity; calcium ion scavenging; glutamate adsorption; spinal cord injury

PMID:
29441625
DOI:
10.1002/adma.201706032
[Indexed for MEDLINE]

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