Oligodendrocyte-protection and remyelination post-spinal cord injuries: A review

被引:101
作者
Mekhail, Mina [1 ]
Almazan, Guillermina [2 ]
Tabrizian, Maryam [1 ,3 ]
机构
[1] McGill Univ, Dept Biomed Engn, Montreal, PQ H3A 2B4, Canada
[2] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3A 2B4, Canada
[3] McGill Univ, Fac Dent, Montreal, PQ H3A 2B4, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Spinal cord injuries; Remyelination; Oligodendrocyte; Biomaterials; Molecular therapies; Drug delivery systems; LEUKEMIA INHIBITORY FACTOR; CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE METHYLPREDNISOLONE; SCHWANN-CELL TRANSPLANTATION; OLFACTORY ENSHEATHING CELLS; GLIAL PROGENITOR CELLS; CILIARY NEUROTROPHIC FACTOR; RANDOMIZED CONTROLLED-TRIAL; ADULT-RAT; FUNCTIONAL RECOVERY;
D O I
10.1016/j.pneurobio.2012.01.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the past four decades, the main focus of investigators in the field of spinal cord regeneration has been to devise therapeutic measures that enhance neural regeneration. More recently, emphasis has been placed on enhancing remyelination and providing oligodendrocyte-protection after a spinal cord injury (SCI). Demyelination post-SCI is part of the cascading secondary injury that takes place immediately after the primary insult; therefore, therapeutic measures are needed to reduce oligodendrocyte death and/or enhance remyelination during the acute stage, preserving neurological functions that would be lost otherwise. In this review a thorough investigation of the oligodendrocyte-protective and remyelinative molecular therapies available to date is provided. The advent of new biomaterials shown to promote remyelination post-SCI is discussed mainly in the context of a combinatorial approach where the biomaterial also provides drug delivery capabilities. The aim of these molecular and biomaterial-based therapies is twofold: (1) oligodendrocyte-protective therapy, which involves protecting already existing oligodendrocytes from undergoing apoptosis/necrosis; and (2) inductive remyelination, which involves harnessing the remyelinative capabilities of endogenous oligodendrocyte precursor cells (OPCs) at the lesion site by providing a suitable environment for their migration, survival, proliferation and differentiation. From the evidence reported in the literature, we conclude that the use of a combinatorial approach including biomaterials and molecular therapies would provide advantages such as: (1) sustained release of the therapeutic molecule, (2) local delivery at the lesion site, and (3) an environment at the site of injury that promotes OPC migration, differentiation and remyelination. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:322 / 339
页数:18
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