Early graft of neural precursors in spinal cord compression reduces glial cyst and improves function

被引:17
作者
Boido, Marina [1 ]
Garbossa, Diego [2 ]
Vercelli, Alessandro [1 ]
机构
[1] Cavalieri Ottolenghi Fdn, Inst Neurosci, Neurosci Inst Turin, I-10043 Turin, Italy
[2] Univ Turin, Dept Neurosci, I-10124 Turin, Italy
关键词
spinal cord injury; cell therapy; CNS repair; glial cyst; CEREBRAL-ARTERY OCCLUSION; STEM-CELLS; REACTIVE ASTROCYTES; RESTRICTED PRECURSORS; TRANSPLANTATION; INJURY; MOUSE; RECOVERY; SURVIVAL; NEURONS;
D O I
10.3171/2011.1.SPINE10607
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Object. Spinal cord injury (SCI) often results in irreversible and permanent neurological deficits below the injury site and is considered a pathological state of functional damage to local neurons and axon fibers. There are several experimental treatments to minimize tissue damage, and recently cell transplantation has emerged as a promising approach in spinal cord repair. The authors undertook this study to evaluate grafting of neural tube precursors as a possible therapeutic strategy in a model of spinal cord compression in the mouse. Methods. Compression SCI was induced at the T-13 level in adult male mice. Immediately after injury, neural precursor cells (NPs) were transplanted into the SCI lesion cavity in 18 mice; the remaining 19 mice received saline injections into the lesion cavity and were used as controls. Spinal cords were examined 12,19, and 26 days postinjury to investigate the survival of the NPs and their effects on the cellular environment, glial scar and glial cyst formation, astrogliosis, and microglial activation. Results. Grafted NPs survived well and integrated into the host spinal cord tissue. Some NPs had differentiated into cells expressing glial and neuronal markers at all 3 end points. Analysis of glial cyst volume showed a lesion volume reduction of 63.2% in the NP-treated mice compared with volume in the injured but untreated mice. There appeared to be no difference in astroglial and microglial activation between untreated mice and treated ones. Sensory and motor tests demonstrated that transplantation of NPs promoted improvement in injured and treated animals compared with controls. Conclusions. These results support the therapeutic potential of NPs, demonstrating that they can survive for a long time, differentiate, integrate into the injured spinal cord, and promote functional recovery after SCI. (DOI: 10.3171/2011.1.SPINE10607)
引用
收藏
页码:97 / 106
页数:10
相关论文
共 58 条
[11]   The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells [J].
Eljaschewitsch, E ;
Witting, A ;
Mawrin, C ;
Lee, T ;
Schmidt, PM ;
Wolf, S ;
Hoertnagl, H ;
Raine, CS ;
Schneider-Stock, R ;
Nitsch, R ;
Ullrich, O .
NEURON, 2006, 49 (01) :67-79
[12]   Spinal cord compression injury in the mouse: presentation of a model including assessment of motor dysfunction [J].
Farooque, M .
ACTA NEUROPATHOLOGICA, 2000, 100 (01) :13-22
[13]   Reactive astrocytes protect tissue and preserve function after spinal cord injury [J].
Faulkner, JR ;
Herrmann, JE ;
Woo, MJ ;
Tansey, KE ;
Doan, NB ;
Sofroniew, MV .
JOURNAL OF NEUROSCIENCE, 2004, 24 (09) :2143-2155
[14]   The glial scar and central nervous system repair [J].
Fawcett, JW ;
Asher, RA .
BRAIN RESEARCH BULLETIN, 1999, 49 (06) :377-391
[15]   The adult "paraplegic" rat: treatment with cell graftings [J].
Fernandez, Eduardo ;
Mannino, Stefano ;
Tufo, Tommaso ;
Pallini, Roberto ;
Lauretti, Liverana ;
Albanese, Alessio ;
Denaro, Luca .
SURGICAL NEUROLOGY, 2006, 65 (03) :223-237
[16]   NEUROLOGICAL DEFICIT AND EXTENT OF NEURONAL NECROSIS ATTRIBUTABLE TO MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS - STATISTICAL VALIDATION [J].
GARCIA, JH ;
WAGNER, S ;
LIU, KF ;
HU, XJ .
STROKE, 1995, 26 (04) :627-634
[17]   Transplantation of glial-restricted precursor cells into the adult spinal cord: Survival, glial-specific differentiation, and preferential migration in white matter [J].
Han, SSW ;
Liu, Y ;
Tyler-Polsz, C ;
Rao, MS ;
Fischer, I .
GLIA, 2004, 45 (01) :1-16
[18]   Grafted lineage-restricted precursors differentiate exclusively into neurons in the adult spinal cord [J].
Han, SSW ;
Kang, DY ;
Mujtaba, T ;
Rao, MS ;
Fischer, I .
EXPERIMENTAL NEUROLOGY, 2002, 177 (02) :360-375
[19]   Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury? [J].
Harel, Noam Y. ;
Strittmatter, Stephen M. .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (08) :603-616
[20]   Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery [J].
Hooshmand, Mitra J. ;
Sontag, Christopher J. ;
Uchida, Nobuko ;
Tamaki, Stan ;
Anderson, Aileen J. ;
Cummings, Brian J. .
PLOS ONE, 2009, 4 (06)