White matter inhibitors in CNS axon regeneration failure

Xie, Fang; Zheng, Binhai

doi:10.1016/j.expneurol.2007.07.005

Cited by 90 publications

(62 citation statements)

References 98 publications

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“…Due to the non-responsive environment of the injured spinal cord, axon regeneration does not occur (20,22). Besides, the loss of function after SCI might be from both the primary mechanical insult and the subsequent, multifaceted secondary degenerative response.…”

Section: Introductionmentioning

confidence: 99%

Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation

Karaöz¹,

Kabataş²,

Duruksu³

et al. 2011

Turkish Neurosurgery

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AIm:This study aimed to analyze the effect of rat bone marrow-mesenchymal stem cells (rBM-MSCs) delivery on lesion site after spinal cord injury, and to observe the functional recovery after transplantation. mAterIAl and methOds: MSCs were isolated from rat femurs and tibias. The experimental rat population was divided into four groups: only laminectomy (1); laminectomy+trauma (2); laminectomy+trauma+PBS (3); laminectomy+trauma+MSCs (4). Their motility were scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for GFP labeled rBM-MSCs by immunostainings. results:In the early posttraumatic period, the ultrastructures of spinal cord tissue were preserved in Group 4. The majority of cells forming the ependymal region around the central canal were found to be MSCs. The gray-and-white-matter around the ependymal region were composed of Nestin+/GFAP+ cells, with astrocytic-like appearance. The scores showed significant motor recovery in Group 4, especially in hind limb functions. However, no obvious change was observed in other groups. COnClusIOn:The increase Nestin+/GFAP+ cells in the gray-and-white-matter around the ependymal region could indicate the potential to self-renew and plasticity. Thus, transplantation of rBM-MSCs might be an effective strategy to improve functional recovery following spinal cord trauma. In conclusion, molecular factors in cell fate decisions could be manipulated to enhance reparative potential of cell-based therapy. KeywOrds: Bone marrow, Mesenchymal stem cells, Spinal cord injury, Functional recovery, Rats ÖZAmAÇ: Bu çalışmada omurilik hasarı sonrası sıçan kemik iliği-mezenkimal kök hücrelerinin (sKİ-MKH) lezyon yerindeki etkisini analiz etmek ve transplantasyon sonrası işlevsel iyileşmeyi gözlemlemek amaçlandı. yÖntem ve GereÇler: MKH'ler sıçan femur ve tibialarından izole edildi. Deney sıçanları dört gruba ayrıldı: sadece laminektomi (1), laminektomi+ travma (2); laminektomi + travma + PBS (3); laminektomi + travma + MKH'ler (4). Sıçanların hareketleri düzenli olarak skorlandı. Dört hafta sonra sıçanlar sakrifiye edildi, omurilikleri immün boyamayla GFP işaretli sKİ-MKH'lerle incelendi.BulGulAr: Erken posttravmatik dönemde, Grup 4'teki omurilik dokusu ultrastrüktürel olarak korundu. Santral kanalın etrafındaki ependimal bölgeyi oluşturan hücrelerinin çoğu MKH'ler olarak saptandı. Ependimal bölgenin etrafındaki gri ve ak maddeler astrositik görünümlü Nestin+/ GFAP+ hücrelerden oluşmuştu. Grup 4'te özellikle arka bacak fonksiyonlarında motor iyileşme belirgindi. Buna karşın, diğer gruplarda belirgin değişiklik izlenmedi.sOnuÇ: Ependimal bölgenin etrafındaki gri ve ak maddede Nestin+/GFAP+ hücrelerin artışı kendini yenileme ve plastisite potansiyellerini gösterebilir ve sKİ-MKH'lerin transplantasyonu spinal kord travması sonrası fonksiyonel iyileşmede etkili bir strateji olabilir. Sonuç olarak, moleküler faktörler hücre kaderini belirleyen hücre tabanlı tedavinin onarıcı potansiyelini artırmak için uygulanabilir.

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Section: Introductionmentioning

confidence: 99%

Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation

Karaöz¹,

Kabataş²,

Duruksu³

et al. 2011

Turkish Neurosurgery

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“…The Nogo receptor family members Nogo-66 receptor 1 (NgR1) and NgR2 support high-affinity binding of myelin inhibitors and have been implicated in regulating neuronal structure (Xie and Zheng, 2008). NgR1 has been proposed to regulate RhoA activation through association with Lingo-1 and p75 or Taj/TROY (Yiu and He, 2006).…”

Section: Introductionmentioning

confidence: 99%

Synaptic Function for the Nogo-66 Receptor NgR1: Regulation of Dendritic Spine Morphology and Activity-Dependent Synaptic Strength

Lee¹,

Raiker²,

Venkatesh³

et al. 2008

J. Neurosci.

152

210

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In the mature nervous system, changes in synaptic strength correlate with changes in neuronal structure. Members of the Nogo-66 receptor family have been implicated in regulating neuronal morphology. Nogo-66 receptor 1 (NgR1) supports binding of the myelin inhibitors Nogo-A, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), and is important for growth cone collapse in response to acutely presented inhibitors in vitro. After injury to the corticospinal tract, NgR1 limits axon collateral sprouting but is not important for blocking long-distance regenerative growth in vivo. Here, we report on a novel interaction between NgR1 and select members of the fibroblast growth factor (FGF) family. FGF1 and FGF2 bind directly and with high affinity to NgR1 but not to NgR2 or NgR3. In primary cortical neurons, ectopic NgR1 inhibits FGF2-elicited axonal branching. Loss of NgR1 results in altered spine morphologies along apical dendrites of hippocampal CA1 neurons in vivo. Analysis of synaptosomal fractions revealed that NgR1 is enriched synaptically in the hippocampus. Physiological studies at Schaffer collateral-CA1 synapses uncovered a synaptic function for NgR1. Loss of NgR1 leads to FGF2-dependent enhancement of long-term potentiation (LTP) without altering basal synaptic transmission or short-term plasticity. NgR1 and FGF receptor 1 (FGFR1) are colocalized to synapses, and mechanistic studies revealed that FGFR kinase activity is necessary for FGF2-elicited enhancement of hippocampal LTP in NgR1 mutants. In addition, loss of NgR1 attenuates long-term depression of synaptic transmission at Schaffer collateral-CA1 synapses. Together, our findings establish that physiological NgR1 signaling regulates activity-dependent synaptic strength and uncover neuronal NgR1 as a regulator of synaptic plasticity.

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“…Among environmental mechanisms limiting CNS axonal growth are a number of myelin-associated proteins (1)(2)(3)(4)(5) and inhibitory proteoglcyans of the extracellular matrix (6)(7)(8). Modification of the CNS milieu enhances the sprouting or regeneration of several classes of axons (5,9,10).…”

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confidence: 99%

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

Hollis

Jamshidi

Löw

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

125

104

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Several experimental manipulations of the CNS environment successfully elicit regeneration of sensory and bulbospinal motor axons but fail to elicit regeneration of corticospinal axons, suggesting that cell-intrinsic mechanisms limit the regeneration of this critical class of motor neurons. We hypothesized that enhancement of intrinsic neuronal growth mechanisms would enable adult corticospinal motor axon regeneration. Lentiviral vectors were used to overexpress the BDNF receptor trkB in layer V corticospinal motor neurons. After subcortical axotomy, trkB transduction induced corticospinal axon regeneration into subcortical lesion sites expressing BDNF. In the absence of trkB overexpression, no regeneration occurred. Selective deletion of canonical, trkB-mediated neurite outgrowth signaling by mutation of the Shc/FRS-2 activation domain prohibited Erk activation and eliminated regeneration. These findings support the hypothesis that the refractory regenerative state of adult corticospinal axons can be attributed at least in part to neuron-intrinsic mechanisms, and that activation of ERK signaling can elicit corticospinal tract regeneration.BDNF ͉ intrinsic ͉ retrograde infection ͉ subcortical lesion

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White matter inhibitors in CNS axon regeneration failure

Cited by 90 publications

References 98 publications

Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation

Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation

Synaptic Function for the Nogo-66 Receptor NgR1: Regulation of Dendritic Spine Morphology and Activity-Dependent Synaptic Strength

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

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