PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury.
PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury.
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DOI：
10.1016/j.neulet.2014.02.039
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发表时间：
2014-06-24
影响因子：
2.5
通讯作者：
Xu XM
中科院分区：
文献类型：
--
作者：
Walker CL;Xu XM
颈脊髓损伤（SCI）损害与同侧前肢功能有关的轴突和运动神经元，并导致脱髓鞘和少突胶质细胞死亡。抑制磷酸酶和紧张素同源物PTEN，促进神经细胞在体内和体外的存活、神经保护和再生。PTEN抑制也可能通过Akt激活促进体外少突胶质细胞介导的轴突髓鞘形成。我们最近证明了磷酸酶PTEN抑制剂双氧钒(bpV)-pic的急性治疗减少了颈部半挫伤后的组织损伤和神经元死亡，并促进了功能恢复。有证据表明bpV可以促进髓磷脂的稳定性；然而，bpV对挫伤性脊髓损伤模型中髓鞘细胞和少突胶质细胞的影响尚不清楚。我们假设bpV可以通过保留或髓鞘再生来增加损伤部位周围的髓鞘，并且bpV治疗可能促进少突胶质细胞数量的增加。通过组织和免疫荧光标记，我们发现bpV治疗显著提高了白质（30%,p < 0.01）和Luxol Fast Blue (LFB)+髓鞘区吻侧（Veh: 0.56±0.01 vs. bpV: 0.64±0.02,p < 0.05）和震中（Veh: 0.4175±0.03 vs. bpV: 0.5400±0.03,p < 0.05）。bpV治疗的VLF少突胶质细胞也显著增加（109±5.3 vs. Veh: 77±2.7/mm2; p < 0.01）。此外，相对于假手术神经元的大小，bpV增加了运动神经元体细胞面积（1.0±0.02 vs. Veh: 0.77±0.02）。该研究提供了对其他细胞和组织效应的关键见解，这些效应可能有助于挫伤性颈椎脊髓损伤后bpv介导的功能恢复。
Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p < 0.01) and Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56 ± 0.01 vs. bpV: 0.64 ± 0.02; p < 0.05) and at the epicenter (Veh: 0.4175 ± 0.03 vs. bpV: 0.5400 ± 0.03; p < 0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109 ± 5.3 vs. Veh: 77 ± 2.7/mm2; p < 0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0 ± 0.02 vs. Veh: 0.77 ± 0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.
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影响因子：
82.9
作者：
Crowe, MJ;Bresnahan, JC;Beattie, MS
通讯作者：
Beattie, MS
影响因子：
5.3
作者：
Loy, DN;Magnuson, DSK;Whittemore, SR
通讯作者：
Whittemore, SR
DOI：
10.1523/jneurosci.0234-09.2009
发表时间：
2009-05-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Tyler WA;Gangoli N;Gokina P;Kim HA;Covey M;Levison SW;Wood TL
通讯作者：
Wood TL
影响因子：
11.2
作者：
Harrington, Emily P.;Zhao, Chao;Fancy, Stephen P. J.;Kaing, Sovann;Franklin, Robin J. M.;Rowitch, David H.
通讯作者：
Rowitch, David H.
影响因子：
11.2
作者：
Liu, NK;Zhang, YP;Xu, XM
通讯作者：
Xu, XM