Aquaporins in spinal cord injury: the janus face of aquaporin 4.
Aquaporins in spinal cord injury: the janus face of aquaporin 4.
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DOI：
10.1016/j.neuroscience.2010.01.037
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发表时间：
2010-07-28
期刊：
影响因子：
3.3
通讯作者：
Lee, J.
中科院分区：
文献类型：
--
作者：
Nesic, O.;Guest, J. D.;Zivadinovic, D.;Narayana, P. A.;Herrera, J. J.;Grill, R. J.;Mokkapati, V. U. L.;Gelman, B. B.;Lee, J.
关键词：
虽然脊髓水通道(Aquaporins，AQP)功能障碍可能是脊髓损伤(SCI)后离子/水平衡严重失调的原因之一，但对其作用仍知之甚少。在这里，我们报道并讨论了AQP4在人类脊髓损伤中表达的变化的潜在意义，该变化产生了不含AQP4的GFAP标记的星形胶质细胞和高表达AQP4的GFAP标记的星形胶质细胞。我们使用大鼠脊髓挫伤模型来研究观察到的人类脊髓损伤的变化。AQP4阴性的星形胶质细胞可能是在脊髓损伤诱导的星形胶质细胞修复过程中产生的，但其来源和在脊髓损伤中的作用仍有待研究。我们发现，AQP4的过度表达很可能是由缺氧引发的。我们对损伤的大鼠脊髓的转录图谱表明，AQP4介导的水内流增加伴随着氯离子和钾离子的吸收增加，这代表了星形胶质细胞对低氧的保护性反应。然而，不平衡的水分摄入也会导致星形细胞肿胀，这可能会导致运动障碍，但可能只会造成较轻微的损伤。在重度脊髓损伤大鼠，运动恢复期AQP4高表达的星形胶质细胞低丰度。我们的结果表明，严重的大鼠脊髓挫伤是分析脊髓损伤后AQP4功能的较好模型。我们发现，AQP4在慢性损伤后阶段的增加与脊髓损伤大鼠疼痛行为的发展有关，而导致疼痛发展的可能机制可能涉及星形细胞肿胀诱导的谷氨酸释放。相反，脊髓损伤后较晚发生的充液空洞的形成和大小似乎不受AQP4水平升高的程度的影响。因此，针对AQP4的治疗干预效果不仅取决于脊髓损伤或动物模型后的时间间隔，还取决于AQP4在缺氧中的保护作用和持续的星形细胞肿胀的有害影响之间的平衡。
Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates GFAP-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study observed changes in human SCI. AQP4-negative astrocytes are likely generated during the process of SCI-induced replacement of lost astrocytes, but their origin and role in SCI remains to be investigated. We found that AQP4-overexpression is likely triggered by hypoxia. Our transcriptional profiling of injured rat cords suggests that elevated AQP4-mediated water influx accompanies increased uptake of chloride and potassium ions which represents a protective astrocytic reaction to hypoxia. However, unbalanced water intake also results in astrocytic swelling that can contribute to motor impairment, but likely only in milder injuries. In severe rat SCI, a low abundance of AQP4-overexpressing astrocytes was found during the motor recovery phase. Our results suggest that severe rat contusion SCI is a better model to analyze AQP4 functions after SCI. We found that AQP4 increases in the chronic post-injury phase are associated with the development of pain-like behavior in SCI rats, while possible mechanisms underlying pain development may involve astrocytic swelling-induced glutamate release. In contrast, the formation and size of fluid-filled cavities occurring later after SCI does not appear to be affected by the extent of increased AQP4 levels. Therefore, the effect of therapeutic interventions targeting AQP4 will depend not only on the time interval after SCI or animal models, but also on the balance between protective role of increased AQP4 in hypoxia and deleterious effects of ongoing astrocytic swelling.
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影响因子：
3.3
作者：
Gwak, Y. S.;Hulsebosch, C. E.
通讯作者：
Hulsebosch, C. E.
DOI：
10.1016/j.bbrc.2009.09.015
发表时间：
2009-12-25
影响因子：
3.1
作者：
Kikuchi, Kiyoshi;Tancharoen, Salunya;Kawahara, Ko-ichi
通讯作者：
Kawahara, Ko-ichi
影响因子：
7.4
作者：
Carlton SM;Du J;Tan HY;Nesic O;Hargett GL;Bopp AC;Yamani A;Lin Q;Willis WD;Hulsebosch CE
通讯作者：
Hulsebosch CE
影响因子：
5.3
作者：
Guest, JD;Hiester, ED;Bunge, RP
通讯作者：
Bunge, RP
影响因子：
7.4
作者：
Cho, HY;Reddy, SP;Kleeberger, SR
通讯作者：
Kleeberger, SR