Carbamylated Erythropoietin Decreased Proliferation and Neurogenesis in the Subventricular Zone, but Not the Dentate Gyrus, After Irradiation to the Developing Rat Brain.
Carbamylated Erythropoietin Decreased Proliferation and Neurogenesis in the Subventricular Zone, but Not the Dentate Gyrus, After Irradiation to the Developing Rat Brain.
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DOI：
10.3389/fneur.2018.00738
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发表时间：
2018
影响因子：
3.4
通讯作者：
Blomgren K
中科院分区：
文献类型：
--
作者：
Osato K;Sato Y;Osato A;Sato M;Zhu C;Leist M;Kuhn HG;Blomgren K
小儿脑肿瘤的颅脑放射治疗会引起进行性的、使人衰弱的晚期效应，包括认知能力下降。促红细胞生成素（EPO）已被证明是神经保护和促进神经再生。氨甲酰化促红细胞生成素（CEPO）保留了EPO的保护特性，但不是促红细胞生成的。为了研究CEPO对暴露于放射治疗的发育中的脑的影响，将6戈伊的单次照射（IR）剂量施用到出生后9天（P9）的大鼠的脑，并将CEPO（40 μg/kg s.c.）在P8、P9、P11、P13和P15注射。为了检查增殖，在P15、P16和P17注射5-溴-2-脱氧尿苷（BrdU）。最后一次注射BrdU后7天，CEPO给药并不影响海马颗粒细胞层（GCL）或室下区（SVZ）中BrdU的掺入，而IR使GCL和SVZ中的BrdU掺入分别减少了63%和18%。CEPO并没有影响BrdU掺入GCL的照射大脑，虽然它是进一步减少（31%）的SVZ。为了评估CEPO对神经发生的影响，定量BrdU/doublecortin双阳性细胞。CEPO没有影响神经发生在非辐射的大脑，而IR减少神经发生的58%，在齿状回（DG），但没有影响它在SVZ。在DG中，CEPO不影响IR后的神经发生率，而在SVZ中，IR后的神经发生率与溶剂处理大鼠的神经发生率相比下降了30%。CEPO和IR都没有改变小胶质细胞的数量。总之，CEPO并没有促进非辐射或辐射大鼠脑的神经发生，甚至加重了SVZ的神经发生减少。这引起了人们对放射治疗后使用EPO相关化合物的担忧。
Cranial radiotherapy for pediatric brain tumors causes progressive, debilitating late effects, including cognitive decline. Erythropoietin (EPO) has been shown to be neuroprotective and to promote neuroregeneration. Carbamylated erythropoietin (CEPO) retains the protective properties of EPO but is not erythrogenic. To study the effects of CEPO on the developing brain exposed to radiotherapy, a single irradiation (IR) dose of 6 Gy was administered to the brains of postnatal day 9 (P9) rats, and CEPO (40 μg/kg s.c.) was injected on P8, P9, P11, P13, and P15. To examine proliferation, 5-Bromo-2-deoxyuridine (BrdU) was injected on P15, P16, and P17. CEPO administration did not affect BrdU incorporation in the granule cell layer (GCL) of the hippocampus or in the subventricular zone (SVZ) as quantified 7 days after the last BrdU injection, whereas IR decreased BrdU incorporation in the GCL and SVZ by 63% and 18%, respectively. CEPO did not affect BrdU incorporation in the GCL of irradiated brains, although it was reduced even further (to 31%) in the SVZ. To evaluate the effect of CEPO on neurogenesis, BrdU/doublecortin double-positive cells were quantified. CEPO did not affect neurogenesis in non-irradiated brains, whereas IR decreased neurogenesis by 58% in the dentate gyrus (DG) but did not affect it in the SVZ. In the DG, CEPO did not affect the rate of neurogenesis following IR, whereas in the SVZ, the rate decreased by 30% following IR compared with the rate in vehicle-treated rats. Neither CEPO nor IR changed the number of microglia. In summary, CEPO did not promote neurogenesis in non-irradiated or irradiated rat brains and even aggravated the decreased neurogenesis in the SVZ. This raises concerns regarding the use of EPO-related compounds following radiotherapy.
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影响因子：
82.9
作者：
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通讯作者：
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影响因子：
45.3
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