Ceftriaxone Preconditioning Confers Neuroprotection in Neonatal Rats Through Glutamate Transporter 1 Upregulation
Ceftriaxone Preconditioning Confers Neuroprotection in Neonatal Rats Through Glutamate Transporter 1 Upregulation
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DOI：
10.1177/1933719111410710
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发表时间：
2011-12-01
影响因子：
2.9
通讯作者：
Kimura, Tadashi
中科院分区：
文献类型：
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作者：
Mimura, Kazuya;Tomimatsu, Takuji;Kimura, Tadashi
目的：探讨头孢曲松预处理通过上调谷氨酸转运蛋白1 （GLT-1）改善新生动物脑损伤的假说。研究设计：从出生后第2天（P2）开始，用头孢曲松、红霉素、米诺环素或生理盐水连续5天预处理Sprague Dawley大鼠，检测P7脑内GLT-1/谷氨酸-天冬氨酸转运体（GLAST）信使RNA （mRNA）和蛋白水平。经头孢曲松或生理盐水预处理后，P7大鼠进行缺氧缺血（H-I）或假手术。术后1周（P14），采用苏木精-伊红染色、微管相关蛋白2 （MAP-2）免疫染色和转移酶介导的三磷酸脱氧尿苷刻痕末端标记（TUNEL）检测神经元损伤和可能的神经毒性。结果：反复注射头孢曲松可显著提高GLT-1 mRNA和蛋白水平，但对GLAST无显著影响。经此治疗和H-I处理后，map -2阳性面积增加，tunel阳性细胞减少。结论：产前头孢曲松可能有助于对未成熟大脑提供神经保护，成为临床围产期医学预防新生儿脑病的新策略。
Objective: This study investigated the hypothesis that ceftriaxone preconditioning ameliorates brain damage in neonatal animals through glutamate transporter 1 (GLT-1) upregulation. Study design: Sprague Dawley rats were pretreated with ceftriaxone, erythromycin, minocycline, or saline for 5 consecutive days starting from postnatal day 2 (P2), and GLT-1/glutamate-aspartate transporter (GLAST) messenger RNA (mRNA) and protein levels were examined in the P7 brains. After ceftriaxone or saline preconditioning, the P7 rats underwent hypoxic-ischemic (H-I) procedure or sham operation. One week after the procedure (P14), hematoxylin-eosin staining, microtubule-associated protein 2 (MAP-2) immunostaining, and transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay were used to examine neuronal damage and possible neurotoxicity. Results: Repeated ceftriaxone injections significantly increased GLT-1 mRNA and protein levels but not GLAST. Following such treatment and H-I procedure, the MAP-2-positive area increased and TUNEL-positive cells decreased. Conclusion: Antenatal ceftriaxone may help to provide neuroprotection in the immature brain and become a new prophylactic strategy to reduce neonatal encephalopathy in clinical perinatal medicine.