Acute and Chronic Deficits in the Urinary Bladder after Spinal Contusion Injury in the Adult Rat
Acute and Chronic Deficits in the Urinary Bladder after Spinal Contusion Injury in the Adult Rat
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DOI：
10.1089/neu.2009.0997
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发表时间：
2010-02-01
影响因子：
4.2
通讯作者：
Grill, Raymond J.
中科院分区：
文献类型：
--
作者：
Herrera, Juan J.;Haywood-Watson, Ricky J. L., II;Grill, Raymond J.
创伤性脊髓损伤（SCI）永久性地改变了人类的膀胱功能。血尿和膀胱炎发生在人SCI以及SCI的啮齿动物模型中。其他人报告了早期SCI依赖性膀胱尿路上皮完整性破坏，导致尿液和尿源性物质的渗透性增加。这可能导致膀胱炎或膀胱炎症，这是一种在人类SCI慢性期存在的持续病理状态。我们的研究有两个目的：（1）开始使用临床相关的脊髓挫伤损伤模型来检查膀胱尿路上皮内发生的炎症和分子变化，以及（2）评估这些变化是否持续到SCI的慢性期。大鼠接受中度SCI或假手术。在7天内或7个月时从SCI和假手术受试者收集尿液，以评估排泄的蛋白质水平。通过生物化学和免疫组织化学方法评估膀胱壁的炎症。膀胱紧密连接蛋白，泌尿上皮完整性的介质，也被测量在急性和慢性阶段的SCI。SCI后尿蛋白和血红蛋白水平迅速升高。膀胱壁内中性粒细胞数量的SCI依赖性升高在48 h达到峰值。膀胱紧密连接蛋白表现出快速但短暂的减少早在2小时后SCI。令人惊讶的是，在慢性SCI中可以检测到尿蛋白水平升高和膀胱紧密连接蛋白的显著缺陷，这表明膀胱的早期病理变化可能在损伤的整个慢性阶段持续。
Traumatic spinal cord injury (SCI) permanently alters bladder function in humans. Hematuria and cystitis occur in both human SCI as well as in rodent models of SCI. Others have reported early SCI-dependent disruption to bladder uroepithelial integrity that results in increased permeability to urine and urine-borne substances. This can result in cystitis, or inflammation of the bladder, an ongoing pathological condition present throughout the chronic phase of SCI in humans. The goals of our study were twofold: (1) to begin to examine the inflammatory and molecular changes that occur within the bladder uroepithelium using a clinically-relevant spinal contusion model of injury, and (2) to assess whether these alterations continue into the chronic phase of SCI. Rats received either moderate SCI or sham surgery. Urine was collected from SCI and sham subjects over 7 days or at 7 months to assess levels of excreted proteins. Inflammation in the bladder wall was assessed via biochemical and immunohistochemical methods. Bladder tight junction proteins, mediators of uroepithelial integrity, were also measured in both the acute and chronic phases of SCI. Urine protein and hemoglobin levels rapidly increase following SCI. An SCI-dependent elevation in numbers of neutrophils within the bladder wall peaked at 48 h. Bladder tight junction proteins demonstrate a rapid but transient decrease as early as 2 h post-SCI. Surprisingly, elevated levels of urine proteins and significant deficits in bladder tight junction proteins could be detected in chronic SCI, suggesting that early pathological changes to the bladder may continue throughout the chronic phase of injury.