Askarifirouzjaei Hadi, Khajoueinejad Leila, Wei Elena, Cheruvu Sruti, Ayala Carlos, Chiang Ning, Theis Thomas, Sun Dongming, Fazeli Mehdi, Young Wise
Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08554, USA.
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Pathophysiology. 2023 Jul 11;30(3):275-295. doi: 10.3390/pathophysiology30030023.
Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic changes in the bladder. We analyzed the urine of male and female Sprague-Dawley and Fischer 344 rats after experimental spinal cord contusion, including unstained microscopic inspections of the urine, differential white blood cell counts colored by the Wright stain, and total leukocyte counts using fluorescent nuclear stains. We examined bladder histological changes in acute and chronic phases of SCI, using principal component analysis (PCA) and clustered heatmaps of Pearson correlation coefficients to interpret how measured variables correlated with each other. Male rats showed a distinct pattern of macroscopic hematuria after spinal cord injury. They had higher numbers of red blood cells with significantly more leukocytes and neutrophils than female rats, particularly hypersegmented neutrophils. The histological examination of the bladders revealed a distinct line of apoptotic umbrella cells and disrupted bladder vessels early after SCI and progressive pathological changes in multiple bladder layers in the chronic phase. Multivariate analyses indicated immune cell infiltration in the bladder, especially hypersegmented neutrophils, that correlated with red blood cell counts in male rats. Our study highlights a hitherto unreported sex difference of hematuria and pathological changes in males and females' bladders after SCI, suggesting an important role of immune cell infiltration, especially neutrophils, in SCI-induced hemorrhagic cystitis.
脊髓损伤（SCI）后，大鼠会出现一种名为出血性膀胱炎的病症。这种病症的机制尚不清楚，但在雄性大鼠中比在雌性大鼠中更为严重。我们评估了性别在出血性膀胱炎及膀胱病理慢性变化方面的作用。我们分析了实验性脊髓挫伤后雄性和雌性斯普拉格-道利大鼠及费希尔344大鼠的尿液，包括尿液的未染色显微镜检查、经瑞氏染色的白细胞分类计数以及使用荧光核染色的白细胞总数计数。我们使用主成分分析（PCA）和皮尔逊相关系数的聚类热图来解释测量变量之间的相互关系，从而研究脊髓损伤急性和慢性阶段膀胱的组织学变化。雄性大鼠在脊髓损伤后呈现出明显的肉眼血尿模式。它们的红细胞数量更多，白细胞和中性粒细胞数量显著多于雌性大鼠，尤其是多分叶核中性粒细胞。膀胱的组织学检查显示，脊髓损伤后早期有明显的凋亡伞细胞线和膀胱血管破坏，慢性期膀胱多层出现进行性病理变化。多变量分析表明膀胱中有免疫细胞浸润，尤其是多分叶核中性粒细胞，这与雄性大鼠的红细胞计数相关。我们的研究突出了脊髓损伤后雄性和雌性膀胱血尿及病理变化迄今未报道的性别差异，表明免疫细胞浸润，尤其是中性粒细胞，在脊髓损伤诱导的出血性膀胱炎中起重要作用。
