Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Immunol. 2022 Feb 9;13:753570. doi: 10.3389/fimmu.2022.753570. eCollection 2022.
Traumatic brain injury is a leading cause of injury-related death and morbidity. Multiple clinical and pre-clinical studies have reported various results regarding sex-based differences in TBI. Our accepted rodent model of traumatic brain injury was used to identify sex-based differences in the pathological features of TBI.
Male and female Sprague-Dawley rats were subjected to either controlled-cortical impact (CCI) or sham injury; brain tissue was harvested at different time intervals depending on the specific study. Blood-brain barrier (BBB) analysis was performed using infrared imaging to measure fluorescence dye extravasation. Microglia and splenocytes were characterized with traditional flow cytometry; microglia markers such as CD45, P2Y12, CD32, and CD163 were analyzed with t-distributed stochastic neighbor embedding (t-SNE). Flow cytometry was used to study tissue cytokine levels, and supplemented with ELISAs of TNF-⍺, IL-17, and IL-1β of the ipsilateral hemisphere tissue.
CCI groups of both sexes recorded a higher BBB permeability at 72 hours post-injury than their respective sham groups. There was significant difference in the integrated density value of BBB permeability between the male CCI group and the female CCI group (female CCI mean = 3.08 x 108 ± 2.83 x 107, male CCI mean = 2.20 x 108 ± 4.05 x 106, p = 0.0210), but otherwise no differences were observed. Traditional flow cytometry did not distinguish any sex-based difference in regards to splenocyte cell population after CCI. t-SNE did not reveal any significant difference between the male and female injury groups in the activation of microglia. Cytokine analysis after injury by flow cytometry and ELISA was limited in differences at the time point of 6 hours post-injury.
In our rodent model of traumatic brain injury, sex-based differences in pathology and neuroinflammation at specified time points are limited, and only noted in one specific analysis of BBB permeability.
创伤性脑损伤是与损伤相关的死亡和发病率的主要原因。多项临床和临床前研究报告了创伤性脑损伤中基于性别的差异的各种结果。我们使用公认的创伤性脑损伤啮齿动物模型来确定创伤性脑损伤的病理特征中的基于性别的差异。
雄性和雌性 Sprague-Dawley 大鼠分别接受控制性皮质撞击（CCI）或假损伤；根据特定研究，在不同时间间隔收获脑组织。使用红外成像测量荧光染料外渗来进行血脑屏障（BBB）分析。使用传统流式细胞术对小胶质细胞和脾细胞进行特征描述；使用 t 分布随机邻域嵌入（t-SNE）分析小胶质细胞标志物如 CD45、P2Y12、CD32 和 CD163。流式细胞术用于研究组织细胞因子水平，并补充同侧半球组织的 TNF- ⍺、IL-17 和 IL-1β 的 ELISA。
两种性别的 CCI 组在损伤后 72 小时的 BBB 通透性均高于各自的假损伤组。雄性 CCI 组和雌性 CCI 组的 BBB 通透性的积分密度值之间存在显著差异（雌性 CCI 平均值=3.08 x 108 ± 2.83 x 107，雄性 CCI 平均值=2.20 x 108 ± 4.05 x 106，p = 0.0210），但除此之外，没有观察到差异。传统流式细胞术未能区分 CCI 后脾细胞群体中的任何基于性别的差异。t-SNE 未显示雄性和雌性损伤组之间小胶质细胞激活的任何显著差异。通过流式细胞术和 ELISA 分析损伤后的细胞因子在 6 小时后损伤时间点的差异有限。
在我们的创伤性脑损伤啮齿动物模型中，特定时间点的病理学和神经炎症中的基于性别的差异是有限的，并且仅在 BBB 通透性的一个特定分析中注意到。
