雌性和雄性大鼠创伤性脑损伤(TBI)模型中反复轻度体重下降和侧液叩击伤的组织学比较。

IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE SHOCK Pub Date : 2024-09-01 Epub Date: 2024-05-23 DOI:10.1097/SHK.0000000000002395
Sydney M Vita, Shealan C Cruise, Nicholas W Gilpin, Patricia E Molina
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引用次数: 0

摘要

摘要:在临床前创伤性脑损伤(TBI)研究中,应根据研究问题和感兴趣的结果指标选择动物模型。不同损伤模型的直接并排比较对于做出此类决定至关重要。在这里,我们使用免疫组化技术比较了两种常见的 TBI 模型的结果,即成年雌性和雄性 Wistar 大鼠的侧向脑液叩击(LFP)和反复轻度体重下降(rmWD)。具体而言,我们测量了 LFP 和 rmWD 对脑血管和紧密连接破坏、神经炎症、成熟神经元以及损伤部位皮质、损伤邻近皮质、齿状回和海马 CA2/3 区神经元周围网的标记物的影响。动物被随机分为 LFP 组和 rmWD 组。第 1 天,LFP 组接受开颅手术,第 4 天接受损伤(或假手术;随机分配)。rmWD动物在这4天中的每一天都接受了损伤或仅异氟醚治疗(随机分配)。损伤七天后,收获大脑进行分析。总体而言,我们的观察结果表明,LFP造成的破坏最为明显,其次是单纯开颅手术,而与单纯异氟醚对照组相比,rmWD动物表现出的残余变化最小,这支持了将rmWD视为轻度损伤的观点。LFP 会导致更持久的破坏,也许更能代表中度创伤性脑损伤。我们还报告了开颅手术和 LFP 对女性造成的损伤大于男性。这些发现将有助于该领域根据伤后结果的目标严重程度选择动物模型,并支持将两性和适当的对照组纳入其中。
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HISTOLOGICAL COMPARISON OF REPEATED MILD WEIGHT DROP AND LATERAL FLUID PERCUSSION INJURY MODELS OF TRAUMATIC BRAIN INJURY IN FEMALE AND MALE RATS.

Abstract: In preclinical traumatic brain injury (TBI) research, the animal model should be selected based on the research question and outcome measures of interest. Direct side-by-side comparisons of different injury models are essential for informing such decisions. Here, we used immunohistochemistry to compare the outcomes from two common models of TBI, lateral fluid percussion (LFP) and repeated mild weight drop (rmWD) in adult female and male Wistar rats. Specifically, we measured the effects of LFP and rmWD on markers of cerebrovascular and tight junction disruption, neuroinflammation, mature neurons, and perineuronal nets in the cortical site of injury, cortex adjacent to injury, dentate gyrus, and the CA 2/3 area of the hippocampus. Animals were randomized into the LFP or rmWD group. On day 1, the LFP group received a craniotomy, and on day 4, injury (or sham procedure; randomly assigned). The rmWD animals underwent either injury or isoflurane only (randomly assigned) on each of those 4 days. Seven days after injury, brains were harvested for analysis. Overall, our observations revealed that the most significant disruptions were evident in response to LFP, followed by craniotomy only, whereas rmWD animals showed the least residual changes compared with isoflurane-only controls, supporting consideration of rmWD as a mild injury. LFP led to longer-lasting disruptions, perhaps more representative of moderate TBI. We also report that craniotomy and LFP produced greater disruptions in females relative to males. These findings will assist the field in the selection of animal models based on target severity of postinjury outcomes and support the inclusion of both sexes and appropriate control groups.

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来源期刊
SHOCK
SHOCK 医学-外科
CiteScore
6.20
自引率
3.20%
发文量
199
审稿时长
1 months
期刊介绍: SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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