Background

Does minor head impact without signs of structural brain damage cause short-term changes in vasogenic edema as measured by an increase apparent diffusion coefficient (ADC) using diffusion weighted imaging? If so, could the increase in vasogenic edema be treated with a vasopressin V1a receptor antagonist? We hypothesized that SRX251, a highly selective V1a antagonist, would reduce vasogenic edema in response to a single minor head impact.

Methods

Lightly anesthetized male rats were subjected to a sham procedure or a single hit to the forehead using a closed skull, momentum exchange model. Animals recovered in five min and were injected with saline vehicle (n = 8) or SRX251 (n = 8) at 15 min post head impact and again 7−8 hrs later. At 2 h, 6 h, and 24 h post injury, rats were anesthetized and scanned for increases in ADC, a neurological measure of vasogenic edema. Sham rats (n = 6) were exposed to anesthesia and scanned at all time points but were not hit or treated. Images were registered to and analyzed using a 3D MRI rat atlas providing site-specific data on 150 different brain areas. These brain areas were parsed into 11 major brain regions.

Results

Untreated rats with brain injury showed a significant increase in global brain vasogenic edema as compared to sham and SRX251 treated rats. Edema peaked at 6 h in injured, untreated rats in three brain regions where changes in ADC were observed, but returned to sham levels by 24 h. There were regional variations in the time course of vasogenic edema and drug efficacy. Edema was significantly reduced in cerebellum and thalamus with SRX251 treatment while the basal ganglia did not show a response to treatment.

Conclusion

A single minor impact to the forehead causes regional increases in vasogenic edema that peak at 6 h but return to baseline within a day in a subset of brain regions. Treatment with a selective V1a receptor antagonist can reduce much of the edema.

中文翻译：

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轻微头部撞击后早期血管源性水肿的证据，可以用加压素 V1a 受体拮抗剂减轻

背景

没有结构性脑损伤迹象的轻微头部撞击是否会导致血管源性水肿的短期变化，如使用扩散加权成像通过增加的表观扩散系数 (ADC) 测量的？如果是这样，血管源性水肿的增加可以用加压素 V1a 受体拮抗剂治疗吗？我们假设 SRX251 是一种高度选择性的 V1a 拮抗剂，可以减少对单个轻微头部撞击的血管源性水肿。

方法

使用封闭的头骨动量交换模型对轻度麻醉的雄性大鼠进行假手术或单次击打前额。动物在五分钟内恢复，并在头部撞击后 15 分钟和 7-8 小时后再次注射盐水载体（n = 8）或 SRX251（n = 8）。在损伤后 2 小时、6 小时和 24 小时，对大鼠进行麻醉并扫描 ADC（血管源性水肿的神经学测量指标）的增加情况。假大鼠 (n = 6) 暴露在麻醉下并在所有时间点进行扫描，但没有受到打击或治疗。使用 3D MRI 大鼠图谱注册和分析图像，提供 150 个不同大脑区域的特定部位数据。这些大脑区域被解析为 11 个主要大脑区域。

结果

与假手术和 SRX251 治疗的大鼠相比，未治疗的脑损伤大鼠显示整体脑血管源性水肿显着增加。在观察到 ADC 变化的三个大脑区域中，受伤、未经治疗的大鼠的水肿在 6 小时达到峰值，但在 24 小时后恢复到假手术水平。血管源性水肿的时间进程和药物疗效存在区域差异。SRX251 治疗后小脑和丘脑的水肿显着减少，而基底神经节对治疗没有反应。

结论

对前额的一次轻微撞击会导致血管源性水肿的局部增加，在 6 小时达到峰值，但在一天内在一部分大脑区域中恢复到基线。用选择性 V1a 受体拮抗剂治疗可以减轻大部分水肿。