Division of Anesthesiology and Critical Care, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
J Neurosurg Anesthesiol. 2011 Jul;23(3):222-8. doi: 10.1097/ANA.0b013e31821b536a.
The animal model of stroke that is most frequently used is a rat model of focal brain ischemia caused by middle cerebral artery occlusion (MCAO). Several studies have reported a link between levels of cell-free DNA (CFD) and neurologic outcome in human stroke. The purpose of this study was to assess brain injury and measure CFD levels in 2 models of MCAO in rats, and to determine whether brain injury correlates with CFD.
A total of 60 rats were used for this study. Twenty rats underwent a sham procedure, 20 rats had MCAO using a monofilament, and 20 rats had MCAO with a silicon-coated filament. Groups were further divided into 2 subgroups. In 1 subgroup of 10 rats, neurologic performance [measured as a neurologic severity score, (NSS)] was measured at 1 and 24 hours after the procedure, and brain edema and infarct volume were determined at 24 hours. In the second subgroup of 10 rats, CFD was measured at 0, 1, 2, 4, 8, 12, and 24 hours and at 2, 3, 4, and 5 days. Neurologic performance (measured as a NSS) was measured at 1 and 24 hours after the procedure.
The main finding was a significant increase in CFD levels observed 24 hours after the onset of MCAO. The correlation between the total infarct volume and CFD levels of the 3 groups was R=0.78, P<0.0001. Brain edema and NSS also were strongly correlated with CFD levels at 24 hours after MCAO (R=0.91, P<0.0001 and R=0.73, P<0.0001, respectively).
We found that CFD levels correlate well with the extent of ischemic injury, brain edema, and neurologic outcome in rats 24 hours post-MCAO. We have also shown that CFD correlates well with the expected temporal progression of ischemic injury. These findings place CFD in a unique place as a biomarker for stroke, both experimentally and possibly clinically.
最常使用的中风动物模型是由大脑中动脉闭塞（MCAO）引起的局灶性脑缺血大鼠模型。几项研究报告称，人类中风中细胞游离 DNA（CFD）水平与神经功能结局之间存在关联。本研究旨在评估两种 MCAO 大鼠模型中的脑损伤并测量 CFD 水平，并确定脑损伤是否与 CFD 相关。
本研究共使用了 60 只大鼠。20 只大鼠接受假手术，20 只大鼠使用单丝进行 MCAO，20 只大鼠使用硅涂层丝进行 MCAO。各组进一步分为 2 个亚组。在 10 只大鼠的 1 个亚组中，在手术后 1 小时和 24 小时测量神经功能表现（以神经严重程度评分[NSS]表示），并在 24 小时测量脑水肿和梗死体积。在另 10 只大鼠的第 2 个亚组中，在 0、1、2、4、8、12 和 24 小时以及 2、3、4 和 5 天时测量 CFD。在手术后 1 小时和 24 小时测量神经功能表现（以 NSS 表示）。
主要发现是在 MCAO 发作后 24 小时观察到 CFD 水平显著增加。3 组的总梗死体积与 CFD 水平之间的相关性为 R=0.78，P<0.0001。MCAO 后 24 小时的脑水肿和 NSS 与 CFD 水平也呈强相关（R=0.91，P<0.0001 和 R=0.73，P<0.0001）。
我们发现，CFD 水平与 MCAO 后 24 小时大鼠缺血性损伤、脑水肿和神经功能结局密切相关。我们还表明，CFD 与缺血性损伤的预期时间进展密切相关。这些发现使 CFD 作为一种生物标志物在实验和可能临床方面都处于独特的地位。
