Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Chang Gung Medical College and University, Taoyuan County 333, Taiwan.
Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung Medical College and University, Taoyuan County 333, Taiwan.
Int J Mol Sci. 2020 Aug 31;21(17):6291. doi: 10.3390/ijms21176291.
Traumatic brain injury (TBI) could result in edema and cause an increase in intracranial pressure of the brain resulting in mortality and morbidity. Although there is hyperosmolarity therapy available for this pathophysiological event, it remains controversial. Recently, several groups have shown docosahexaenoic acid (DHA) to improve functional and histological outcomes following brain injury based on reduction of neuroinflammation and apoptosis. However, the effect of DHA on blood-brain barrier (BBB) dysfunction after brain injury has not been fully studied. Here, a controlled cortical impact rat model was used to test the effect of a single dose of DHA administered 30 min post injury. Modified neurological severity score (mNSS) and forelimb asymmetry were used to determine the functional outcomes. Neuroimaging and histology were used to characterize the edema and BBB dysfunction. The study showed that DHA-treated TBI rats had better mNSS and forelimb asymmetry score than vehicle-treated TBI rats. Temporal analysis of edema using MRI revealed a significant reduction in edema level with DHA treatment compared to vehicle in TBI rats. Histological analysis using immunoglobulin G (IgG) extravasation showed that there was less extravasation, which corresponded with a reduction in aquaporin 4 and astrocytic metalloprotease 9 expression, and greater endothelial occludin expression in the peri-contusional site of the TBI rat brain treated with DHA in comparison to vehicle treatment. In conclusion, the study shows that DHA can exert its functional improvement by prevention of the edema formation via prevention of BBB dysfunction after TBI.
创伤性脑损伤（TBI）可导致水肿，并使脑内压升高，导致死亡率和发病率增加。尽管有高渗疗法可用于治疗这种病理生理事件，但仍存在争议。最近，一些研究小组发现二十二碳六烯酸（DHA）可通过减少神经炎症和细胞凋亡来改善脑损伤后的功能和组织学结果。然而，DHA 对脑损伤后血脑屏障（BBB）功能障碍的影响尚未得到充分研究。在这里，使用控制皮质撞击大鼠模型来测试损伤后 30 分钟给予单次剂量 DHA 的效果。改良神经严重程度评分（mNSS）和前肢不对称性用于确定功能结果。神经影像学和组织学用于描述水肿和 BBB 功能障碍。该研究表明，与 vehicle 治疗的 TBI 大鼠相比，DHA 治疗的 TBI 大鼠具有更好的 mNSS 和前肢不对称性评分。使用 MRI 进行的水肿时间分析显示，与 vehicle 相比，DHA 治疗的 TBI 大鼠的水肿水平显着降低。使用免疫球蛋白 G（IgG）漏出的组织学分析显示，DHA 治疗的 TBI 大鼠的损伤周边部位的漏出量较少，水通道蛋白 4 和星形胶质细胞金属蛋白酶 9 的表达减少，内皮 occludin 的表达增加。综上所述，该研究表明，DHA 可通过预防 TBI 后 BBB 功能障碍来防止水肿形成，从而发挥其功能改善作用。
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