虚血性脳浮腫の最近の進歩

Recent advances in the research on ischemic brain edema

虚血性脳浮腫はKlatzoの脳浮腫分類による細胞障害性浮腫がまず出現し，血液脳関門破綻とともに血管原性脳浮腫が加わると考えられている。虚血急性期には電解質の能動的取り込みも浮腫生成に関与している可能性がある。細胞障害性浮腫は虚血直後から生じ，アストロサイトの膨化が主な変化だが，近年注目されている水分子チャンネルタンパク質アクアポリン4がアストロサイト血管足などに分布し，虚血性脳浮腫の生成・消退に密接に関与していると思われる。虚血発症12時間後くらいから血液脳関門が破綻し病巣への電解質，血漿タンパク質，さらに炎症細胞やサイトカインの流入が加わり浮腫が増悪する。血液脳関門の破綻の機序として，マトリックスメタロプロテイナーゼによる細胞基底膜の破綻が注目されている。今日の虚血性脳浮腫の病態研究と可逆的損傷期の診断に，MRI拡散画像法の果たした役割は大きい。

Ischemic brain edema is one of the most common type of brain edema. The pathomechanism of ischemic edema is heterogeneous depending on the intensity/duration of ischemia, time after onset of ischemia and occurrence/absence of blood flow restoration. Initial event in the ischemic edema is swelling of astrocytic endfeet paralleled to tissue energy failure, which gradually turned to irreversible（cytotoxic edema）. Recent studies on the water channel protein aquaporin family indicate that aquaporin 4, distributed in the astrocytic vascular endfeet is important in the formation and resolution of ischemic brain edema. After ischemic injury to vascular wall, vasogenic edema superimposed to the cytotoxic edema. Extravasation of electrolytes, macromolecules, inflammatory cells and cytokines significantly exaggerates ischemic edema. Important roles of matrix metalloproteinase in the evolution of vasogenic component of ischemic brain edema is a recent topic in the brain edema research. Fatal massive edema after middle cerebral artery occlusion was named“malignant edema”, and the mechanism has been intensively investigated. MRI diffusion imaging was a powerful tool in the investigation of ischemic brain edema. The detection of postischemic lesion at the time still reversible from necrosis is a most important contribution of the new imaging method. Brain edema is a pathological process taking place mainly in the extracellular space and in the white matter. Studies focused on pathomechanism at the tissue/cellular level rather than subcellular level using large-sized animal which has brain strucuture similar to human will be important in the future brain edema research.