Plasmalemma permeability and necrotic cell death phenotypes after intracerebral hemorrhage in mice.
Plasmalemma permeability and necrotic cell death phenotypes after intracerebral hemorrhage in mice.
复制标题
小鼠脑出血后的血浆膜通透性和坏死细胞死亡表型。
DOI：
10.1161/strokeaha.111.635672
复制
发表时间：
2012-02
期刊：
影响因子：
8.3
通讯作者：
Whalen MJ
中科院分区：
文献类型：
--
作者：
Zhu X;Tao L;Tejima-Mandeville E;Qiu J;Park J;Garber K;Ericsson M;Lo EH;Whalen MJ
Traumatic and ischemic brain injury induce plasmalemma permeability and necrosis however no studies have examined these aspects of cellular injury in intracerebral hemorrhage (ICH) models. In vivo propidium iodide (PI) and YOYO-1 were used to assess plasmalemma damage after collagenase-induced ICH in mice. Ex vivo aspartylglutamylvalylaspartic acid (DEVD), TUNEL, and electron microscopy were used to assess the relationship between plasmalemma permeability and mode of cell death. Cell types vulnerable to plasmalemma damage were determined by immunohistochemistry. Plasmalemma permeability was first detected in the lesion at 1–3 h and peaked at 48–72 h. Neurons and IBA-1-positive cells with morphological features of monocytes were sensitive whereas resident microglia and astrocytes were resistant to plasmalemma permeability. PI+ cells colocalized with fluorescent labeled caspase substrates and TUNEL beginning at 3–6 h. At 48 h, greater than half of injured cells were PI+/DEVD− or PI+/TUNEL TUNEL− suggesting necrosis, and less than 5% were PI−/TUNEL+ or PI−/DEVD+. Electron microscopy confirmed ultrastructural features of necrosis at 24 h after ICH, HMGB1 was released from permeable cells, and mice deficient in RIPK3, a known necrosis trigger, had 50% less PI+ cells at 24 h. Permeable cells remained in brain for at least 24 h, with less than 10% spontaneous resealing. Necrosis contributes to cell demise after ICH. Programmed necrosis and plasmalemma damage may represent novel therapeutic targets to prevent cell death or rescue injured cells after ICH.
