Abstract：
BACKGROUND: Elevated intracranial pressure (ICP) accompanying a number of neurological emergencies is poorly understood, and lacks a model to determine cellular pathophysiology. This limits our ability to identify cellular and molecular biomarkers associated with the pathological progression from physiologic to pathologic ICP.
UNASSIGNED: We developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC3I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48h to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury.
RESULTS: Compared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes.
UNASSIGNED: Cell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained.
CONCLUSIONS: This model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP.
UNASSIGNED: We developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC3I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48h to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury.
RESULTS: Compared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes.
UNASSIGNED: Cell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained.
CONCLUSIONS: This model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP.
摘要：
背景：颅内压（ICP）升高伴随着许多神经系统急症，并且缺乏确定细胞病理生理学的模型。这限制了我们识别与从生理到病理ICP的病理进展相关的细胞和分子生物标志物的能力。
■我们开发了一种压力诱发脑损伤的离体模型，它结合了3D神经细胞培养和新开发的压力控制细胞培养培养箱（PC3I）。维持在3D肽缀合的藻酸盐水凝胶中的人星形胶质细胞和神经元经受模拟ICP的生理和病理水平的压力长达48小时,以评估分离压力对细胞活力的最早影响并量化压力诱导的细胞损伤的早期指标。
结果：与在生理压力下生长的对照细胞培养物相比，持续的病理压力暴露以细胞特异性方式增加了细胞内ATP的释放.18小时的持续压力导致从神经元而不是星形胶质细胞释放的ATP增加。
■细胞培养培养箱在正常大气压下维持培养。基于多个文献检索，我们不知道任何其他细胞培养箱系统可以改变维持原代CNS细胞的压力。
结论：该模型模拟了脑积水患者颅内压升高的临床特征，并提供了在新生儿脑积水最早进展期间遇到的病理信号的第一个估计。该模型应提供更好地理解与升高的ICP的最早阶段相关的病理生物标志物的手段。
■我们开发了一种压力诱发脑损伤的离体模型，它结合了3D神经细胞培养和新开发的压力控制细胞培养培养箱（PC3I）。维持在3D肽缀合的藻酸盐水凝胶中的人星形胶质细胞和神经元经受模拟ICP的生理和病理水平的压力长达48小时,以评估分离压力对细胞活力的最早影响并量化压力诱导的细胞损伤的早期指标。
结果：与在生理压力下生长的对照细胞培养物相比，持续的病理压力暴露以细胞特异性方式增加了细胞内ATP的释放.18小时的持续压力导致从神经元而不是星形胶质细胞释放的ATP增加。
■细胞培养培养箱在正常大气压下维持培养。基于多个文献检索，我们不知道任何其他细胞培养箱系统可以改变维持原代CNS细胞的压力。
结论：该模型模拟了脑积水患者颅内压升高的临床特征，并提供了在新生儿脑积水最早进展期间遇到的病理信号的第一个估计。该模型应提供更好地理解与升高的ICP的最早阶段相关的病理生物标志物的手段。
