课题组前期研究发现，体外净水压力会导致神经元活力、树突和轴突长度显著降低，但目前并没有适用于ICH占位效应研究的动物模型，该模型既需要与血肿具有物理和生物相容性，又需要能避免血液降解产物的毒性作用。基于此，课题组筛选出与血肿具有高度物理和生物相容性的材料，采用温敏性水凝胶聚（N-异丙基丙烯酰胺）（Poly (N-isopropylacrylamide), PNIPAM）构建了用于占位效应研究的动物模型，并与血液注射模型比较验证了该模型用于占位效应研究的可行性。

该课题由宫玉华同学完成。发表在Scientific Reports。

https://www.nature.com/articles/s41598-019-50188-y

Abstract

The mechanical response of brain tissue closely relates to cerebral blood flow and brain diseases. During intracerebral haemorrhage (ICH), a mass effect occurs during the initial bleeding and results in significant tissue deformation. However, fewer studies have focused on the brain damage mechanisms and treatment approaches associated with mass effects compared to the secondary brain injuries after ICH, which may be a result of the absence of acceptable animal models mimicking a mass effect. Thus, a thermo-sensitive poly (N-isopropylacrylamide) (PNIPAM) hydrogel was synthesized and injected into the rat brain to establish an ICH model for mass effect research. The PNIPAM hydrogel or autologous blood was injected to establish an ICH animal model, and the space-occupying volumes, brain tissue elasticity, brain oedema, neuronal cell death, iron deposition and behavioural recovery were evaluated. The lower critical solution temperature of PNIPAM hydrogel was 32 °C, and the PNIPAM hydrogel had a rough surface with similar topography and pore structure to a blood clot. Furthermore, the ICH model animals who received an injection of PNIPAM and blood produced similar lesion volumes, elasticity changes and mechanically activated ion channel piezo-2 upregulation in brain tissue. Meanwhile, slight iron deposition, neuronal cell death and brain oedema were observed in the PNIPAM hydrogel model compared to the blood model. In addition, the PNIPAM hydrogel showed good biocompatibility and stability in vivo via subcutaneous implantation. Our findings show that PNIPAM hydrogel cerebral infusion can form a mass effect similar to haematoma and minimize the interference of blood, and the establishment of a mass effect ICH model is beneficial for understanding the mechanism of primary brain injury and the role of mass effects in secondary brain damage after ICH.