Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China.
Department of Ultrasound, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Sci Rep. 2019 Sep 25;9(1):13838. doi: 10.1038/s41598-019-50188-y.
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.
脑组织的力学响应与脑血流和脑部疾病密切相关。在脑内出血（ICH）中，初始出血时会产生占位效应，导致组织明显变形。然而，与 ICH 后继发性脑损伤相比，针对占位效应相关的脑损伤机制和治疗方法的研究较少，这可能是因为缺乏可模拟占位效应的可接受的动物模型。因此，合成了一种温敏性聚（N-异丙基丙烯酰胺）（PNIPAM）水凝胶，并将其注入大鼠脑内，以建立用于占位效应研究的 ICH 模型。将 PNIPAM 水凝胶或自体血液注入大鼠脑内，建立 ICH 动物模型，评估占位容积、脑组织弹性、脑水肿、神经元细胞死亡、铁沉积和行为学恢复情况。PNIPAM 水凝胶的低临界溶液温度为 32°C，且其表面粗糙，具有与血凝块相似的形貌和孔结构。此外，接受 PNIPAM 和血液注射的 ICH 模型动物在脑组织中产生了相似的病变容积、弹性变化和机械激活离子通道压电 2 上调。同时，与血液模型相比，PNIPAM 水凝胶模型中观察到轻微的铁沉积、神经元细胞死亡和脑水肿。此外，通过皮下植入，PNIPAM 水凝胶在体内表现出良好的生物相容性和稳定性。我们的研究结果表明，PNIPAM 水凝胶脑内输注可以形成类似于血肿的占位效应，并最小化血液的干扰，建立占位效应 ICH 模型有助于理解原发性脑损伤的机制以及占位效应对 ICH 后继发性脑损伤的作用。
