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.
Highlights
intracerebral haemorrhage (ICH) has high mortality and morbidity, which includes primary and secondary brain injury according to the progression of the disease[5,6,7,8]
No clinical condition is affected only by mass effect without any secondary damage, and the haematoma may retract and resolve in long-term metabolism; the establishment of a mass effect ICH model is beneficial to understand the mechanism of primary brain injury after ICH
There are no clinical conditions that are affected only by mass effect without any secondary damage, the establishment of a mass effect ICH model is beneficial to understand the mechanism of primary brain injury and the role of mass effect in secondary brain damage after ICH
Summary
ICH has high mortality and morbidity, which includes primary and secondary brain injury according to the progression of the disease[5,6,7,8]. Few studies have focused on the mass effect resulting from a haematoma in primary brain injury[2,15]. The blood model mimics a single large bleed that occurs in most ICH patients, and the bacterial collagenase injection can disrupt the basal lamina of cerebral blood vessels and cause the blood to leak into the surrounding brain tissue[17]. The common ICH animal models cannot effectively avoid the secondary brain insults caused by the physiological response to the haematoma (e.g., inflammation) and the release of clot components (e.g. haemoglobin and iron)[1]. The PNIPAM hydrogel has the potential to establish an ICH model for mechanical damage research. The aim of the present study was to establish a rodent ICH model using injectable thermo-sensitive hydrogel to study the mass effect damage caused by ICH. The establishment of a mass effect ICH model helps elucidate the mechanism of primary brain injury after ICH, which could be used to investigate the role of mass effect in secondary brain damage after ICH
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