Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice

Abstract

In this study, we examined injury progression after intracerebral haemorrhage (ICH) induced by collagenase in mice using a preclinical 11.7 Tesla MRI system. On T2-weighted MRI, lesion and striatal volumes were increased on day 3 and then decreased from days 7 to 28. On day 3, with an increase in striatal water content, vasogenic oedema in the perihaematomal region presented as increased T2 and increased apparent diffusion coefficient (ADC) signal. With a synchronous change in T2 and ADC signals, microglial activation peaked on day 3 in the same region and decreased over time. Iron deposition appeared on day 3 around the haematoma border but did not change synchronously with ADC signals. Vascular permeability measured by Evans blue extravasation on days 1, 3, and 7 correlated with the T1-gadolinium results, both of which peaked on day 3. On diffusion tensor imaging, white matter injury was prominent in the corpus callosum and internal capsule on day 3 and then partially recovered over time. Our results indicate that the evolution of grey/white matter injury and blood-brain barrier disruption after ICH can be assessed with multimodal MRI, and that perihaematomal vasogenic oedema might be attributable to microglial activation, iron deposition, and blood-brain barrier breakdown.

Intracerebral haemorrhage-induced injury progression assessed by cross-sectional photoacoustic tomography

“…On day 28, oxy-HVR and deoxy-HVR in haemorrhagic area came to the normal level. These process was also observed by MRI in previous studies [3,40]. Quantitative analysis showed timedependent changes in ratio of oxy-HVR in main lesion area and perihemmatoma indicated by blue dashed line shown in the first image of Figs.…”

“…Clinically, ICH is caused by rupture of a tiny artery, which leads to formation of a haematoma or blood clot in the lesion core, with tissues pressed and distorted in the periphery [3,36]. At the beginning, with the rupture of a tiny artery, the main hemoglobin formation was HbO 2 in the lesion core [35].…”

“…ICH model was induced by injecting collagenase into the right striatum (caudate putamen, CPu) of a mouse according to a well established method [3,26]. A burr hole was drilled into the skull, and type VII-S collagenase (0.075 U in 0.5μl saline; Sigma, St. Louis, MO) was infused into the right striatum with a micro-infusion pump at a constant rate of 0.1 μl/min.…”

“…On days 1, 3, 7, and 28 after surgery, an investigator blinded to the group assignment evaluated the mice functional deficits by an NDS(Neurologic deficit score) system that includes six domains of body symmetry, gait, climbing, circling behavior, front limb symmetry, and compulsory circling as described in previous studies [3,29]. Each test was graded from 0 to 4, providing a total score of 0 to 24, with higher scores indicative of greater neurologic injury [29,31,32].…”

“…Yet, interventions for ICH are still very limited [3]. So understanding the mechanisms of ICH pathology and repair, and identifying potential treatments have high priorities.…”