Spatiotemporal characterization of brain infarction by sequential multimodal MR imaging following transient focal ischemia in a Rat model of intra-arterial middle cerebral artery occlusion.

OBJECTIVES: To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. MATERIALS AND METHODS: A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90 minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3 h and 24 h after subsequent reperfusion. RESULTS: MCA occlusion was complete in 75 % and partial in 18.7 %. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18 % of contralateral hemisphere, area 31 ± 5 mm2). Infarction volume (mean ± SD) was 90 ± 64 mm3 during ischemia and 57 ± 67 mm3 at 24 h. Brain infarction was fronto-parietal cortical in five animals (31 %), striatal in four animals (25 %), and cortico-striatal in seven animals (44 %) at 24 h. All rats survived at 24 h. CONCLUSION: This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. KEY POINTS: • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

Outcomes of stent retriever thrombectomy in basilar artery occlusion: an observational study and systematic review.

BACKGROUND: Basilar artery occlusion (BAO) remains one of the most devastating subtypes of stroke with high mortality and poor outcome. Early recanalisation is the most powerful predictor of favourable outcome in patients with stroke, and may be improved with mechanical thrombectomy using stent retriever devices. However, the benefit in functional outcome and safety of stent retrievers are not yet well known. The aim of this study was to assess efficacy and safety profiles of stent retriever thrombectomy in BAO patients with stroke. METHODS: We analysed data retrospectively from our consecutive clinical series and conducted a systematic review and meta-analysis of all previous studies of stent retriever thrombectomy in BAO patients with stroke between November 2010 and April 2014. RESULTS: From March 2010 to March 2013, 22 patients with acute BAO were treated with a Solitaire stent retriever in our series. Favourable outcome was significantly associated with younger age and distal BAO. The literature search identified 15 previous studies involving a total of 312 subjects. In the meta-analysis, including our series data, the recanalisation rate (Thrombolysis In Cerebral Infarction (TICI) score ≥ 2b) reached 81% (95% CI 73% to 87%). The rate of symptomatic intracranial haemorrhage was 4% (95% CI 2% to 8%), favourable outcome (modified Rankin Scale (mRS) ≤ 2 at 3 months) was found in 42% (95% CI 36% to 48%) and mortality rate was 30% (95% CI 25% to 36%). CONCLUSIONS: Stent retriever thrombectomy is a safe treatment modality for patients with stroke presenting with BAO. Although the stent retrievers showed a good recanalisation rate, there are currently no randomised clinical trials to assess its clinical efficacy in comparison with the reference treatment.

Endothelial cell-specific expression of roundabout 4 is regulated by differential DNA methylation of the proximal promoter.

OBJECTIVE: The molecular basis of endothelial cell (EC)-specific gene expression is poorly understood. Roundabout 4 (Robo4) is expressed exclusively in ECs. We previously reported that the 3-kb 5'-flanking region of the human Robo4 gene contains information for lineage-specific expression in the ECs. Our studies implicated a critical role for GA-binding protein and specificity protein 1 (SP1) in mediating overall expression levels. However, these transcription factors are also expressed in non-ECs. In this study, we tested the hypothesis that epigenetic mechanisms contribute to EC-specific Robo4 gene expression. METHODS AND RESULTS: Bisulfite sequencing analysis indicated that the proximal promoter of Robo4 is methylated in non-ECs but not in ECs. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine increased Robo4 gene expression in non-ECs but not in ECs. Proximal promoter methylation significantly decreased the promoter activity in ECs. Electrophoretic mobility shift assays showed that DNA methylation of the proximal promoter inhibited SP1 binding to the -42 SP1 site. In DNase hypersensitivity assays, chromatin condensation of the Robo4 promoter was observed in some but not all nonexpressing cell types. In Hprt (hypoxanthine phosphoribosyltransferase)-targeted mice, a 0.3-kb proximal promoter directed cell-type-specific expression in the endothelium. Bisulfite sequencing analysis using embryonic stem cell-derived mesodermal cells and ECs indicated that the EC-specific methylation pattern of the promoter is determined by demethylation during differentiation and that binding of GA-binding protein and SP1 to the proximal promoter is not essential for demethylation. CONCLUSIONS: The EC-specific DNA methylation pattern of the Robo4 proximal promoter is determined during cell differentiation and contributes to regulation of EC-specific Robo4 gene expression.