Animal Models of Focal Cerebral Ischaemia and Haemorrhagic Transformation: Considerations in Experimental Stroke Study Design

Shearer, Jennifer A.; Douglas, Andrew; Kirby, Brian P.; Tatlısumak, Turgut; Doyle, Karen M.

doi:10.2174/1570161115666170906115300

Cited by 2 publications

(1 citation statement)

References 143 publications

(240 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The intraluminal thread model used to cause MCAo is relatively non-invasive and results in a large infarct localised to striatal regions, particularly basal ganglia and cortex; it is typically considered as a clinically relevant model of large vessel occlusion 20 . At 24 h after 30 min transient MCAo, median Bederson score was 3 and mean lesion volume was 42.3mm 3 , consistent with a recent report that documented Bederson scores of 3-5 and mean lesion volume of 77.5mm 3 after 45 min of MCAo 21 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel model of global forebrain ischaemia–reperfusion injury in mice and comparison with focal ischaemic and haemorrhagic stroke

Lee

Selan

Chia

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Stroke is caused by obstructed blood flow (ischaemia) or unrestricted bleeding in the brain (haemorrhage). Global brain ischaemia occurs after restricted cerebral blood flow e.g. during cardiac arrest. Following ischaemic injury, restoration of blood flow causes ischaemia–reperfusion (I/R) injury which worsens outcome. Secondary injury mechanisms after any stroke are similar, and encompass inflammation, endothelial dysfunction, blood–brain barrier (BBB) damage and apoptosis. We developed a new model of transient global forebrain I/R injury (dual carotid artery ligation; DCAL) and compared the manifestations of this injury with those in a conventional I/R injury model (middle-cerebral artery occlusion; MCAo) and with intracerebral haemorrhage (ICH; collagenase model). MRI revealed that DCAL produced smaller bilateral lesions predominantly localised to the striatum, whereas MCAo produced larger focal corticostriatal lesions. After global forebrain ischaemia mice had worse overall neurological scores, although quantitative locomotor assessment showed MCAo and ICH had significantly worsened mobility. BBB breakdown was highest in the DCAL model while apoptotic activity was highest after ICH. VCAM-1 upregulation was specific to ischaemic models only. Differential transcriptional upregulation of pro-inflammatory chemokines and cytokines and TLRs was seen in the three models. Our findings offer a unique insight into the similarities and differences in how biological processes are regulated after different types of stroke. They also establish a platform for analysis of therapies such as endothelial protective and anti-inflammatory agents that can be applied to all types of stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of a novel model of global forebrain ischaemia–reperfusion injury in mice and comparison with focal ischaemic and haemorrhagic stroke

Lee

Selan

Chia

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice or innocent bystander?

Ouk

Potey

Maestrini

et al. 2019

Pharmacology & Therapeutics

View full text Add to dashboard Cite

The risk of intracerebral hemorrhage still greatly limits the use of tPA in stroke patients. Research is ongoing in order to identify the pathophysiological mechanisms at play, detect predictive biomarkers and discover new pharmacological targets to develop preventive or curative treatments. Going through experimental and clinical studies, this review focuses on the role of neutrophils as key predictive biomarkers for thrombolysis-induced hemorrhages and as pharmacological targets to limit their occurrence. To date, there are no established pharmacological modulators of neutrophils for ischemic stroke and its hemorrhagic complications. Several strategies are under evaluation, including lipid-lowering drugs, free radical scavengers, or minocycline, as well as non-pharmacological interventions such as physical exercise.

show abstract

Animal Models of Focal Cerebral Ischaemia and Haemorrhagic Transformation: Considerations in Experimental Stroke Study Design

Abstract: A number of factors can be added to the animal model design to increase the incidence and/or severity of haemorrhagic transformation post-ischaemic stroke, which can improve clinical relevance, aid the study of the pathophysiology and the future development of novel interventions.

Cited by 2 publications

References 143 publications

Characterization of a novel model of global forebrain ischaemia–reperfusion injury in mice and comparison with focal ischaemic and haemorrhagic stroke

Characterization of a novel model of global forebrain ischaemia–reperfusion injury in mice and comparison with focal ischaemic and haemorrhagic stroke

Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice or innocent bystander?

Contact Info

Product

Resources

About