Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model

Background Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. Methods In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. Results The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1β, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. Conclusions These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.

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A canine model of mechanical thrombectomy in stroke

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2019-014969 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1243-1248 ◽

Cited By ~ 4

Author(s):

Olivia W Brooks ◽

Robert M King ◽

Erez Nossek ◽

Miklos Marosfoi ◽

Jildaz Caroff ◽

...

Keyword(s):

Mechanical Thrombectomy ◽

Infarct Volume ◽

Canine Model ◽

Preclinical Model ◽

Large Animal ◽

Stroke Model ◽

Vessel Occlusion ◽

Stroke Treatment ◽

Iatrogenic Trauma ◽

And Diffusion

PurposeTo develop a preclinical model of stroke with a large vessel occlusion treated with mechanical thrombectomy.Materials and methodsAn ischemic stroke model was created in dogs by the introduction of an autologous clot into the middle cerebral artery (MCA). A microcatheter was navigated to the clot and a stent retriever thrombectomy was performed with the goal to achieve Thrombolysis in Cerebral Ischemia (TICI) 2b/3 reperfusion. Perfusion and diffusion MRI was acquired after clot placement and following thrombectomy to monitor the progression of restricted diffusion as well as changes in ischemia as a result of mechanical thrombectomy. Post-mortem histology was done to confirm MCA territory infarct volume.ResultsInitial MCA occlusion with TICI 0 flow was documented in all six hound-cross dogs entered into the study. TICI 2b/3 revascularization was achieved with one thrombectomy pass in four of six animals (67%). Intra-procedural events including clot autolysis leading to spontaneous revascularization (n=1) and unresolved vasospasm (n=1) accounted for thrombectomy failure. In one case, iatrogenic trauma during microcatheter navigation resulted in a direct arteriovenous fistula at the level of the cavernous carotid. Analysis of MRI indicated that a volume of tissue from the initial perfusion deficit was spared with reperfusion following thrombectomy, and there was also a volume of tissue that infarcted between MRI and ultimate recanalization.ConclusionWe describe a large animal stroke model in which mechanical thrombectomy can be performed. This model may facilitate, in a preclinical setting, optimization of complex multimodal stroke treatment paradigms for clinical translation.

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