scholarly journals A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

2020 ◽  
pp. 0271678X2092131 ◽  
Author(s):  
Justine Debatisse ◽  
Océane Wateau ◽  
Tae-Hee Cho ◽  
Nicolas Costes ◽  
Inés Mérida ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Fine Motor ◽  
Area At Risk ◽  
Primate Model ◽  
Endovascular Thrombectomy ◽  
Blood Brain Barrier Disruption ◽  
Reperfusion Damage ◽  
Brain Barrier Disruption ◽  
Human Primate

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood–brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia ( Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: “symptomatic salvaged tissue” (SST) and “asymptomatic infarcted tissue” (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia–reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

scholarly journals Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bailey Hiles-Murison ◽  
Andrew P. Lavender ◽  
Mark J. Hackett ◽  
Joshua J. Armstrong ◽  
Michael Nesbit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Hippocampal Formation ◽  
Brain Barrier ◽  
Lateral Ventricles ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Underlying Mechanisms

AbstractRepeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.

scholarly journals Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status

2020 ◽  
Vol 40 (7) ◽  
pp. 1415-1426 ◽  
Author(s):  
Di Wu ◽  
Jian Chen ◽  
Mohammed Hussain ◽  
Longfei Wu ◽  
Jingfei Shi ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Motor Dysfunction ◽  
Neurological Deficits ◽  
Brain Cooling ◽  
Long Term Outcomes ◽  
Primate Model ◽  
Tissue Plasminogen ◽  
Human Primate ◽  
Arterial Thrombolysis

Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes – complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.

Nomilin protects against cerebral ischemia–reperfusion induced neurological deficits and blood–brain barrier disruption via the Nrf2 pathway

2019 ◽  
Vol 10 (9) ◽  
pp. 5323-5332 ◽  
Author(s):  
Yu-Sheng Shi ◽  
Yan Zhang ◽  
Bin Liu ◽  
Chun-Bin Li ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Nrf2 Pathway ◽  
Blood Brain Barrier Disruption ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Brain Barrier Disruption

Oxidative stress is considered to play an important role in the cerebral ischemia–reperfusion injury.

Kudiezi Injection®Alleviates Blood-Brain Barrier Disruption After Ischemia-Reperfusion in Rats

2016 ◽  
Vol 23 (6) ◽  
pp. 426-437 ◽  
Author(s):  
Fu-Qin Chen ◽  
Quan Li ◽  
Chun-Shui Pan ◽  
Yu-Ying Liu ◽  
Li Yan ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption
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