Optimized mouse model of embolic MCAO: From cerebral blood flow to neurological outcomes

2020 ◽  
pp. 0271678X2091762 ◽  
Author(s):  
Rongrong Wang ◽  
Hailian Wang ◽  
Yaan Liu ◽  
Di Chen ◽  
Yangfan Wang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Mouse Model ◽  
Infarct Volume ◽  
Laser Speckle ◽  
Core Area ◽  
Contrast Imaging ◽  
Vessel Occlusion ◽  
Doppler Flowmetry

The embolic middle cerebral artery occlusion (eMCAO) model mimics ischemic stroke due to large vessel occlusion in humans and is amenable to thrombolytic therapy with rtPA. However, two major obstacles, the difficulty of the eMCAO surgery and unpredictable occurrence of clot autolysis, had impeded its application in mice. In this study, we modified catheters to produce suitable fibrin-rich embolus and optimized the eMCAO model using cerebral blood flow (CBF) monitored by both laser Doppler flowmetry (LDF) and 2D laser speckle contrast imaging (LSCI) to confirm occlusion of MCA. The results showed that longer embolus resulted in higher mortality. There was a compensatory increase in MCA territory perfusion after eMCAO associated with decreased infarct volume; however, this was only partly dependent on recanalization as clot autolysis was only observed in ∼30% of mice. Cortical CBF monitoring with LSCI showed that the size of peri-core area at 3 h displayed the best correlation with infarct volume that is attributed to compensatory collateral blood flow. The peri-core area best predicted functional outcome after eMCAO. In summary, we developed a reliable eMCAO mouse model that better mimics embolic ischemic stroke in humans, which will increase the potential for successful translation of stroke neuroprotective therapies.

scholarly journals Laser Speckle Contrast Imaging of Collateral Blood Flow during Acute Ischemic Stroke

2010 ◽  
Vol 30 (8) ◽  
pp. 1432-1436 ◽  
Author(s):  
Glenn A Armitage ◽  
Kathryn G Todd ◽  
Ashfaq Shuaib ◽  
Ian R Winship
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Cerebral Arteries ◽  
Artery Occlusion ◽  
Laser Speckle ◽  
Collateral Blood Flow ◽  
Contrast Imaging ◽  
Vessel Occlusion ◽  
Laser Speckle Contrast Imaging ◽  
Speckle Contrast

Collateral vasculature may provide an alternative route for blood flow to reach the ischemic tissue and partially maintain oxygen and nutrient support during ischemic stroke. However, much about the dynamics of stroke-induced collateralization remains unknown. In this study, we used laser speckle contrast imaging to map dynamic changes in collateral blood flow after middle cerebral artery occlusion in rats. We identified extensive anastomatic connections between the anterior and middle cerebral arteries that develop after vessel occlusion and persist for 24 hours. Augmenting blood flow through these persistent yet dynamic anastomatic connections may be an important but relatively unexplored avenue in stroke therapy.

scholarly journals Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1161
Author(s):  
Chenghui Ye ◽  
Yubin Liang ◽  
Ying Chen ◽  
Yu Xiong ◽  
Yingfang She ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Mouse Model ◽  
Laser Speckle ◽  
Cerebral Hypoperfusion ◽  
Contrast Imaging ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

Alzheimer’s disease (AD) is accompanied by β-amyloid (Aβ), neurofibrillary tangles, and neuron cell death, and is one of the most commonly occurring diseases among the elderly. The pathology of AD is complex, involving Aβ overproduction and accumulation, tau hyperphosphorylation, and neuronal loss. In addition, chronic cerebral hypoperfusion (CCH) is ubiquitous in the AD patients and plans a pivotal role in triggering and exacerbating the pathophysiological progress of AD. The goal of this study was to investigate the neuroprotective properties of berberine (BBR) and the underlying mechanism. During the study, BBR was administrated to treat the triple-transgenic mouse model of Alzheimer’s disease (3×Tg AD). To thoroughly evaluate the effects of the BBR administration, multiple manners were utilized, for instance, 3D arterial spin labeling technique, Morris water maze assay, immunofluorescence staining, TUNEL assay, laser speckle contrast imaging, western blotting, etc. The results showed that BBR ameliorated cognitive deficits in 3×Tg AD mice, reduced the Aβ accumulation, inhibited the apoptosis of neurons, promoted the formation of microvessels in the mouse brain by enhancing brain CD31, VEGF, N-cadherin, Ang-1. The new vessels promoted by BBR were observed to have a complete structure and perfect function, which in turn promoted the recovery of cerebral blood flow (CBF). In general, berberine is effective to 3×Tg AD mice, has a neuroprotective effect, and is a candidate drug for the multi-target prevention and treatment of AD.

scholarly journals Modern Diagnostic Techniques for the Assessment of Ocular Blood Flow in Myopia: Current State of Knowledge

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ewa Grudzińska ◽  
Monika Modrzejewska
Keyword(s):  
Blood Flow ◽  
Optical Coherence Tomography ◽  
Refractive Error ◽  
Retinal Vessel ◽  
Ocular Blood Flow ◽  
Laser Speckle ◽  
Doppler Imaging ◽  
Optical Coherence ◽  
Contrast Imaging ◽  
Doppler Flowmetry

Myopia is the most common refractive error and the subject of interest of various studies assessing ocular blood flow. Increasing refractive error and axial elongation of the eye result in the stretching and thinning of the scleral, choroid, and retinal tissues and the decrease in retinal vessel diameter, disturbing ocular blood flow. Local and systemic factors known to change ocular blood flow include glaucoma, medications and fluctuations in intraocular pressure, and metabolic parameters. Techniques and tools assessing ocular blood flow include, among others, laser Doppler flowmetry (LDF), retinal function imager (RFI), laser speckle contrast imaging (LSCI), magnetic resonance imaging (MRI), optical coherence tomography angiography (OCTA), pulsatile ocular blood flowmeter (POBF), fundus pulsation amplitude (FPA), colour Doppler imaging (CDI), and Doppler optical coherence tomography (DOCT). Many researchers consistently reported lower blood flow parameters in myopic eyes regardless of the used diagnostic method. It is unclear whether this is a primary change that causes secondary thinning of ocular tissues or quite the opposite; that is, the mechanical stretching of the eye wall reduces its thickness and causes a secondary lower demand of tissues for oxygen. This paper presents a review of studies assessing ocular blood flow in myopes.

scholarly journals Computed Tomography Perfusion–Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 223-231
Author(s):  
Hulin Kuang ◽  
Wu Qiu ◽  
Anna M. Boers ◽  
Scott Brown ◽  
Keith Muir ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Interquartile Range ◽  
Time Dependent ◽  
Computed Tomography Perfusion

Background and Purpose: Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion–based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke. Methods: Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model. Average map, T max , cerebral blood flow, cerebral blood volume, and time variables including stroke onset-to-imaging and imaging-to-reperfusion time, were used as features to train the ML model. Spatial and volumetric agreement between the ML model predicted follow-up infarct and actual follow-up infarct were assessed. Relative cerebral blood flow <0.3 threshold using RAPID software and time-dependent T max thresholds were compared with the ML model. Results: In the test cohort (137 patients), median follow-up infarct volume predicted by the ML model was 30.9 mL (interquartile range, 16.4–54.3 mL), compared with a median 29.6 mL (interquartile range, 11.1–70.9 mL) of actual follow-up infarct volume. The Pearson correlation coefficient between 2 measurements was 0.80 (95% CI, 0.74–0.86, P <0.001) while the volumetric difference was −3.2 mL (interquartile range, −16.7 to 6.1 mL). Volumetric difference with the ML model was smaller versus the relative cerebral blood flow <0.3 threshold and the time-dependent T max threshold ( P <0.001). Conclusions: A ML using computed tomography perfusion data and time estimates follow-up infarction in patients with acute ischemic stroke better than current methods.

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