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Surgical set up of the permanent distal middle cerebral artery occlusion model. The equipment used in the set up for the rat craniotomy is shown for the right hemisphere, and inset, the positioning of the aspirator and saline drip around the craniectomy site. Also shown are the key features of the vasculature; the middle cerebral artery (red) and inferior cerebral vein (blue) are shown, and the shaded area indicates where coagulation of the artery occurs. Confirmation of the occlusion is performed by cutting the MCA below the inferior cerebral vein. Please click here to view a larger version of this figure.  

Surgical set up of the permanent distal middle cerebral artery occlusion model. The equipment used in the set up for the rat craniotomy is shown for the right hemisphere, and inset, the positioning of the aspirator and saline drip around the craniectomy site. Also shown are the key features of the vasculature; the middle cerebral artery (red) and inferior cerebral vein (blue) are shown, and the shaded area indicates where coagulation of the artery occurs. Confirmation of the occlusion is performed by cutting the MCA below the inferior cerebral vein. Please click here to view a larger version of this figure.  

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Article
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Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, obesity and diabetes. Accordingly, when evaluating therapies for stroke in animals, it is important to select a model with excellent face validity. Ischemic stroke accounts for 80% of all strokes, and t...

Contexts in source publication

Context 1
... a homemade dural hook, made by bending one tip of fine forceps approximately 180° to form an arc, to carefully open the dura, being cautious to avoid the large surface blood vessels, as they are delicate and easy to rupture. Note: The exposed area of the brain will reveal the middle cerebral artery (MCA); the desired segment measures approximately 2 mm in length (see Figure 1, inset). 15. ...
Context 2
... MCAO was induced by performing craniotomy, followed by coagulation and destruction of the middle cerebral artery by diathermy combined with permanent occlusion of the ipsilesional common carotid artery and 60 min occlusion of the contralesional common carotid artery. A schematic of the setup of the equipment and occluded MCA is shown in Figure 1, and of the carotid arteries in Figure 2 (above). ...

Citations

... Among these methods, craniotomy is a common method, that has the advantage of allowing direct visualization of MCA through the surgical field (9). After the MCA has been exposed, it can be occluded by coagulation, transection, ligation or clips (7). ...
Article
Background/aim: Middle cerebral artery occlusion (MCAO) in rodents is an essential animal model for research focusing on ischemic stroke. To date, several kinds of surgical methods for MCAO have been developed and the craniotomy method has the advantage of direct visualization of the middle cerebral artery (MCA). MCAO at a more proximal site produces better surgical results, but it is a more invasive technique. The aim of this study was to evolve the surgical technique for simulating ischemic cerebral cortex injury in rats. Materials and methods: To approach proximal MCA with a less invasive procedure, a modified surgical technique for MCAO in rats was developed. Besides, rats receiving the modified and conventional method were compared with regard to infarct volume and by behavioral tests. Results: Following craniotomy, we proposed that the inferior edge of the craniotomy should be enlarged with fine forceps. This modified surgical method induces larger infarct volume, significant behavioral impairment and can induce ischemic stroke. Additionally, it does not significantly increase the operation time, and has produced no obvious complications. Conclusion: This modified surgical technique may serve as a practical method for performing MCAO.
... The aged brain displays a higher susceptibility to hypoxia compared with young animals in the acute phase of stroke [25,26]. On MRI images, aged ischemic rats displayed more severe lesions, which had similar localizations, but higher incidence and more rapid appearance than in the young rats [22,23,27,28]. With the use of functional Magnetic Resonance Imaging (fMRI), it was demonstrated that patterns of bihemispheric reorganization (increase of the fMRI response in the ipsilateral somatosensory cortex and bilateral thalamic activation) after permanent middle cerebral artery occlusion (MCAO) in aged rats, were the same as in young animals, although the overall time course of recovery in aged rats was more prolonged than that in young rats [24,29]. ...
Article
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The aging process, comorbidities, and age-associated diseases are closely dependent on each other. Cerebral ischemia impacts a wide range of systems in an age-dependent manner. However, the aging process has many facets which are influenced by the genetic background and epigenetic or environmental factors, which can explain why some people age differently than others. Therefore, there is an urgent need to identify age-related changes in body functions or structures that increase the risk for stroke and which are associated with a poor outcome. Multimodal imaging, electrophysiology, cell biology, proteomics, and transcriptomics, offer a useful approach to link structural and functional changes in the aging brain, with or without comorbidities, to post-stroke rehabilitation. This can help us to improve our knowledge about senescence firstly, and in this context, aids in elucidating the pathophysiology of age-related diseases that allows us to develop therapeutic strategies or prevent diseases. These processes, including potential therapeutical interventions, need to be studied first in relevant preclinical models using aged animals, with and without comorbidities. Therefore, preclinical research on ischemic stroke should consider age as the most important risk factor for cerebral ischemia. Furthermore, the identification of effective therapeutic strategies, corroborated with successful translational studies, will have a dramatic impact on the lives of millions of people with cerebrovascular diseases.
... It is considered good practice to provide aged animals with chew blocks and to regularly check their teeth. If overgrown teeth are identified they can be trimmed, under brief general anaesthesia, using a rotary dental disk cutter (for video see Wayman et al. 79 ). If overgrown teeth are identified then it is likely that they will require fairly frequent treatment (e.g. ...
... 175 To generate more consistent infarcts, permanent distal MCA occlusion can be combined with tandem CCA occlusion in rats. 79 Surgeons should start with a short CCA occlusion time (e.g. 30 min) to see whether adequate lesion volumes (and/or required behavioural deficits) are obtained and only then increase CCA occlusion if necessary. Anecdotally, higher mortality is found in elderly male rather than elderly female rats with equivalent occlusion times so shorter occlusion times may be required for elderly males. ...
Article
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Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information).
... Following the induction of anesthesia (see above), the left CCA was dissected as reported in the literature ( Wayman et al., 2016), before proceeding to the above-described craniotomies (Figure 9- 6-A). Two loose knots were placed around the CCA. ...
Thesis
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Since the middle of the 20th century, functional imaging technologies are making an increasing impact on our understanding on brain functions in both physiological and pathological conditions. Even if fMRI is nowadays one of the most used tool for whole brain imaging in pre-clinical and clinical studies, it lacks sufficient spatiotemporal resolution and sensitivity to assess fine brain function and activity. Functional ultrasound imaging (fUSi) has been recently developed and presents a potential to complement fMRI and other existing brain imaging modalities. Contrary to conventional ultrasound using focus beams, fUSi relies on hemodynamic imaging based on ultrasound plane-wave illumination to detect red blood cells movement and velocity in brain micro-vessels. Consequently, the fUSi signal is indirectly related to brain activity and it is therefore important to better understand the mechanisms of the neurovascular coupling linking neural activity and cerebral blood changes. Here again, fUSi may provide relevant information about disease processes in preclinical models but also in humans. First, I will present recent technical developments allowing in vivo fUSi (i) in chronic condition, (ii) in freely moving and behaving rats and (iii) in rodents and human brain capillaries. Second, I will demonstrate how fUSi could provide new insights in brain pathologies such as stroke.
Preprint
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Ischemic stroke occurs with no warning, and therefore, very little is known about hemodynamic perturbations in the brain immediately after stroke onset. In this study, functional ultrasound imaging was used to monitor the hemodynamic changes in relative cerebral blood volume (rCBV) compared to baseline. rCBV variations were analyzed brain-wide and continuously at high spatiotemporal resolution (100μm, 2Hz) until 70mins after stroke onset in rats. We compared two stroke models, with either a permanent occlusion of the middle cerebral artery (MCAo) or a tandem occlusion of both the common carotid and middle cerebral arteries (CCAo+MCAo). We observed a typical hemodynamic pattern, including a quick drop of the rCBV after MCAo, followed by spontaneous reperfusion of several brain regions located in the vicinity of the ischemic core. The severity and location of the ischemia were highly variable between animals. Still, both parameters were, on average, in good agreement with the final ischemic lesion volume measured 24hrs after stroke onset for the MCAo but not the CCAo+MCAo model. For the latter, we observed that the infarct was extended to regions that were initially not ischemic and located rostrally of the ischemic core. These regions strongly colocalize with the origin of transient hemodynamic events associated with spreading depolarizations.
Article
FAILLOT, M., A. CHAILLET, S. PALFI and S. SENOVA. Rodent models used in preclinical studies of deep brain stimulation to rescue memory deficits…NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, YEAR.- Deep brain stimulation paradigms might be used to treat memory disorders in patients with stroke or traumatic brain injury. However, proof of concept studies in animal models are needed before clinical translation. We propose here a comprehensive review of rodent models for Traumatic Brain Injury and Stroke. We systematically review the histological, behavioral and electrophysiological features of each model and identify those that are the most relevant for translational research.
Article
Magnetic resonance imaging (MRI) paradigms, using non-invasive approaches, can provide relevant findings about brain aging. The attention has been primarily focused on neurodegenerative diseases, while little or nothing has been done to differentiate physiology from pathology. The present study aimed to test diffusion tensor imaging (DTI) and functional MRI (fMRI) metrics to analyze physiological age-related changes in rats at myelin structure and activation level; findings were validated by ex vivo histology. The purpose is to find comparable biomarkers in rodents and humans to allow a reliable translation from pre-clinical to clinical settings. Data evidenced: i) a significantly higher cerebrospinal fluid volume in middle-aged and aged vs. young rats; ii) a progressive alteration of white matter; iii) a significant reduction of evoked activity in aged animals. These results partially mirror the age-related changes in humans and may represent a preliminary step to find reliable tools for a lifelong monitoring with a value for the clinical practice (e.g., to provide support to the early diagnosis of dementia in asymptomatic subjects).
Preprint
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There is an urgent need for a therapy which reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. Neurotrophin-3 (NT3) is a growth factor made by muscle spindles and skin which is required for the survival, development and function of locomotor circuits involving afferents from muscle and skin that mediate proprioception and tactile sensation. We set out to determine whether subcutaneous supplementation of NT3 improves sensorimotor recovery after stroke in elderly rats. We show that one-month-long subcutaneous infusion of NT3 protein induces sensorimotor recovery after cortical stroke in elderly rats. Specifically, in a randomised, blinded pre-clinical trial, we show improved dexterity, walking and sensory function in rats following cortical ischemic stroke when treatment with NT3 is initiated 24 hours after stroke. Importantly, NT-3 was given in a clinically-feasible timeframe via this straightforward route. MRI and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, anterograde tracing showed that corticospinal axons from the less-affected hemisphere sprouted in the spinal cord from cervical levels 2 to 8. Importantly, Phase I and II clinical trials by others show that repeated, subcutaneously administered high doses of recombinant NT-3 are safe and well tolerated in humans with other conditions. This paves the way for NT-3 as a therapy for stroke.
Chapter
Developing reliable and reproducible animal model is of great importance in the therapeutic research of ischemic stroke. The location and volume of injury are varied in different animal models. Researchers choose different animal models according to the research purposes. In this chapter, we summarized the system of ischemic stroke models.