Method parameters’ impact on mortality and variability in rat stroke experiments: a meta-analysis

Ström, Jakob O.; Ingberg, Edvin; Theodorsson, Annette; Theodorsson, Elvar

doi:10.1186/1471-2202-14-41

Cited by 52 publications

(63 citation statements)

References 374 publications

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“…Our success rate of inducing an infarction by a 90-minute middle cerebral artery occlusion was 90 % (only one animal had no ischemic lesions according to the MRI examination), in accordance with another report (Bacigaluppi, tomi & Hermann, 2010). With reference to the animal models, the infarction size reportedly is dependent on rat strains: the Wistar strain and the intraluminal filament procedure, using a silicone-coated filament, gives the lowest variability (Strom et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Horváth

Orădan

Chiriac

et al. 2018

Preprint

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Background and Objective:Clinical and experimental observations emphasize the role of inflammation as a direct risk factor for stroke. To better characterize the inflammation, we have conducted a detailed histological analysis of the inflammatory cell population after transient middle cerebral artery occlusion in a rat model. Methods:Fifteen adult Wistar male rats were divided randomly into test (n=10) and sham (n=5) groups. In the ischemic group, transient focal cerebral ischemia was induced with an intraluminal filament technique. Histologic lesions of the ischemic core and the surrounding penumbra zone were evaluated, based on a complex algorithm. Representative morphological changes in the core and the penumbra zone were compared. Immunohistochemistry was performed for leukocytes markers (CD15, CD68, CD3), leukocyte-released effectors (MMP-9 and COX-2), and FXIII (possibly involved in microglia and macrophage activation)Results: Neuronal vacuolation and degeneration were significantly more in the core lesion, whereas cellular edema and inflammatory infiltrate were increased in the penumbra. CD68, CD3, FXIII and Cox-2 expression were significantly higher in the penumbra than in the core (p=0.026; p=0.006; p=0.002; and p<0.001).Discussion: In the rat model of middle cerebral artery occlusion, inflammatory mechanisms, microglia/macrophage cells, and T-lymphocytes likely play an important role in the penumbra. The deterioration of neurons is less in the penumbra than in the core. Appreciation of the role of the inflammatory cells and mechanisms involved in stroke might lead to measures to inhibit the injury and save brain volume. ABSTRACT Background and Objective: Clinical and experimental observations emphasize the role of inflammation as a direct risk factor for stroke. To better characterize the inflammation, we have conducted a detailed histological analysis of the inflammatory cell population after transient middle cerebral artery occlusion in a rat model.

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Section: Discussionmentioning

confidence: 99%

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Horváth

Orădan

Chiriac

et al. 2018

Preprint

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“…The mouse strain in Paper I, C57BL6, is the most widely used inbred strain (https://www.jax.org/strain/000664, accessed 2015-10-05) and was therefore considered suitable for a study with the goal of establishing a protocol for other researchers to adopt in their experiments. For Paper IV outbred albino Wistar rats were used, and this strain is very common in rat stroke experiments (second only to Sprague Dawley among the 304 studies included in Paper II [133]). We have previously worked with Sprague Dawley rats (another outbred albino strain) in our lab but switched to Wistar in an effort to try to reduce infarct size variability [133,134].…”

Section: Animalsmentioning

confidence: 99%

“…For Paper IV outbred albino Wistar rats were used, and this strain is very common in rat stroke experiments (second only to Sprague Dawley among the 304 studies included in Paper II [133]). We have previously worked with Sprague Dawley rats (another outbred albino strain) in our lab but switched to Wistar in an effort to try to reduce infarct size variability [133,134]. Both Papers I and IV have a bearing on the clinical issue of hormone replacement therapy for menopausal women, why female animal models were considered more relevant.…”

Section: Animalsmentioning

confidence: 99%

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Challenges in experimental stroke research : The 17β-estradiol example

Ingberg¹

2016

Linköping University Medical Dissertations

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“…By working on data from 502 control groups described in 346 articles, Ström et al have investigated the method parameters' impact on mortality and variability. Their metaanalysis has revealed that the Wistar strain and intraluminal filament procedure using a silicone-coated filament resulted in smallest infarct size variability (36).…”

Section: █ Discrepanciesmentioning

confidence: 99%

Searching evidences of stroke in animal models: a review of discrepancies

Kaya

Erdoğan²,

Taşdemiroğlu³

2016

Turkish Neurosurgery

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ABSTRACTcan be replaced with ketone bodies. In total starvation such as global cerebral ischemia, the brain's limited reserves of glycogen and glucose are barely able to fuel normal brain activity up to 5 minutes. It is reported that the energy stores of the brain are equivalent to 20 cl/100 gr (39). In a healthy person, cerebral blood flow (CBF) is autoregulated at 45-50 ml/100gr/min with a mean arterial blood pressure (MABP) of 60-130 mm/Hg (Figure 1). In the cerebral ischemia model, the investigators try to reduce the oxygen and glucose supply of cerebral tissue. This process produces ischemic brain injury via a variety of cellular and molecular mechanisms.There are three major types of ischemic stroke models: global, focal and lacunar. The global ischemic model is produced by occlusion of four (both vertebral and carotid arteries) or two vessels (either both carotid or vertebral arteries) with or without concomittant hypotension during ischemia period (38). In this model, global blood flow is ceased completely, which resembles the condition of cardiac arrest or coronary █ LITERATuRE REvIEw METhODS O ur review method was based on articles dealing with the relations between animal models and clinical trials. By performing a PubMed search, we aimed to identify all relevant papers to call attention to the discrepancy between experimental methodology in animal modeling and clinical experiences. Articles that were referenced by reviewed articles were also evaluated. Data from papers were extracted within the following categories: study design, type of study population, sampling strategy. Articles excluded from the review were studies that were describing surgical techniques, experimental design and methodology. █ An OvERvIEw Of STROkE MODELSThe human adult brain consumes about 8 cal/100 gr/min energy. Normally, almost 100% of glucose is metabolised, but if starved this increases up to 30%, and glucose consumption So far, animal models have helped us better understand the pathophysiology of the ischemic brain damage but they could not contribute so much to clinical practice. The discrepancies in results regarding neuroprotective agents in animal experiments compared to clinical trials have not been solved. Various animal models of ischemic stroke have proven efficacy of many neuroprotective agents without any considerable result in phase III clinical trials.As is well known, stroke-related focal cerebral ischemia or cardiac arrest related global cerebral ischemia are major causes of disability and death among human subjects. Animal models are essential to evaluate the therapeutic approaches for humans.In this review, we will try to answer two important questions: 1) Which factors endanger the reliability of experimental studies of stroke on animal models? 2) How can we design our experiments to reflect the neurorestoration and/or neuroprotection mechanisms following ischemic injury, when it comes to human disease?

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Method parameters’ impact on mortality and variability in rat stroke experiments: a meta-analysis

Cited by 52 publications

References 374 publications

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Challenges in experimental stroke research : The 17β-estradiol example

Searching evidences of stroke in animal models: a review of discrepancies

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