Improvements of the Stroke Model Guidelines Animal body weight and long-term functional concerns

Freret, Thomas; Bouët, Valentine

doi:10.4172/1939-067x.1000109

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…Weight monitoring gives an independent and unambiguous measure of an animal’s overall health and welfare [ 19 ]. For our studies, animals were weighed before surgery and then daily after stroke until the day of sacrifice.…”

Section: Methodsmentioning

confidence: 99%

RAS modulation prevents progressive cognitive impairment after experimental stroke: a randomized, blinded preclinical trial

Ahmed

Ishrat

Pillai

et al. 2018

J Neuroinflammation

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BackgroundWith the aging population, the prevalence and incidence of cerebrovascular disease will continue to rise, as well as the number of individuals with vascular cognitive impairment/dementia (VCID). No specific FDA-approved treatments for VCID exist. Although clinical evidence supports that angiotensin receptor blockers (ARBs) prevent cognitive decline in older adults, whether ARBs have a similar effect on VCID after stroke is unknown. Moreover, these agents reduce BP, which is undesirable in the acute stroke period, so we believe that giving C21 in this acute phase or delaying ARB administration would enable us to achieve the neurovascular benefits without the risk of unintended and potentially dangerous, acute BP lowering.MethodsThe aim of our study was to determine the impact of candesartan (ARB) or compound-21 (an angiotensin type 2 receptor––AT2R––agonist) on long-term cognitive function post-stroke, in spontaneously hypertensive rats (SHRs). We hypothesized that AT2R stimulation, either directly with C21, or indirectly by blocking the angiotensin type 1 receptor (AT1R) with candesartan, initiated after stroke, would reduce cognitive impairment. Animals were subjected to a 60-min transient middle cerebral artery occlusion and randomly assigned to either saline/C21 monotherapy, for the full study duration (30 days), or given sequential therapy starting with saline/C21 (7 days) followed by candesartan for the remainder of the study (21 days). Outcome measures included sensorimotor/cognitive-function, amyloid-β determination, and histopathologic analyses.ResultsTreatment with RAS modulators effectively preserved cognitive function, reduced cytotoxicity, and prevented chronic-reactive microgliosis in SHRs, post-stroke. These protective effects were apparent even when treatment was delayed up to 7 days post-stroke and were independent of blood pressure and β-amyloid accumulation.ConclusionCollectively, our findings demonstrate that RAS modulators effectively prevent cognitive impairment after stroke, even when treatment is delayed.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1262-x) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

RAS modulation prevents progressive cognitive impairment after experimental stroke: a randomized, blinded preclinical trial

Ahmed

Ishrat

Pillai

et al. 2018

J Neuroinflammation

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“…The one-way MCAO leads to contralateral neurological deficits, which manifests itself primarily asymmetry of sensory and motor functions [4,7,12,19]. Thus, the data obtained indicate significant changes in the structure of cerebral cortex and striatum in the postischemic period and the progressive nature of these changes.…”

Section: Discussionmentioning

confidence: 89%

Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

Savchuk

Skibo

2018

Rep. of Morph.

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The stroke-causing problems are extremely important in Ukraine. This makes a heavy burden not only on the health care system, but also on the whole society as a whole. That's why we've studied structural and ultrastructural changes of cortical neurons and striatum of the brain and the development of delayed death of nerve cells after the modeling of the middle cerebral artery occlusion (MCAO) and post ischemic period in rats. We've analyzed the data at different terms after modeling of MCAO. The purpose of the study was to investigate the changes in the nervous tissue in the modeling of focal cerebral ischemia by monofilament occlusion of MCAO in rats at different periods of reperfusion. The statistical processing of primary digital experimental data was carried out using the software Statistica 6.0. It was confirmed that the 60-minute occlusion of the MCAO is an adequate model of focal ischemic brain damage in rats. Changes of locomotor activity and a tactile sensitivity were determined in rats after occlusion and after reperfusion during the post-period period. It was found that in the experimental group with a reperfusion period of 72 hours, a clear increase of the volume of the ischemic area of the brain, accompanied by significant neurological deficiency, was observed. Reduced research activity of the rats was revealed, which was shown in the decrease of the number of squares they crossed, the number of racks, the increase of acts of grooming and the duration of acts of frizings. Following ischemic brain damage, there was also a disbalance of somato-sensory functions, as evidenced by an increase in the time during which the animal took a test stimulus ("Sticky tape") from both the anterior paws when tested for tactile sensitivity (adhesive removal test). An electron microscopic study of the cortex showed that dark wrinkled neurons and enlightened swollen neurons were observed at 72 hours of post-occlusion period, indicating different ways of death of these cells. Changes in striatum were similar to changes in the cortex, which progressed with an increase in the post-occlusion period. The protocol of the serial evaluation of neurological disorders used after MCAO modeling allowed detecting long-term stable functional disorders in laboratory rats. The obtained data indicate significant changes in the structure of the cortex and striatum in the post-ischemic period and the progressive nature of these changes.

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“…Weight monitoring gives an independent and unambiguous measure of an animal’s overall health and welfare [20]. Water intake was monitored periodically, over the entire course of the study.…”

Section: Methodsmentioning

confidence: 99%

“…A score of 0–3 was assigned based on the following parameters: forelimb flexion; diminished resistance to lateral push; and contralateral circling. The animal was given one point for each parameter, with lower scores indicating better performance and a score of zero indicating complete absence of a deficit [16][17] [20, 21]. In addition, swimming abilities were evaluated using the MWM (limb movement, swim speed and ability to climb onto the platform).…”

Section: Methodsmentioning

confidence: 99%

Role of angiotensin system modulation on progression of cognitive impairment and brain MRI changes in aged hypertensive animals – A randomized double- blind pre-clinical study

Ahmed

Ishrat

Pillai

et al. 2018

Behavioural Brain Research

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Growing evidence suggests that renin angiotensin system (RAS) modulators support cognitive function in various animal models. However, little is known about their long-term effects on the brain structure in aged hypertensive animals with chronic cerebral hypoperfusion as well as which specific domains of cognition are most affected. Therefore, in the current study we examined the effects of Candesartan and Compound 21 (C21) (RAS modulators) on aspects of cognition known to diminish with advanced age and accelerate with hypertension and vascular disease. Outcome measures for sensorimotor and cognitive function were performed using a sequence of tests, all blindly conducted and assessed at baseline and after 4 and 8 weeks of chronic hypoxic hypoperfusion and treatment. Magnetic resonance imaging (MRI) was performed at the end of the 8 week study period followed by animal sacrifice and tissue collection. Both Candesartan and C21 effectively preserved cognitive function and prevented progression of vascular cognitive impairment (VCI) but only candesartan prevented loss of brain volume in aged hypertensive animals. Collectively, our findings demonstrate that delayed administration of RAS modulators effectively preserve cognitive function and prevent the development / progression of VCI in aged hypertensive animals with chronic cerebral hypoperfusion.

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Improvements of the Stroke Model Guidelines Animal body weight and long-term functional concerns

Abstract: Despite extensive research efforts in the field of cerebral ischemia, numerous disappointments came out.

Cited by 4 publications

References 31 publications

RAS modulation prevents progressive cognitive impairment after experimental stroke: a randomized, blinded preclinical trial

RAS modulation prevents progressive cognitive impairment after experimental stroke: a randomized, blinded preclinical trial

Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

Role of angiotensin system modulation on progression of cognitive impairment and brain MRI changes in aged hypertensive animals – A randomized double- blind pre-clinical study

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