Correlation Between Motor Impairment and Infarct Volume After Permanent and Transient Middle Cerebral Artery Occlusion in the Rat

Rogers, Derek C.; Campbell, C. A.; Stretton, Jennifer L.; Mackay, Kenneth B.

doi:10.1161/01.str.28.10.2060

Cited by 365 publications

(241 citation statements)

References 31 publications

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“…Data are expressed as mean7s.d. rats has been shown to cause significant motor impairments, as assessed using the rotarod and grid test (Rogers et al, 1997). This was found, in the present study, to be true also in mice.…”

Section: Discussionsupporting

confidence: 82%

“…In addition, these previous studies give no clue as to any longerterm benefits of G-CSF treatment after stroke. While some argue that infarct size correlates well with certain neurologic deficits (Rogers et al, 1997), this is certainly not always the case (Hattori et al, 2000;Reglodi et al, 2003). Functional outcomes are more useful in terms of assessing the benefit of a treatment after stroke.…”

Section: Introductionmentioning

confidence: 99%

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G-CSF Reduces Infarct Volume and Improves Functional Outcome after Transient Focal Cerebral Ischemia in Mice

Gibson

Bath

Murphy

2005

J Cereb Blood Flow Metab

155

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Growth factors possess neuroprotective and neurotrophic properties in vitro, but few have been extensively studied in vivo after stroke. In the present study, we investigated the potential functional benefits of granulocyte colony-stimulating factor (G-CSF) administration after focal cerebral ischemia. Male mice underwent 60-minute middle cerebral artery occlusion (MCAO) and received G-CSF (50 lg/kg, subcutaneously) or vehicle (saline) at the onset of reperfusion. Granulocyte colony-stimulating factor-treated mice killed at 48 hours after MCAO revealed a 445% reduction (Po0.05) in lesion volume. In terms of body weight recovery, and in tests of motor (grid test and rotarod) and cognitive ability (water maze), MCAO significantly worsened the outcome in vehicletreated mice as compared with shams (Po0.05). However, G-CSF treatment was beneficial as, compared with vehicle, this significantly improved weight recovery and motor ability. This effect was most apparent on the water maze where G-CSF-treated mice were indistinguishable from shams in terms of acquiring the task. These results indicate long-term beneficial effects of a single dose of G-CSF administered on reperfusion, and illustrate the need to further investigate the mechanisms of G-CSF action.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

G-CSF Reduces Infarct Volume and Improves Functional Outcome after Transient Focal Cerebral Ischemia in Mice

Gibson

Bath

Murphy

2005

J Cereb Blood Flow Metab

155

View full text Add to dashboard Cite

show abstract

“…Also, preclinical studies have shown that transient middle cerebral artery occlusion (MCA) occlusion plus reperfusion causes less damage than permanent MCA occlusion in rats (Memezawa et al, 1992;Rogers et al, 1997). However, reperfusion carries some risks, such as hemorrhagic transformation and fatal edema, which could be attributed, at least in part, to reperfusion injury (Pan et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant CR-6 Protects against Reperfusion Injury after a Transient Episode of Focal Brain Ischemia in Rats

Pérez-Asensio

Rosa

Jiménez‐Altayó

et al. 2009

J Cereb Blood Flow Metab

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Oxidative and nitrosative stress are targets for intervention after ischemia/reperfusion. The aim of this study was to explore the effect of CR-6, a vitamin-E analogue that is antioxidant and scavenger of nitrogen-reactive species. Sprague-Dawley rats had the middle cerebral artery (MCA) occluded either for 90 mins or permanently. Cortical perfusion was continuously monitored by laser-Doppler flowmetry. CR-6 (100 mg/kg) was administered orally either at 2 and 8 h after MCA occlusion, or at 2 h only. Infarct volume, neurological deficit, and signs of reperfusion injury were evaluated. CR-6 was detected in plasma and brain by HPLC. CR-6 reduced glutathione consumption in the ischemic brain and superoxide generation in the isolated MCA. CR-6 decreased infarct volume and attenuated the neurological deficit at 1 and 7 days after ischemia/reperfusion, but not after permanent ischemia. Immediately after reperfusion, cortical blood flow values returned to their baseline ( ± 20%) in several animals, whereas others showed hyper-perfusion ( > 20% of baseline). Reactive hyperemia was associated with adverse events such as increased cortical BBB leakage, edema, protein nitrotyrosination, COX-2 expression, and neutrophil accumulation; and with a poorer outcome, and CR-6 attenuated these effects. In conclusion, oral CR-6 administration after transient ischemia protects the brain from reperfusion injury.

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“…It is important to note that the improved behavioral recovery in multiparous females may simply reflect the smaller infarct seen in these mice rather than an enhanced delayed angiogenic response. Behavioral deficits and recovery are known to be related to the location and severity of the initial stroke injury (30,31). However, the near complete preservation of sensorimotor and cognitive function in the multiparous mice is nonetheless impressive, given that the striatal infarct was prominent in both groups.…”

Section: Discussionmentioning

confidence: 99%

Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk

Ritzel

Patel

Spychala

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Females show a varying degree of ischemic sensitivity throughout their lifespan, which is not fully explained by hormonal or genetic factors. Epidemiological data suggest that sex-specific life experiences such as pregnancy increase stroke risk. This work evaluated the role of parity on stroke outcome. Age-matched virgin (i.e., nulliparous) and multiparous mice were subjected to 60 min of reversible middle cerebral artery occlusion and evaluated for infarct volume, behavioral recovery, and inflammation. Using an established mating paradigm, fetal microchimeric cells present in maternal mice were also tracked after parturition and stroke. Parity was associated with sedentary behavior, weight gain, and higher triglyceride and cholesterol levels. The multiparous brain exhibited features of immune suppression, with dampened baseline microglial activity. After acute stroke, multiparous mice had smaller infarcts, less glial activation, and less behavioral impairment in the critical recovery window of 72 h. Behavioral recovery was significantly better in multiparous females compared with nulliparous mice 1 mo after stroke. This recovery was accompanied by an increase in poststroke angiogenesis that was correlated with improved performance on sensorimotor and cognitive tests. Multiparous mice had higher levels of VEGF, both at baseline and after stroke. GFP + fetal cells were detected in the blood and migrated to areas of tissue injury where they adopted endothelial morphology 30 d after injury. Reproductive experience has profound and complex effects on neurovascular health and disease. Inclusion of female mice with reproductive experience in preclinical studies may better reflect the life-long patterning of ischemic stroke risk in women.sex differences | multiparity | microglia | ischemic stroke | microchimerism N early 800,000 people in the United States experience a new or recurrent stroke each year, and 55,000 more women than men are affected by stroke (1). Stroke is a sexually dimorphic disease impacted by genetics, hormones, and the environment (2). According to CDC data, 85% of women in the United States have given birth by age 40, whereas the number of lifetime pregnancies per woman varies by race and socioeconomic status. Therefore, child-bearing women represent a significant proportion of the female population, including those at risk for stroke. Moreover, this suggests that a large proportion of the elderly female populationwho is at highest risk for stroke-may be differentially at risk. Epidemiological data suggest that increasing parity is associated with higher risk of cardiovascular disease (CVD) and stroke and late-life vascular comorbidities, including carotid atherosclerosis (3, 4). However, recent reports suggest that parity has a significant protective effect against CVD mortality (5). The effect of parity on outcome following ischemic stroke is yet unresolved.Pregnancy induces profound acute and long-term physiological changes in the body that influence future vascular health through hormonally med...

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Correlation Between Motor Impairment and Infarct Volume After Permanent and Transient Middle Cerebral Artery Occlusion in the Rat

Cited by 365 publications

References 31 publications

G-CSF Reduces Infarct Volume and Improves Functional Outcome after Transient Focal Cerebral Ischemia in Mice

G-CSF Reduces Infarct Volume and Improves Functional Outcome after Transient Focal Cerebral Ischemia in Mice

Antioxidant CR-6 Protects against Reperfusion Injury after a Transient Episode of Focal Brain Ischemia in Rats

Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk

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