Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Etherton, Mark R.; Wu, Ona; Cougo, Pedro; Lorenzano, Svetlana; Li, Hua; Cloonan, Lisa; Bouts, Mark J. R. J.; Lauer, Arne; Arai, Ken; Lo, Eng H.; Feske, Steve K.; Furie, Karen L.; Rost, Natalia S.

doi:10.1136/svn-2019-000268

Cited by 11 publications

(4 citation statements)

References 42 publications

(55 reference statements)

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“…By these means, it may eventually be possible to quantify the clinical importance of sex-specific lesion patterns by taking into account their modifying effects on acute recanalization treatments. Since some evidence for example suggests sex-specific effects of white matter integrity on stroke outcome 66 , further future studies may also not only include acute, but also chronic markers of brain health while taking sex into account more closely.…”

Section: Discussionmentioning

confidence: 99%

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

et al. 2021

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Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

et al. 2021

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“…This study was limited to experiments on young male mice and future studies must consider the use of female animals and co-morbidities. Sex dimorphism of cerebral vessels and CBF have been observed in both stroke patients 32 – 34 and in rodent stroke models. 35 – 37 Stroke is also an age-related disease and strongly affects patients with co-morbidities.…”

Section: Discussionmentioning

confidence: 99%

Preconditioning with interleukin-1 alpha is required for the neuroprotective properties of mesenchymal stem cells after ischemic stroke in mice

Wong,

Smith,

Allan

et al. 2023

J Cereb Blood Flow Metab

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Mesenchymal stem cell (MSC) pre-conditioning with interleukin-1 alpha (IL-1ɑ) drives MSCs toward a potent anti-inflammatory phenotype. The aim of this study was to assess the therapeutic potential of intra-arterially administered IL-1ɑ preconditioned MSCs, after experimental cerebral ischaemia in mice. After 3 h from the start of middle cerebral artery occlusion, animals were treated with vehicle, 9.1 × 104 non-conditioned or IL-1ɑ preconditioned MSCs by intra-arterial administration. Animals were allowed to recover for 1.5 h after treatment to measure cerebral blood flow (CBF), and 3 days or 14 days post-stroke to evaluate lesion volume and functional outcomes. At 3-days post-stroke preconditioned MSCs reduced (by 67%) lesion volume and increased CBF (by 32%) compared to vehicle, while non-conditioned MSCs had no effect. A separate cohort of animals recovered to 14 days post-stroke also showed reduced infarct volume (by 51%) at 48 h (assessed by MRI) and better functional recovery at 14 days when treated with preconditioned MSCs when compared to vehicle. Preconditioning MSCs with IL-1α increases their neuroprotective capability and improves functional recovery after delayed intra-arterial administration. With increasing use of thrombectomy, the adjunct use of preconditioned MSCs therefore represents a highly relevant therapy to improve outcomes in ischaemic stroke.

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“…According to epidemiological data, stroke is a sexually dimorphic disease ( 9 , 10 ). Although the incidence of stroke is much higher in men, women have been reported to have severe CNS injuries, higher morbidity and mortality, and greater post-stroke neurobehavioral deficits.…”

Section: Incidence and Severity Of Ischemic Stroke Based On Sexmentioning

confidence: 99%

Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex

Zhong¹,

Sun²,

Lü³

et al. 2023

Front. Immunol.

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Although estrogen is predominantly related to the maintenance of reproductive functioning in females, it mediates various physiological effects in nearly all tissues, especially the central nervous system. Clinical trials have revealed that estrogen, especially 17β-estradiol, can attenuate cerebral damage caused by an ischemic stroke. One mechanism underlying this effect of 17β-estradiol is by modulating the responses of immune cells, indicating its utility as a novel therapeutic strategy for ischemic stroke. The present review summarizes the effect of sex on ischemic stroke progression, the role of estrogen as an immunomodulator in immune reactions, and the potential clinical value of estrogen replacement therapy. The data presented here will help better understand the immunomodulatory function of estrogen and may provide a basis for its novel therapeutic use in ischemic stroke.

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Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Cited by 11 publications

References 42 publications

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Preconditioning with interleukin-1 alpha is required for the neuroprotective properties of mesenchymal stem cells after ischemic stroke in mice

Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex

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