Abstract
Compelling evidence indicates that factors in the blood can profoundly reverse aging-related impairments, as exposure of aged mice to young blood rejuvenates adult stem cell function, improves cognition, and ameliorates cardiac hypertrophy. Systemic factors from mice can also extend the life span of a partner exposed to a lethal treatment or disease. These findings suggest that the systemic milieu of a healthy young partner may be beneficial for an aged organism. However, it is unknown whether a healthy young systemic milieu can improve functional recovery after ischemic stroke. Intraperitoneal administration of young plasma into aged rats after ischemic stroke induced by distal middle cerebral artery occlusion (dMCAO) reduced infarct volume and motor impairment, compared with vehicle group. On the contrary, intraperitoneal administration of plasma from aged rats into young ischemic rats worsened brain injury and motor deficits. Using a proteomic approach, we found that haptoglobin levels were significantly increased in serum of aged rats and that intraperitoneal administration of haptoglobin impaired outcome after ischemic stroke in young rats. Our data suggest that the aging systemic milieu plays a critical role in functional outcome after ischemic stroke.
Highlights
Aging is associated with a striking increase in the incidence of ischemic stroke, which is a leading cause of disability among those age 70 years and older [1]
Young or old plasma was intraperitoneally injected into young rats1 hr after the onset of ischemia (Fig. 1A) and histologic outcome was assessed by measuring infarct size, determined by TTC staining of coronal brain slices [10] (Fig. 1B)
We found that systemic administration of young plasma into an aged ischemic rat reduced infarct volume and improved neurobehavioral deficit, while exposing a young ischemic rat to plasma from aged rats had the opposite effects
Summary
Aging is associated with a striking increase in the incidence of ischemic stroke, which is a leading cause of disability among those age 70 years and older [1]. Systemic administration of young plasma to aged mice increased neurogenesis and improved agerelated cognitive impairments [2, 6], while exposing a young mouse to an old systemic milieu or to plasma from old mice impaired cognitive function [6] These observations suggest that cognitive impairments during aging may be attributed in part to changes in blood-borne systemic factors [2, 6]. A recent study documented that a healthy mouse could extend the life span of a partner exposed to a lethal treatment or disease through heterochronic parabiosis [7] Taken together, these findings indicate that signals from the systemic milieu are closely associated with the brain dysfunction, and raise questions about the role of systemic factors in worsened functional recovery after ischemic stroke and the therapeutic potential of blood-borne factors from young organisms. Our data suggest that the aging systemic milieu plays a critical role in functional recovery after ischemic stroke, and elucidates a previously unrecognized role for haptoglobin in the prognosis of ischemic stroke
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