Aging aggravates long-term renal ischemia-reperfusion injury in a rat model

Aim

Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI.

Materials and methods

Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed.

Results

Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI.

Conclusion

Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI.     

Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...     

A homozygous mutation in the NDUFS1 gene presents with a mild cavitating leukoencephalopathy

We report a case of mild cavitating leukoencephalopathy associated with a homozygous c.755A > G (p.Asp252Gly) NDUFS1 mutation in a 7-year old boy. Biochemical analysis confirmed an isolated reduction in complex I activity. Magnetic resonance imaging of the brain showed a diffuse cystic leukoencephalopathy with the involvement of the corpus callosum and sparing of the gray matter. The clinical course was marked by an acute presentation of neurological deficits at 24 months followed by recurrent episodes of mild neurological deterioration, subsequent remissions, and prolonged periods of stability. This is one of the mildest known clinical presentations of complex I deficiency secondary to mutations in NDUFS1, expanding the clinical spectrum and natural history of this disorder. Consideration of clinical variability needs to be taken into account in patient management and family counseling.     

OCTA Derived Vessel Skeleton Density Versus Flux and Their Associations With Systemic Determinants of Health

PurposeTo examine the associations of optical coherence tomography angiography (OCTA)–derived retinal capillary flux with systemic determinants of health.MethodsThis is a cross-sectional study of subjects recruited from the African American Eye Disease Study. A commercially available swept-source (SS)-OCTA device was used to image the central 3 × 3 mm macular region. Retinal capillary perfusion was assessed using vessel skeleton density (VSD) and flux. Flux approximates the number of red blood cells moving through vessel segments and is a novel metric, whereas VSD is a previously validated measure commonly used to quantify capillary density. The associations of OCTA derived measures with systemic determinants of health were evaluated using multivariate generalized linear mixed-effects models.ResultsA total of 154 eyes from 83 participants were enrolled. Mean VSD and flux were 0.148 ± 0.009 and 0.156 ± 0.016, respectively. In a model containing age, systolic blood pressure, diabetes status, hematocrit, and presence of retinopathy as covariates, there was a negative correlation between VSD and age (P < 0.001) and retinopathy (P = 0.02), but not with hematocrit (P = 0.85) or other factors. There was a positive correlation between flux and hematocrit (P = 0.02), as well as a negative correlation for flux with age (P < 0.001), systolic blood pressure (P = 0.04), and diabetes status (P = 0.02). A 1% decrease in hematocrit was associated with the same magnitude change in flux as ∼1.24 years of aging. Signal strength was associated with flux (P < 0.001), but not VSD (P = 0.51).ConclusionsSS-OCTA derived flux provides additional information about retinal perfusion distinct from that obtained with skeleton density-based measures. Flux is appropriate for detecting subclinical changes in perfusion in the absence of clinical retinopathy.