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Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats.

Schreiber S, Bueche CZ, Garz C, Kropf S, Kuester D, Amann K, Heinze HJ, Goertler M, Reymann KG, Braun H - PLoS ONE (2011)

Bottom Line: The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts.Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology.Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany. stefanie.schreiber@med.ovgu.de

ABSTRACT

Introduction: Human cerebral small vessel disease (CSVD) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of human CSVD. Here we compare renal histopathological changes with the brain pathology of spontaneously hypertensive stroke-prone rats (SHRSP).

Material and methods: We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, glomerulosclerosis) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP.

Results: Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal tubulointerstitial damage characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts.

Conclusion: Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage.

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Related in: MedlinePlus

Kidney and brain morphology of a control and SHRSP with few cerebral erythrocyte accumulations.Both the kidney medulla (A) and cortex (B) of a 32 weeks old Wistar rat are free of peritubular erythrocyte aggregations, tubular protein cylinders, glomerulosclerosis and thrombotic microangiopathy which corresponds to normal brain morphology (here hippocampus, C). In contrast the kidney of an 18 weeks old SHRSP (animal 6) shows a few erythrocyte aggregations in medullar peritubular capillaries (D & D') and erythrocyte sticking (black arrow heads in E & E') in few glomeruli (E & E'). This pathology corresponds to mild erythrocyte accumulations (beginning stases) within some capillaries of the brain (here hippocampus, F & F'). Wistar-32: wistar control, 32 weeks old; A006-18: animal number 6, 18 weeks old.
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pone-0026287-g002: Kidney and brain morphology of a control and SHRSP with few cerebral erythrocyte accumulations.Both the kidney medulla (A) and cortex (B) of a 32 weeks old Wistar rat are free of peritubular erythrocyte aggregations, tubular protein cylinders, glomerulosclerosis and thrombotic microangiopathy which corresponds to normal brain morphology (here hippocampus, C). In contrast the kidney of an 18 weeks old SHRSP (animal 6) shows a few erythrocyte aggregations in medullar peritubular capillaries (D & D') and erythrocyte sticking (black arrow heads in E & E') in few glomeruli (E & E'). This pathology corresponds to mild erythrocyte accumulations (beginning stases) within some capillaries of the brain (here hippocampus, F & F'). Wistar-32: wistar control, 32 weeks old; A006-18: animal number 6, 18 weeks old.

Mentions: In a former study we demonstrated the proceeding of the cerebral vascular pathology in SHRSP in definite stages [13]. Thereby an accumulation of erythrocytes in the small vessels of the whole brain seemed to represent the homogeneous initial step of the disease (Figure 2 F & Figure 3 C, F). We referred to these accumulated erythrocytes parsimoniously as stases. The number of SHRSP with accumulated erythrocytes significantly increased with age. In SHRSP aged 28 weeks and older erythrocyte accumulations occurred in both, capillaries and arteriolar segments (Figure 3 F), whereas the accumulated erythrocytes found in younger animals (12 to 26 weeks) were seen predominantly in capillaries (Figure 2 F & Figure 3 C). About 60% of the SHRSP aged 12 weeks exhibited erythrocyte accumulations. Interestingly, at the age of 28 weeks we found accumulated erythrocytes in all investigated SHRSP (Table S1).


Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats.

Schreiber S, Bueche CZ, Garz C, Kropf S, Kuester D, Amann K, Heinze HJ, Goertler M, Reymann KG, Braun H - PLoS ONE (2011)

Kidney and brain morphology of a control and SHRSP with few cerebral erythrocyte accumulations.Both the kidney medulla (A) and cortex (B) of a 32 weeks old Wistar rat are free of peritubular erythrocyte aggregations, tubular protein cylinders, glomerulosclerosis and thrombotic microangiopathy which corresponds to normal brain morphology (here hippocampus, C). In contrast the kidney of an 18 weeks old SHRSP (animal 6) shows a few erythrocyte aggregations in medullar peritubular capillaries (D & D') and erythrocyte sticking (black arrow heads in E & E') in few glomeruli (E & E'). This pathology corresponds to mild erythrocyte accumulations (beginning stases) within some capillaries of the brain (here hippocampus, F & F'). Wistar-32: wistar control, 32 weeks old; A006-18: animal number 6, 18 weeks old.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198774&req=5

pone-0026287-g002: Kidney and brain morphology of a control and SHRSP with few cerebral erythrocyte accumulations.Both the kidney medulla (A) and cortex (B) of a 32 weeks old Wistar rat are free of peritubular erythrocyte aggregations, tubular protein cylinders, glomerulosclerosis and thrombotic microangiopathy which corresponds to normal brain morphology (here hippocampus, C). In contrast the kidney of an 18 weeks old SHRSP (animal 6) shows a few erythrocyte aggregations in medullar peritubular capillaries (D & D') and erythrocyte sticking (black arrow heads in E & E') in few glomeruli (E & E'). This pathology corresponds to mild erythrocyte accumulations (beginning stases) within some capillaries of the brain (here hippocampus, F & F'). Wistar-32: wistar control, 32 weeks old; A006-18: animal number 6, 18 weeks old.
Mentions: In a former study we demonstrated the proceeding of the cerebral vascular pathology in SHRSP in definite stages [13]. Thereby an accumulation of erythrocytes in the small vessels of the whole brain seemed to represent the homogeneous initial step of the disease (Figure 2 F & Figure 3 C, F). We referred to these accumulated erythrocytes parsimoniously as stases. The number of SHRSP with accumulated erythrocytes significantly increased with age. In SHRSP aged 28 weeks and older erythrocyte accumulations occurred in both, capillaries and arteriolar segments (Figure 3 F), whereas the accumulated erythrocytes found in younger animals (12 to 26 weeks) were seen predominantly in capillaries (Figure 2 F & Figure 3 C). About 60% of the SHRSP aged 12 weeks exhibited erythrocyte accumulations. Interestingly, at the age of 28 weeks we found accumulated erythrocytes in all investigated SHRSP (Table S1).

Bottom Line: The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts.Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology.Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany. stefanie.schreiber@med.ovgu.de

ABSTRACT

Introduction: Human cerebral small vessel disease (CSVD) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of human CSVD. Here we compare renal histopathological changes with the brain pathology of spontaneously hypertensive stroke-prone rats (SHRSP).

Material and methods: We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, glomerulosclerosis) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP.

Results: Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal tubulointerstitial damage characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts.

Conclusion: Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage.

Show MeSH
Related in: MedlinePlus