Limits...
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.

Show MeSH

Related in: MedlinePlus

Severe kidney pathology in SHRSP corresponds to final stages of cerebral vascular pathology.A–C: SHRSP (animal 2, 34 weeks old) with cerebral microbleeds. D–F: SHRSP (animal 4, 31 weeks old) with cerebral infarctions containing small vessel occlusions. There is a strong correlation between an advanced kidney pathology, i.e. peritubular aggregations of erythrocytes, protein cylinders and different stages of glomerulosclerosis with cerebral infarctions accompanied by either microbleeds (here hippocampus, C) or small vessel occlusions with surrounding necrotic tissue (F). A & D: kidney medulla, B & E: kidney cortex, peritubular aggregations of erythrocytes are marked by black dashed lines (A & D), protein cylinders by white asterisks (A, B & D). Different stages of glomerulosclerosis are marked in B & E (o, x; see also Figure 5). In addition kidney vessels are affected by thrombotic microangiopathy (+ in B). B corresponds to Figure 5 E. A002-34: animal number 2, 34 weeks old.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198774&req=5

pone-0026287-g004: Severe kidney pathology in SHRSP corresponds to final stages of cerebral vascular pathology.A–C: SHRSP (animal 2, 34 weeks old) with cerebral microbleeds. D–F: SHRSP (animal 4, 31 weeks old) with cerebral infarctions containing small vessel occlusions. There is a strong correlation between an advanced kidney pathology, i.e. peritubular aggregations of erythrocytes, protein cylinders and different stages of glomerulosclerosis with cerebral infarctions accompanied by either microbleeds (here hippocampus, C) or small vessel occlusions with surrounding necrotic tissue (F). A & D: kidney medulla, B & E: kidney cortex, peritubular aggregations of erythrocytes are marked by black dashed lines (A & D), protein cylinders by white asterisks (A, B & D). Different stages of glomerulosclerosis are marked in B & E (o, x; see also Figure 5). In addition kidney vessels are affected by thrombotic microangiopathy (+ in B). B corresponds to Figure 5 E. A002-34: animal number 2, 34 weeks old.

Mentions: When the SHRSP reached an age of about 32 weeks we detected extraluminal fresh microbleeds characterized by numerous grouped erythrocytes leaking from the small vessels into the parenchyma (Figure 4 C). Microthromboses (Figure 4 F) with subsequent cerebral infarctions characterized by spongy and cystic tissue destruction represent the final step in the pathological cascade of the cerebral vascular pathology in SHRSP.


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)

Severe kidney pathology in SHRSP corresponds to final stages of cerebral vascular pathology.A–C: SHRSP (animal 2, 34 weeks old) with cerebral microbleeds. D–F: SHRSP (animal 4, 31 weeks old) with cerebral infarctions containing small vessel occlusions. There is a strong correlation between an advanced kidney pathology, i.e. peritubular aggregations of erythrocytes, protein cylinders and different stages of glomerulosclerosis with cerebral infarctions accompanied by either microbleeds (here hippocampus, C) or small vessel occlusions with surrounding necrotic tissue (F). A & D: kidney medulla, B & E: kidney cortex, peritubular aggregations of erythrocytes are marked by black dashed lines (A & D), protein cylinders by white asterisks (A, B & D). Different stages of glomerulosclerosis are marked in B & E (o, x; see also Figure 5). In addition kidney vessels are affected by thrombotic microangiopathy (+ in B). B corresponds to Figure 5 E. A002-34: animal number 2, 34 weeks old.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0026287-g004: Severe kidney pathology in SHRSP corresponds to final stages of cerebral vascular pathology.A–C: SHRSP (animal 2, 34 weeks old) with cerebral microbleeds. D–F: SHRSP (animal 4, 31 weeks old) with cerebral infarctions containing small vessel occlusions. There is a strong correlation between an advanced kidney pathology, i.e. peritubular aggregations of erythrocytes, protein cylinders and different stages of glomerulosclerosis with cerebral infarctions accompanied by either microbleeds (here hippocampus, C) or small vessel occlusions with surrounding necrotic tissue (F). A & D: kidney medulla, B & E: kidney cortex, peritubular aggregations of erythrocytes are marked by black dashed lines (A & D), protein cylinders by white asterisks (A, B & D). Different stages of glomerulosclerosis are marked in B & E (o, x; see also Figure 5). In addition kidney vessels are affected by thrombotic microangiopathy (+ in B). B corresponds to Figure 5 E. A002-34: animal number 2, 34 weeks old.
Mentions: When the SHRSP reached an age of about 32 weeks we detected extraluminal fresh microbleeds characterized by numerous grouped erythrocytes leaking from the small vessels into the parenchyma (Figure 4 C). Microthromboses (Figure 4 F) with subsequent cerebral infarctions characterized by spongy and cystic tissue destruction represent the final step in the pathological cascade of the cerebral vascular pathology in SHRSP.

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