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Translational Stroke Research

, Volume 4, Issue 3, pp 351–367 | Cite as

Characterisation of Endothelin-1-Induced Intrastriatal Lesions Within the Juvenile and Adult Rat Brain Using MRI and 31P MRS

  • Raman Saggu
Original Article
  • 208 Downloads

Abstract

Improved non-invasive magnetic resonance (MR) characterisation of in vivo models of focal ischaemic insults such as transient ischaemic attack (TIA) and perinatal arterial ischaemic stroke (AIS) may assist diagnosis, outcome prediction and treatment design. The classic middle cerebral artery occlusion (MCAO) model of ischaemic stroke is well documented in MR studies but generates extensive and complex lesions involving an acute inflammatory response and de-occlusion that immediately restores circulation. By contrast, intrastriatal microinjection of the potent vasoconstrictor, endothelin-1 (ET-1), induces a focal, reversible and low-flow ischaemia in the absence of a typical inflammatory response, which gradually restores blood flow over several hours and may be more relevant to TIA and AIS pathology. This study presents the first comprehensive longitudinal MR characterisation of the real-time anatomical [T1-weighted (T1-w)/T2-weighted (T2-w)], pathophysiological [apparent diffusion coefficient (ADC), cerebral blood volume, gadolinium contrast imaging of blood–brain barrier (BBB) integrity] and metabolic [phosphorus magnetic resonance spectroscopy (31P MRS)] evolution of a purely ischaemic ET-1-induced lesion within the juvenile and adult rat brain. ET-1-induced cytotoxic oedema was visualised on T2-w magnetic resonance imaging (MRI), inconsistent with the conventional notion that it cannot be detected using anatomical MRI. There was no immunohistochemical evidence of an acute inflammatory response or loss of BBB integrity, thus excluding a vasogenic oedema contribution to the pathology. Maximal T2-w intensity correlated with the lowest ADC value in both age groups, re-emphasising the purely ischaemic nature of the lesion and the absence of vasogenic oedema. Furthermore, extensive acute T1-w hypointensity was observed in the presence of cytotoxic oedema-induced T2-w changes, whereas other authors have shown that increased T1 values following MCAO reflect vasogenic oedema. Intriguingly, the lesion border exhibited hyperintensity on T2-w and ADC MRI at later time points, and the former may be a consequence of phagocytosis-induced fatty droplet deposition by macrophages detected immunohistochemically. In spite of a chronically reduced ADC, typically associated with ischaemia-induced energy failure, a 31P MRS-detectable reduction in the phosphocreatine (PCr) to gamma adenosine triphosphate (γATP) ratio was not observed at any time point in either age group, suggesting dissociation of tissue water diffusion and metabolic changes within the ET-1-induced lesion.

Keywords

Endothelin-1 Stroke Ischaemia Magnetic resonance imaging Phosphorus magnetic resonance spectroscopy Apparent diffusion coefficient Brain 

Abbreviations

ADC

Apparent diffusion coefficient

31P MRS

Phosphorus magnetic resonance spectroscopy

BBB

Blood–brain barrier

ATP

Adenosine triphosphate

PCr

Phosphocreatine

CK

Creatine kinase

γ

Gamma

CBV

Cerebral blood volume

Notes

Acknowledgments

The author would like to thank Dr. John P. Lowe for expertise in MR data acquisition/analysis and Dr. Yann Le Fur for the software programme for integration of the phosphorus spectra. Thanks are also due to the late Professor Alison Brading for helpful discussion and to Professor Frances Platt, Professor Mehmet Bilgen and Professor Raymond Dwek for their invaluable advice and guidance. Raman Saggu is the recipient of a Medical Research Council (MRC) UK D.Phil. (University of Oxford) Studentship and Wolfson College Oxford Hardship Fund and Senior Tutor Loan.

Conflict of Interest

The author declares no conflict of interest.

Supplementary material

12975_2013_258_MOESM1_ESM.doc (40 kb)
ESM 1 (DOC 40 kb)

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.MRC Biochemical and Clinical Magnetic Resonance Unit, Department of BiochemistryUniversity of OxfordOxfordUnited Kingdom

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