Focal lesions in the rat central nervous system induced by endothelin-1

P M Hughes, D C Anthony, M Ruddin, M S Botham, E L Rankine, M Sablone, D Baumann, A K Mir, V H Perry

Research output: Contribution to journalArticlepeer-review

99 Citations (SciVal)

Abstract

Axon injury following cerebral ischemia has received little scientific attention compared to the abundance of information dealing with the pathophysiology of grey matter ischemia. There are differences in the initial response of grey and white matter to ischemia in vitro. In this study we investigate whether the vasoactive peptide, endothelin-1, can generate a focal ischemic lesion in the white matter and compare the findings with endothelin-1-induced lesions in the grey matter. Using a minimally invasive technique to microinject endothelin-1 into selected brain regions, we observed an acute reduction in local MRI perfusion in the injected hemisphere after 1 hour. Twenty-four hours after microinjection of 10 pmoles of endothelin-1, we observed a loss of neurons in the grey matter. At 72 hours, neutrophils were absent and a macrophage/microglia response and astrocyte gliosis were detected. No breakdown in the blood-brain barrier was detected. After injection of 10 pmoles endothelin-1 into the cortical white matter, we observed prolific amyloid precursor protein-positive immunostaining (indicative of axonal disruption) and an increase in tau-1 immunostaining in oligodendrocytes at 6 hours. Similar to the grey matter lesions, no neutrophils were present, a macrophage/microglia response did not occur until 72 hours and there was no disruption in the blood-brain barrier. Focal injections of endothelin-1 into specific areas of the rat CNS represent a model to investigate therapeutic approaches to white matter ischemia.

Original languageEnglish
Pages (from-to)1276-1286
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number12
DOIs
Publication statusPublished - 01 Dec 2003
Externally publishedYes

Keywords

  • Animals
  • Brain/drug effects
  • Brain Ischemia/chemically induced
  • Central Nervous System/drug effects
  • Endothelin-1/toxicity
  • Male
  • Rats
  • Rats, Wistar
  • Rat
  • Central nervous system
  • Inflammation
  • Axonal damage
  • White matter
  • Ischemia
  • Endothelin-1

Fingerprint

Dive into the research topics of 'Focal lesions in the rat central nervous system induced by endothelin-1'. Together they form a unique fingerprint.

Cite this