Iron accumulation and microglia activation contribute to substantia nigra hyperechogenicity in the 6-OHDA-induced rat model of Parkinson's disease

Parkinsonism Relat Disord. 2017 Mar:36:76-82. doi: 10.1016/j.parkreldis.2017.01.003. Epub 2017 Jan 6.

Abstract

Introduction: This study aims to explain the mechanisms for the formation of sonographic features of Parkinson's disease (PD) using a 6-hydroxydopamine (6-OHDA) rat model of PD. The iron chelator deferiprone (DFP) was used in the PD model rat to examine the relationship between iron and the echo signal.

Methods: Rat models were created using stereotactic injections of 6-OHDA. DFP was administered intragastrically. Transcranial sonography (TCS) was performed to observe the substantia nigra (SN) echo signal of the brain. Immunofluorescence and iron staining were performed to observe the histological characteristics of the hyperechogenic area. The imaging findings were compared with the histopathological findings.

Results: The PD model rat presented a large area of hyperechogenicity in the SN. Ferric ion accumulation and microglia proliferation occurred in the hyperechogenic area. DFP inhibited dopaminergic (DA) neuron necrosis, ferric ion accumulation and microglia proliferation and reduced the hyperechogenic area of the SN.

Conclusions: Both iron aggregation and gliosis contribute to the formation of substantia nigra hyperechogenicity (SNH) in PD. DFP exhibits a neuroprotective effect by inhibiting SNH. Iron deposit and the SNH are correlated with DA neuron necrosis.

Keywords: 6-Hydroxydopamine; Deferiprone; Parkinson's disease; Substantia nigra hyperechogenicity; Transcranial sonography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Iron / metabolism*
  • Male
  • Microglia / metabolism*
  • Microglia / pathology
  • Oxidopamine / toxicity*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / diagnostic imaging
  • Parkinsonian Disorders / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / diagnostic imaging
  • Substantia Nigra / metabolism*

Substances

  • Oxidopamine
  • Iron