Neuroprotective effects of erythromycin on ischemic injury following permanent focal cerebral ischemia in rats

Neurol Res. 2016 Mar;38(3):275-84. doi: 10.1080/01616412.2016.1138662. Epub 2016 Mar 16.

Abstract

Objective: This study aims to determine if erythromycin provides neuroprotective effects against ischemic injury following permanent focal cerebral ischemia.

Methods: Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Each animal received a single subcutaneous injection of erythromycin lactobionate (EM, 50 mg/kg) or vehicle immediately after ischemia. The infarct volume, edema index and neurological performance were evaluated at 24 and 72 h after MCAO. The cerebral blood flow (CBF) was measured with an MRI system at 30 min after MCAO. TUNEL staining and immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) in the cortex were conducted at 24 and 72 h after MCAO.

Results: The CBF did not differ between the EM-treated and vehicle-treated groups. The EM treatment significantly reduced the infarct volume (p < 0.01) at 24 and 72 h after MCAO and significantly reduced the edema index (p < 0.01) at 24 h. The EM treatment significantly improved the neurological deficit scores (p < 0.05) at 24 and 72 h. EM also significantly suppressed the accumulation of 4-HNE (p < 0.01) and 8-OHdG (p < 0.01) and markedly reduced Iba-1 (p < 0.01) and TNF-α expression (p < 0.05) at both time points. The EM treatment significantly reduced TUNEL-positive cells (p < 0.01) at both time points.

Conclusion: These findings suggest that EM can protect against the neuronal damage caused by cerebral ischemia by alleviating inflammation and reducing oxidant stress.

Keywords: Anti-inflammatory action; Antioxidant action; Erythromycin; Permanent ischemia.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aldehydes / metabolism
  • Animals
  • Blood Pressure / drug effects
  • Body Temperature / drug effects
  • Brain Edema / drug therapy
  • Brain Edema / etiology
  • Brain Infarction / drug therapy
  • Brain Infarction / etiology
  • Brain Injuries / diagnostic imaging
  • Brain Injuries / drug therapy*
  • Brain Injuries / etiology*
  • Calcium-Binding Proteins / metabolism
  • Cerebrovascular Circulation / drug effects
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Erythromycin / therapeutic use*
  • In Situ Nick-End Labeling
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / diagnostic imaging
  • Magnetic Resonance Imaging
  • Microfilament Proteins / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Statistics, Nonparametric
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aif1 protein, rat
  • Aldehydes
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Erythromycin
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • 4-hydroxy-2-nonenal