PPAR- γ Promotes Hematoma Clearance through Haptoglobin-Hemoglobin-CD163 in a Rat Model of Intracerebral Hemorrhage

Behav Neurol. 2018 Jul 9:2018:7646104. doi: 10.1155/2018/7646104. eCollection 2018.

Abstract

Background and purpose: PPAR-γ is a transcriptional factor which is associated with promoting hematoma clearance and reducing neurological dysfunction after intracerebral hemorrhage (ICH). Haptoglobin- (Hp-) hemoglobin- (Hb-) CD163 acts as a main pathway to Hb scavenging after ICH. The effect of PPAR-γ on the Hp-Hb-CD163 signaling pathway has not been reported. We hypothesized that PPAR-γ might protect against ICH-induced neuronal injury via activating the Hp-Hb-CD163 pathway in a rat ICH model.

Methods: 107 Sprague-Dawley rats were used in this research. They were randomly allocated to 4 groups as follows: sham group, vehicle group, monascin-treated group, and Glivec-treated group. Animals were euthanized at 3 days after the model was established successfully. We observed the effects of PPAR-γ on the brain water content, hemoglobin levels, and the expressions of CD163 and Hp in Western blot and real-ime PCR; meanwhile, we measured hematoma volumes and edema areas by MRI scanning.

Result: The results showed that PPAR-γ agonist significantly reduced hematoma volume, brain edema, and hemoglobin after ICH. It also enhanced CD163 and Hp expression while PPAR-γ antagonist had the opposite effects.

Conclusions: PPAR-γ promotes hematoma clearance and plays a protective role through the Hp-Hb-CD163 pathway in a rat collagenase infusion ICH model.

MeSH terms

  • Animals
  • Antigens, CD / physiology
  • Antigens, Differentiation, Myelomonocytic / physiology
  • Brain / metabolism
  • Brain Injuries / complications
  • Cerebral Hemorrhage / physiopathology*
  • Disease Models, Animal
  • Haptoglobins / physiology
  • Hematoma / pathology
  • Hemoglobins / physiology
  • Male
  • Neurons / drug effects
  • PPAR gamma / metabolism*
  • PPAR gamma / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / physiology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Haptoglobins
  • Hemoglobins
  • Hp protein, rat
  • PPAR gamma
  • PPAR gamma, rat
  • Receptors, Cell Surface