Stanniocalcin-1 ameliorates cerebral ischemia by decrease oxidative stress and blood brain barrier permeability

Microvasc Res. 2020 Mar:128:103956. doi: 10.1016/j.mvr.2019.103956. Epub 2019 Nov 13.

Abstract

Blood brain barrier (BBB) permeability and oxidative stress have been reported to be important mechanisms for brain damage following ischemic stroke and stanniocalcin-1 (STC-1), a neuroprotective protein, has anti-inflammatory and anti-oxidative stress properties. Herein, we report the effect of STC-1 on BBB permeability and brain oxidative stress after stroke in an animal model. Male Wistar received an intracerebroventricularly injection of human recombinant STC-1 (100 ng/kg) or saline and were subjected to sham procedure or global cerebral ischemia/reperfusion (I/R) model. Six and 24 h after I/R, neurological evaluation was performed; at 24 h brain water content was evaluated in the total brain, and BBB permeability, nitrite/nitrate (N/N) concentration, lipid peroxidation, protein carbonyls formation, superoxide dismutase (SOD) and catalase (CAT) activity were determined in the hippocampus, cortex, prefrontal cortex, striatum and cerebellum. Rats exhibited neurological deficit at 6 and 24 h after I/R and STC-1 reduction at 24 h. After I/R there were an increase of brain water content, BBB permeability in the hippocampus, cortex and pre-frontal cortex and N/N in the hippocampus, and STC-1 decreased this level only in the hippocampus. STC-1 decreased lipid peroxidation in the hippocampus, cortex and prefrontal cortex and protein oxidative damage in the hippocampus and cortex. SOD activity decreased in the hippocampus, cortex and prefrontal cortex after I/R and STC-1 reestablished these levels in the hippocampus and cortex. CAT activity decreased only in the hippocampus and cortex and STC-1 increased the CAT activity in the hippocampus. Our data provide the first experimental demonstration that STC-1 reduced brain dysfunction associated with cerebral I/R in rats, by decreasing BBB permeability and oxidative stress parameters.

Keywords: Blood brain barrier; Oxidative stress; Stanniocalcin-1; Stroke.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / physiopathology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Edema / metabolism
  • Brain Edema / physiopathology
  • Brain Edema / prevention & control
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Brain Ischemia / prevention & control*
  • Capillary Permeability / drug effects*
  • Disease Models, Animal
  • Glycoproteins / administration & dosage*
  • Injections, Intraventricular
  • Lipid Peroxidation / drug effects
  • Male
  • Neuroprotective Agents / administration & dosage*
  • Oxidative Stress / drug effects*
  • Protein Carbonylation / drug effects
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction

Substances

  • Antioxidants
  • Glycoproteins
  • Neuroprotective Agents
  • teleocalcin