Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model

Cell Mol Neurobiol. 2015 Mar;35(2):147-57. doi: 10.1007/s10571-014-0106-1. Epub 2014 Sep 2.

Abstract

Carnosine (β-alanyl-L-histidine) has been demonstrated to provide antioxidative and anti-apoptotic roles in the animal of ischemic brain injuries and neurodegenerative diseases. The aim of this study was to examine whether carnosine prevents subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) in rats. We found that intraperitoneal administration of carnosine improved neurobehavioral deficits, attenuated brain edema and blood-brain barrier permeability, and decreased reactive oxygen species level at 48 h following SAH in rat models. Carnosine treatment increased tissue copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) enzymatic activities, and reduced post-SAH elevated lactate dehydrogenase (LDH) activity, the concentration of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHDG), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in rats. Furthermore, carnosine treatment attenuated SAH-induced microglia activation and cortical neuron apoptosis. These results indicated that administration of carnosine may provide neuroprotection in EBI following SAH in rat models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis* / drug effects
  • Behavior, Animal
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology
  • Brain Edema / complications
  • Brain Edema / drug therapy
  • Brain Edema / pathology
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Carnosine / pharmacology
  • Carnosine / therapeutic use*
  • Caspase 3 / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology
  • Cytokines / metabolism
  • DNA / metabolism
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Glutathione Peroxidase / metabolism
  • In Situ Nick-End Labeling
  • Lipids / chemistry
  • Male
  • Microglia / drug effects
  • Microglia / pathology
  • Nerve Tissue Proteins / metabolism
  • Oxidation-Reduction / drug effects
  • Permeability / drug effects
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / pathology
  • Superoxide Dismutase / metabolism

Substances

  • Antigens, Nuclear
  • Antioxidants
  • Cytokines
  • Lipids
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Reactive Oxygen Species
  • Carnosine
  • DNA
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Caspase 3