Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice

Michela Campolo, Emanuela Esposito, Akbar Ahmad, Rosanna Di Paola, Irene Paterniti, Marika Cordaro, Giuseppe Bruschetta, John L. Wallace, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Traumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury. Methods: Here we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 μmol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days. Results: Results revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI. Conclusions: These data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process.

Original languageEnglish (US)
Article number196
JournalJournal of Neuroinflammation
Volume11
Issue number1
DOIs
StatePublished - Dec 4 2014
Externally publishedYes

Fingerprint

Hydrogen Sulfide
Cyclooxygenase Inhibitors
Naproxen
Wounds and Injuries
Inflammation
Animal Models
2-(6-methoxy-napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester
Traumatic Brain Injury
Carboxymethylcellulose Sodium
Central Nervous System Diseases
Recovery of Function
Brain Edema
Nerve Growth Factors
Dimethyl Sulfoxide
Spinal Cord Injuries
Neuroglia
Suspensions
Esters
Cell Death
Theoretical Models

Keywords

  • Astrogliosis
  • Brain trauma
  • Hydrogen sulfide
  • Infarct area
  • Infarct volume
  • Inflammation
  • Motor recovery
  • Neuroprotection
  • Neurotrophic factor
  • Nitrosative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology

Cite this

Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice. / Campolo, Michela; Esposito, Emanuela; Ahmad, Akbar; Di Paola, Rosanna; Paterniti, Irene; Cordaro, Marika; Bruschetta, Giuseppe; Wallace, John L.; Cuzzocrea, Salvatore.

In: Journal of Neuroinflammation, Vol. 11, No. 1, 196, 04.12.2014.

Research output: Contribution to journalArticle

Campolo, Michela ; Esposito, Emanuela ; Ahmad, Akbar ; Di Paola, Rosanna ; Paterniti, Irene ; Cordaro, Marika ; Bruschetta, Giuseppe ; Wallace, John L. ; Cuzzocrea, Salvatore. / Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice. In: Journal of Neuroinflammation. 2014 ; Vol. 11, No. 1.
@article{ddaeb6b67c074819b576b50df35651bf,
title = "Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice",
abstract = "Background: Traumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury. Methods: Here we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 μmol/kg) or vehicle (dimethylsulfoxide:1{\%} carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days. Results: Results revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI. Conclusions: These data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process.",
keywords = "Astrogliosis, Brain trauma, Hydrogen sulfide, Infarct area, Infarct volume, Inflammation, Motor recovery, Neuroprotection, Neurotrophic factor, Nitrosative stress",
author = "Michela Campolo and Emanuela Esposito and Akbar Ahmad and {Di Paola}, Rosanna and Irene Paterniti and Marika Cordaro and Giuseppe Bruschetta and Wallace, {John L.} and Salvatore Cuzzocrea",
year = "2014",
month = "12",
day = "4",
doi = "10.1186/s12974-014-0196-1",
language = "English (US)",
volume = "11",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice

AU - Campolo, Michela

AU - Esposito, Emanuela

AU - Ahmad, Akbar

AU - Di Paola, Rosanna

AU - Paterniti, Irene

AU - Cordaro, Marika

AU - Bruschetta, Giuseppe

AU - Wallace, John L.

AU - Cuzzocrea, Salvatore

PY - 2014/12/4

Y1 - 2014/12/4

N2 - Background: Traumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury. Methods: Here we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 μmol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days. Results: Results revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI. Conclusions: These data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process.

AB - Background: Traumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury. Methods: Here we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 μmol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days. Results: Results revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI. Conclusions: These data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process.

KW - Astrogliosis

KW - Brain trauma

KW - Hydrogen sulfide

KW - Infarct area

KW - Infarct volume

KW - Inflammation

KW - Motor recovery

KW - Neuroprotection

KW - Neurotrophic factor

KW - Nitrosative stress

UR - http://www.scopus.com/inward/record.url?scp=84924902386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924902386&partnerID=8YFLogxK

U2 - 10.1186/s12974-014-0196-1

DO - 10.1186/s12974-014-0196-1

M3 - Article

C2 - 25472548

AN - SCOPUS:84924902386

VL - 11

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

IS - 1

M1 - 196

ER -