Curcumin attenuates cerebral edema following traumatic brain injury in mice: A possible role for aquaporin-4?

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1β, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1β-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of nuclear factor κB. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation.

Original languageEnglish (US)
Pages (from-to)637-648
Number of pages12
JournalJournal of Neurochemistry
Volume113
Issue number3
DOIs
StatePublished - May 1 2010

Fingerprint

Aquaporin 4
Curcumin
Brain Edema
Brain
Astrocytes
Interleukin-1
Chemical activation
Aquaporins
Intracranial Hypertension
Glial Fibrillary Acidic Protein
Wounds and Injuries
Craniocerebral Trauma
Neuroglia
Water content
Traumatic Brain Injury
Edema
Cytokines
Morbidity
Mortality
Water

Keywords

  • Cellular edema
  • Controlled cortical impact
  • Glia
  • Intracranial pressure
  • Neuroinflammation
  • Neurotrauma

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

@article{95100ba15fac45c0ad3f22a495110df5,
title = "Curcumin attenuates cerebral edema following traumatic brain injury in mice: A possible role for aquaporin-4?",
abstract = "Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1β, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1β-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of nuclear factor κB. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation.",
keywords = "Cellular edema, Controlled cortical impact, Glia, Intracranial pressure, Neuroinflammation, Neurotrauma",
author = "Laird, {Melissa D.} and Sangeetha Sukumari-Ramesh and Swift, {Andrew E.B.} and Meiler, {Steffen E.} and Vender, {John R.} and Dhandapani, {Krishnan M.}",
year = "2010",
month = "5",
day = "1",
doi = "10.1111/j.1471-4159.2010.06630.x",
language = "English (US)",
volume = "113",
pages = "637--648",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Curcumin attenuates cerebral edema following traumatic brain injury in mice

T2 - A possible role for aquaporin-4?

AU - Laird, Melissa D.

AU - Sukumari-Ramesh, Sangeetha

AU - Swift, Andrew E.B.

AU - Meiler, Steffen E.

AU - Vender, John R.

AU - Dhandapani, Krishnan M.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1β, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1β-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of nuclear factor κB. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation.

AB - Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1β, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1β-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of nuclear factor κB. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation.

KW - Cellular edema

KW - Controlled cortical impact

KW - Glia

KW - Intracranial pressure

KW - Neuroinflammation

KW - Neurotrauma

UR - http://www.scopus.com/inward/record.url?scp=77950634233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950634233&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2010.06630.x

DO - 10.1111/j.1471-4159.2010.06630.x

M3 - Article

C2 - 20132469

AN - SCOPUS:77950634233

VL - 113

SP - 637

EP - 648

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -