Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage

Melanie D. King, Wittstatt A. Whitaker-Lea, James M. Campbell, Cargill Herley Alleyne, Krishnan Michael Dhandapani

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

Original languageEnglish (US)
Article number495817
JournalInternational Journal of Cell Biology
DOIs
StatePublished - Jan 1 2014

Fingerprint

Cerebral Hemorrhage
Wounds and Injuries
Stroke
Collagenases
necrostatin-1
Blood-Brain Barrier
Hematoma
Edema
Cell Death
Therapeutics
Mortality

ASJC Scopus subject areas

  • Cell Biology

Cite this

Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage. / King, Melanie D.; Whitaker-Lea, Wittstatt A.; Campbell, James M.; Alleyne, Cargill Herley; Dhandapani, Krishnan Michael.

In: International Journal of Cell Biology, 01.01.2014.

Research output: Contribution to journalArticle

King, Melanie D. ; Whitaker-Lea, Wittstatt A. ; Campbell, James M. ; Alleyne, Cargill Herley ; Dhandapani, Krishnan Michael. / Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage. In: International Journal of Cell Biology. 2014.
@article{3bb7933988124402b209d96130ad277c,
title = "Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage",
abstract = "Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15{\%} of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54{\%} at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48{\%}, reduced blood-brain barrier opening by 51{\%}, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.",
author = "King, {Melanie D.} and Whitaker-Lea, {Wittstatt A.} and Campbell, {James M.} and Alleyne, {Cargill Herley} and Dhandapani, {Krishnan Michael}",
year = "2014",
month = "1",
day = "1",
doi = "10.1155/2014/495817",
language = "English (US)",
journal = "International Journal of Cell Biology",
issn = "1687-8876",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage

AU - King, Melanie D.

AU - Whitaker-Lea, Wittstatt A.

AU - Campbell, James M.

AU - Alleyne, Cargill Herley

AU - Dhandapani, Krishnan Michael

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

AB - Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

UR - http://www.scopus.com/inward/record.url?scp=84897850099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897850099&partnerID=8YFLogxK

U2 - 10.1155/2014/495817

DO - 10.1155/2014/495817

M3 - Article

JO - International Journal of Cell Biology

JF - International Journal of Cell Biology

SN - 1687-8876

M1 - 495817

ER -