Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

Jose Javier Provencio, Valerie Swank, Haiyan Lu, Sylvain Brunet, Selva Baltan, Rohini V. Khapre, Himabindu Seerapu, Olga N. Kokiko-Cochran, Bruce Lamb, Richard M. Ransohoff

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.

Original languageEnglish (US)
JournalBrain, Behavior, and Immunity
DOIs
StateAccepted/In press - Nov 2 2015
Externally publishedYes

Fingerprint

Subarachnoid Hemorrhage
N-Methyl-D-Aspartate Receptors
Neutrophils
Long-Term Potentiation
Memory Disorders
Inflammation
Executive Function
Middle Cerebral Artery
Vasoconstriction
Innate Immunity
Hemorrhage
Phenotype
Wounds and Injuries

Keywords

  • Cerebral vasospasm
  • Delayed neurological deterioration after subarachnoid hemorrhage
  • Innate inflammation
  • Memory deficits
  • Neutrophils
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Provencio, J. J., Swank, V., Lu, H., Brunet, S., Baltan, S., Khapre, R. V., ... Ransohoff, R. M. (Accepted/In press). Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. Brain, Behavior, and Immunity. https://doi.org/10.1016/j.bbi.2016.02.007

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. / Provencio, Jose Javier; Swank, Valerie; Lu, Haiyan; Brunet, Sylvain; Baltan, Selva; Khapre, Rohini V.; Seerapu, Himabindu; Kokiko-Cochran, Olga N.; Lamb, Bruce; Ransohoff, Richard M.

In: Brain, Behavior, and Immunity, 02.11.2015.

Research output: Contribution to journalArticle

Provencio, JJ, Swank, V, Lu, H, Brunet, S, Baltan, S, Khapre, RV, Seerapu, H, Kokiko-Cochran, ON, Lamb, B & Ransohoff, RM 2015, 'Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors', Brain, Behavior, and Immunity. https://doi.org/10.1016/j.bbi.2016.02.007
Provencio, Jose Javier ; Swank, Valerie ; Lu, Haiyan ; Brunet, Sylvain ; Baltan, Selva ; Khapre, Rohini V. ; Seerapu, Himabindu ; Kokiko-Cochran, Olga N. ; Lamb, Bruce ; Ransohoff, Richard M. / Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. In: Brain, Behavior, and Immunity. 2015.
@article{32dd273381d041ee8fc909076301d2a7,
title = "Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors",
abstract = "Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.",
keywords = "Cerebral vasospasm, Delayed neurological deterioration after subarachnoid hemorrhage, Innate inflammation, Memory deficits, Neutrophils, Subarachnoid hemorrhage",
author = "Provencio, {Jose Javier} and Valerie Swank and Haiyan Lu and Sylvain Brunet and Selva Baltan and Khapre, {Rohini V.} and Himabindu Seerapu and Kokiko-Cochran, {Olga N.} and Bruce Lamb and Ransohoff, {Richard M.}",
year = "2015",
month = "11",
day = "2",
doi = "10.1016/j.bbi.2016.02.007",
language = "English (US)",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

AU - Provencio, Jose Javier

AU - Swank, Valerie

AU - Lu, Haiyan

AU - Brunet, Sylvain

AU - Baltan, Selva

AU - Khapre, Rohini V.

AU - Seerapu, Himabindu

AU - Kokiko-Cochran, Olga N.

AU - Lamb, Bruce

AU - Ransohoff, Richard M.

PY - 2015/11/2

Y1 - 2015/11/2

N2 - Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.

AB - Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.

KW - Cerebral vasospasm

KW - Delayed neurological deterioration after subarachnoid hemorrhage

KW - Innate inflammation

KW - Memory deficits

KW - Neutrophils

KW - Subarachnoid hemorrhage

UR - http://www.scopus.com/inward/record.url?scp=84964335880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964335880&partnerID=8YFLogxK

U2 - 10.1016/j.bbi.2016.02.007

DO - 10.1016/j.bbi.2016.02.007

M3 - Article

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

ER -