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 T. Lamb, Richard M. Ransohoff

Research output: Contribution to journalArticle

24 Scopus citations

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)
Pages (from-to)233-242
Number of pages10
JournalBrain, Behavior, and Immunity
Volume54
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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  • Cite this

    Provencio, J. J., Swank, V., Lu, H., Brunet, S., Baltan, S., Khapre, R. V., Seerapu, H., Kokiko-Cochran, O. N., Lamb, B. T., & Ransohoff, R. M. (2016). Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. Brain, Behavior, and Immunity, 54, 233-242. https://doi.org/10.1016/j.bbi.2016.02.007