Activation of Cytotoxic Natural Killer Cells After Aneurysmal Subarachnoid Hemorrhage

Daniel Spitzer, Nina J Spitzer, Monika Deininger, Christian R Wirtz, Ralph König, Timo Burster, Thomas Kapapa

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


OBJECTIVE: Cell-mediated inflammation is critical in the development of cerebrovascular complications after aneurysmal subarachnoid hemorrhage. We analyzed the course for activated CD16brightCD56dim cytotoxic natural killer (NK) cells in cerebrospinal fluid of 15 patients.

METHODS: Patients were classified by occurrence of cerebral vasospasm (CV) and delayed cerebral ischemia. NK were monitored by flow cytometry between day 1 and 14 after hemorrhage.

RESULTS: Twelve patients (80%) developed CV with a mean day of detection at 3.9 ± 1.6. In those patients, cell count for NK increased from 1.40 ± 1.42 cells/μL on day 1 to a peak of 11.66 ± 11.56 cells/μL on day 6.1 ± 2.9 (P = 0.001). An increase of mean cerebral blood flow velocity in transcranial Doppler from 71.33 ± 12.93 cm/second to 166.20 ± 20.19 cm/second (P < 0.01) and an increase in number of vascular axes affected by CV was detected (P < 0.01). In patients with grade 3 CV (n = 4, 33.3%), activated NK counts were significantly higher than in patients who did not have CV (23.18 ± 13.92 cells/μL vs. 0.02 ± 0.01 cells/μL; P = 0.029). NK counts were significantly different between patients with grade 1 and grade 3 CV (P = 0.04). Patients who did not have CV who showed low NK counts achieved better functional outcome (Glasgow Outcome Scale [GOS] score, 4.6 ± 0.6) at discharge than did patients with CV grade 2 (GOS score, 3.3 ± 0.5) and CV grade 3 (GOS score, 2.3 ± 0.5) who showed increased NK cell counts (CV grade 0 vs. CV grade 2, P = 0.048; CV grade 0 vs. CV grade 3, P = 0.001). Activated CD16brightCD56dim cytotoxic NKCSF cell counts showed a mean maximum (14.15 ± 12.21 cells/μL) when delayed cerebral ischemia occurred.

CONCLUSIONS: The increase of activated CD16brightCD56dim cytotoxic NK cells in cerebrospinal fluid after aneurysmal subarachnoid hemorrhage suggests an increased risk of CV and delayed cerebral ischemia.

Original languageEnglish
Pages (from-to)666-676.e1
JournalWorld Neurosurgery
Publication statusPublished - May 2017
Externally publishedYes


  • Adult
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Killer Cells, Natural
  • Male
  • Middle Aged
  • Prospective Studies
  • Subarachnoid Hemorrhage
  • Vasospasm, Intracranial
  • Journal Article
  • Observational Study

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