Activation of Cytotoxic Natural Killer Cells After Aneurysmal Subarachnoid Hemorrhage.
OBJECTIVE
Cell-mediated inflammation is critical in the development of cerebrovascular complications after aneurysmal subarachnoid hemorrhage. We analyzed the course for activated CD16brightCD56dimcytotoxic 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 CD16brightCD56dimcytotoxic NKCSFcell counts showed a mean maximum (14.15 ± 12.21 cells/μL) when delayed cerebral ischemia occurred.


CONCLUSIONS
The increase of activated CD16brightCD56dimcytotoxic NK cells in cerebrospinal fluid after aneurysmal subarachnoid hemorrhage suggests an increased risk of CV and delayed cerebral ischemia.
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Daniel
D
Spitzer
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Nina J
NJ
Spitzer
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Monika
M
Deininger
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Christian R
CR
Wirtz
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Ralph
R
König
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Timo
T
Burster
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany. Electronic address: Thomas.Kapapa@uniklinkik-ulm.de.
Thomas
T
Kapapa
D000328:Adult; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000276:immunology / Q000378:metabolism*; D020301:Vasospasm, Intracranial / Q000276:immunology / Q000378:metabolism*
Angiography; Delayed cerebral ischemia; Infarction; Inflammation; Outcome