The Proliferation Capacity of Cultured Neural Stem Cells Promoted by CSF Collected from SAH Patients Correlates to Clinical Outcome

Yun-An Chen,Tai-Horng Young,Li-Kai Tsai,Kuo-Chuan Wang,Der-Zen Liu

doi:10.1038/s41598-018-19371-5

Abstract

Neurogenesis from endogenous neural stem cells (NSCs) might contribute to functional recovery after stroke based on animal studies; however, the relationship between neurogenesis and post-stroke outcome has rarely been demonstrated in humans. We prospectively collected cerebrospinal fluid (CSF) from 36 patients with subarachnoid hemorrhage (SAH). The CSF was added to the culture medium of the rat NSCs to test the effects on proliferation (proliferation index [PI], percentage of Ki-67 immunoreactive cells). We correlated the PI with functional outcome based on the modified Rankin Scale at 3 months post-SAH. Treatment with the CSF samples collected from SAH patients showed a higher PI compared with those collected from patients with normal pressure hydrocephalus and untreated controls (20.3 ± 8.8 vs. 8.2 ± 5.1 and 7.8 ± 3.0, P < 0.001), indicating proliferation-promoting factors in CSF after SAH. The PI was positively correlated with SAH volume (p = 0.025). For patients with lower SAH volume, patients with favorable outcome had a higher PI than those with poor outcome (20.8 ± 6.9 vs. 14.6 ± 4.3, p = 0.047). Using multivariable logistic regression analysis, the PI was a positive determinant for favorable outcome (odds ratio, 1.17; 95% confidence interval, 1.00 to 1.36) that more proliferation-promoting factors in CSF was associated with better functional outcome in SAH patients.

Highlights

Relationship between neurogenesis and subarachnoid hemorrhage (SAH) provides a chance to delineate the pathogenesis of the disease, and to develop a potential treatment strategy, especially since there is still no effective therapy for SAH patients[14]
We showed that the proliferation capacity of cultured neural stem cells (NSCs) promoted by cerebrospinal fluid (CSF) collected from SAH patients correlates well with disease severity and functional outcome
The CSF was added to the culture medium of NSCs, which was obtained from rat embyronic day 15 (E15) fetal brain

Summary

Introduction

Relationship between neurogenesis and SAH provides a chance to delineate the pathogenesis of the disease, and to develop a potential treatment strategy, especially since there is still no effective therapy for SAH patients[14]. In pathological conditions, injured brain may release some factors that diffuse to the SVZ and SGZ regions and stimulate neurogenesis[15]. We have demonstrated that the NSC proliferation capacity is increased at the SVZ regions in a rat model of SAH at post-SAH 5–7 days[11]. The CSF collected from SAH rats during post-SAH 5–7 days can enhance the proliferating potentials of cultured rodent NSCs11. These findings imply the existence of proliferation-promoting factors in CSF of SAH rats. We showed that the proliferation capacity of cultured NSCs promoted by CSF collected from SAH patients correlates well with disease severity and functional outcome

Methods

Results

Conclusion