Xiaofeng Jia, MD, MS, PhD, FCCM
Professor
University of Maryland School of Medicine
Baltimore, MD
Disclosure information not submitted.
Songyu Chen, MD, PhD
Dr.
University of Maryland School of Medicine, United States
Disclosure information not submitted.
Zhuoran Wang, MD, MS
Dr.
University of Maryland School of Medicine, United States
Disclosure information not submitted.
Jian Du, PhD
Dr.
University of Maryland School of Medicine, United States
Disclosure information not submitted.
Title: Intranasal Delivery of human NSCs inhibited Inflammatory Astrocytes after Cardiac Arrest in Rats
Introduction: Cardiac arrest (CA) is a common yet devastating disease. The cerebral injury resulted from CA is the key cause of death. How to ameliorate and even reverse this injury remains under the spotlight. Our group has previously reported that intranasal application of human neural stem cells (hNSCs) improves the overall neurological function and reduces the histological injury in a rat asphyxial CA model.
Methods: 16 Wistar rats were randomly assigned to control and hNSCs groups (N = 8/group). After 8 minutes of asphyxial CA, 5*105 of hNSCs were administered intranasally in the treatment groups. Neurological deficit scores (NDS) were assessed at 6, 24, 48, and 72h after return of spontaneous circulation (ROSC). Immunofluorescence was used to track hNSCs and quantitatively evaluate astrocyte survival and related pathways.
Results: The NDS scores in the hNSC group were significantly improved compared to the control group. The sub-analysis of neurological deficit score (NDS), which represents the advanced neurological function, was also improved by the treatment (P< 0.05 at all time points). The numbers of astrocytes marked by Glial fibrillary acidic protein (GFAP) were markedly reduced in CA 2 and dentate gyrus (DG) regions of the hippocampus 72 hours after CA (P< 0.05). Immunofluorescence studies demonstrated that the astrogliosis in the hippocampus was inhibited by hNSCs, possibly through the Toll-like receptor 4 (TLR4)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3) pathways.
Conclusions: Taken together, hNSC therapy significantly improved functional outcomes after CA. The potential neuroprotective mechanism of this non-invasive treatment of human NSCs might be through reducing astrocyte-mediated inflammation.
Supported in part by the NINDS R01NS110387 and NHLBI R01HL118084 (both to X Jia).