Systemic administration of dendrimer N‐acetyl cysteine improves outcomes and survival following cardiac arrest
Abstract
Cardiac arrest (CA), the sudden cessation of effective cardiac pumping function, is still a major clinical problem with a high rate of early and long‐term mortality. Post‐cardiac arrest syndrome (PCAS) may be related to an early systemic inflammatory response leading to exaggerated and sustained neuroinflammation. Therefore, early intervention with targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes. Using a clinically relevant asphyxia CA model, we demonstrate that a single (i.p.) dose of dendrimer‐N‐acetylcysteine conjugate (D‐NAC), can target “activated” microglial cells following CA, leading to an improvement in post‐CA survival rate compared to saline (86% vs. 45%). D‐NAC treatment also significantly improved gross neurological score within 4 h of treatment (p p p p < 0.001). These results demonstrate that early therapeutic intervention even with a single D‐NAC bolus results in a robust sustainable improvement in long‐term survival, short‐term motor deficits, and neurological recovery. Our current work lays the groundwork for a clinically relevant therapeutic approach to treating post‐CA syndrome.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 13, 2021
- Source ID
- 10.1002/btm2.10259
Entities
People
- Elizabeth S. Khoury
- Hiren R Modi
- Nirnath Sah
- Nitish Thakor
- Payam Gharibani
- Qihong Wang
- Rangaramanujam M Kannan
- Rishi Sharma
- Sarah J. Olmstead
- Sujatha Kannan
- Yu Guo
Organizations
- Johns Hopkins University
- National Heart, Lung, and Blood Institute
- University of Maryland School of Medicine