Validation of the Treatment Outcomes of a Fixed-Dose Combination Therapeutic in a High-Fidelity Porcine Model of Traumatic Brain Injury
Abstract
Traumatic Brain Injury (TBI) is a multi-system disorder involving complex interactions between the brain and immune system. As such, mitigation of inflammation is a cornerstone of TBI treatment. Normally, microglia in the injured brain can produce anti-inflammatory mediators by scavenging cellular debris and orchestrating neurorestorative processes to promote post-TBI neurological recovery. However, microglia can become dysregulated and produce excessive proinflammatory mediators ,which exacerbate brain damage by impeding brain repair and neurological functional recovery. Persistent neuroinflammation in TBI patients may contribute to progressive and long-lasting impairment to their physical, cognitive, behavioral, and social performance. Anti-inflammatory cytokines or interventions can counteract and downregulate these inflammatory and cytotoxic reactions. As one example, acute or delayed treatment with the partial anti-inflammatory medicine anatabine in a mouse TBI model improved long-term spatial memory and reduced pathology at later time points. A recent clinical case study (Dr. Chandler May, MD, JD, MS, FCLM) demonstrated the potential efficacy of levocetirizine (Xyzal ), a well-established FDA-approved anti inflammatory drug a highly selective H1 receptor antagonist (antihistamine), in synergy with the leukotriene receptor antagonist montelukast (Singulair ) in improving TBI outcomes. Thus, early treatment to control inflammation may reduce secondary injury cascades and improve recovery/prognosis. The development of TBI therapies has been challenged by the heterogeneity of TBI and inadequate modeling. To date, single-target anti-inflammatory therapeutics have failed to improve TBI outcomes in numerous clinical trials.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1219050
Entities
People
- Bruce C May
Organizations
- Children's Hospital of Philadelphia
- University of Iowa