Abstract Details

Title Innovative Immune Therapy Boosts Neurogenesis and Improve Recovery After Traumatic Brain Injury

Topic Neuro Trauma and Critical Care

Presentation(s) S17 - Neurocritical Care (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

Background

Traumatic brain injury (TBI) causes severe cognitive deficits and neurodegenerative risks, with no effective treatments currently available. Emerging studies suggest that TBI can stimulate neurogenesis, though strategies to enhance this process are limited. In this work, we hypothesized that nasal anti-CD3 therapy modulates neuroinflammation via regulatory T cells, improving functional recovery and potentially promoting neurogenesis in the acute and subacute phases following TBI.

Objective Develop novel strategies to enhance neurogenesis and modulate immune responses, improving recovery outcomes after traumatic brain injury.

Design/Methods We performed controlled cortical impact (CCI) traumatic brain injury in adult C57BL/6J mice and analyzed the effects of nasal aCD3 on neurogenesis and immune modulation in a murine TBI model in vitro and in vivo using behavioral testing, immunohistochemistry, RT-qPCR, and flow cytometry studies.

Results Flow cytometry after TBI revealed decreased Ki67 expression, indicating reduced inflammatory cell proliferation, and increased CD133, marking early neural progenitor activation. Elevated Sox2 and PSA-NCAM at 7 days post-TBI showed enhanced stem cell activity, while histology confirmed increased neurogenesis through DCX+BrdU+ cells at 7 and 14 days post-injury. Nasal anti-CD3 treatment induced regulatory T cells which promoted neural progenitor activity, evidenced by increased Nestin expression in Tregs co-cultured with neurospheres. Treg depletion via diphtheria toxin in DEREG mice reduced neurogenesis at the acute and subacute time points, highlighting Tregs' critical role in the neurogenic effects of nasal anti-CD3 following TBI.

Conclusions Treg plays a critical role in neurogenesis at acute and subacute phase following TBI. Understanding Treg- neuronal progenitor cells direct and indirect communications after injury could reveal new therapeutic targets for TBI and other acute neurological diseases. Nasal anti-CD3 represents a promising therapeutic strategy to treating TBI patients, as it regulates immune responses and enhances neurogenesis following injury.

Authors/Disclosures
Saef Izzy, MD, FAAN (Brigham and Women'S Hospital, Harvard Medical School) PRESENTER	The institution of Dr. Izzy has received research support from NINDS. The institution of Dr. Izzy has received research support from The Gillian Reny Stepping Strong Center for Trauma Innovation. Dr. Izzy has received publishing royalties from a publication relating to health care.
Taha Yahya	Taha Yahya has nothing to disclose.
Michael Aronchik	Michael Aronchik has nothing to disclose.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

��ɫ��

��ɫ��