Innovative Immune Therapy Boosts Neurogenesis and Improve Recovery After Traumatic Brain Injury
Saef Izzy1, Taha Yahya2, Michael Aronchik2, Howard Weiner3
1Neurology, Brigham and Women'S Hospital, Harvard Medical School, 2Brigham and Women's Hospital, 3Brigham and Women'S Hospital
Objective:
Develop novel strategies to enhance neurogenesis and modulate immune responses, improving recovery outcomes after traumatic brain injury.
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.
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.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.