科研之友
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摘要
Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DR alpha 1 domain linked covalently to mouse (m)MOG-35-55 peptide (DR alpha 1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke. The aim of the current study was to determine if DR alpha 1-MOG-35-55 treatment of a fluid percussion injury (FPI) mouse model of TBI could reduce the lesion size and improve disease outcome measures. Neurodeficits, lesion size, and immune responses were determined to evaluate the therapeutic potential and mechanisms of neuroprotection induced by DR alpha 1-MOG-35-55 treatment. The results demonstrated that daily injections of DR alpha 1-MOG-35-55 given after FPI significantly reduced numbers of infiltrating CD74(+) and CD86(+) macrophages and increased numbers of CD206(+) microglia in the brain concomitant with smaller lesion sizes and improvement in neurodeficits. Conversely, DR alpha 1-MOG-35-55 treatment of TBI increased numbers of circulating CD11b(+) monocytes and their expression of CD74 but had no detectable effect on cell numbers or marker expression in the spleen. These results demonstrate that DR alpha 1-MOG-35-55 therapy can reduce CNS inflammation and significantly improve histological and clinical outcomes after TBI. Future studies will further examine the potential of DR alpha 1-MOG-35-55 for treatment of TBI.
