DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury

Liu Yang, Zhijia Liu, Honglei Ren, Lei Zhang, Siman Gao, Li Ren, Zhi Chai, Roberto Meza-Romero, Gil Benedek, Arthur Vandenbark, Halina Offner, Minshu Li

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-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 DRα1-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 DRα1-MOG-35-55 treatment. The results demonstrated that daily injections of DRα1-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, DRα1-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 DRα1-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 DRα1-MOG-35-55 for treatment of TBI.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMetabolic Brain Disease
DOIs
StateAccepted/In press - Mar 16 2017

Fingerprint

Brain
Percussion
Therapeutics
Inflammation
Wounds and Injuries
Fluids
Traumatic Brain Injury
Macrophages
Microglia
HLA Antigens
Brain Injuries
Multiple Sclerosis
Monocytes
Animals
Spleen
Animal Models
Cell Count
Stroke
Outcome Assessment (Health Care)
Tissue

Keywords

  • CD74
  • DRα1-MOG-35-55 therapy
  • Infiltrating macrophages/microglia
  • Neurological deficits
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury. / Yang, Liu; Liu, Zhijia; Ren, Honglei; Zhang, Lei; Gao, Siman; Ren, Li; Chai, Zhi; Meza-Romero, Roberto; Benedek, Gil; Vandenbark, Arthur; Offner, Halina; Li, Minshu.

In: Metabolic Brain Disease, 16.03.2017, p. 1-8.

Research output: Contribution to journalArticle

Yang, Liu ; Liu, Zhijia ; Ren, Honglei ; Zhang, Lei ; Gao, Siman ; Ren, Li ; Chai, Zhi ; Meza-Romero, Roberto ; Benedek, Gil ; Vandenbark, Arthur ; Offner, Halina ; Li, Minshu. / DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury. In: Metabolic Brain Disease. 2017 ; pp. 1-8.
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