Skip to main content
eScholarship
Open Access Publications from the University of California

Clemastine rescues myelination defects and promotes functional recovery in hypoxic brain injury.

  • Author(s): Cree, Bruce AC
  • Niu, Jianqin
  • Hoi, Kimberly K
  • Zhao, Chao
  • Caganap, Scott D
  • Henry, Roland G
  • Dao, Dang Q
  • Zollinger, Daniel R
  • Mei, Feng
  • Shen, Yun-An A
  • Franklin, Robin JM
  • Ullian, Erik M
  • Xiao, Lan
  • Chan, Jonah R
  • Fancy, Stephen PJ
  • et al.
Abstract

Hypoxia can injure brain white matter tracts, comprised of axons and myelinating oligodendrocytes, leading to cerebral palsy in neonates and delayed post-hypoxic leukoencephalopathy (DPHL) in adults. In these conditions, white matter injury can be followed by myelin regeneration, but myelination often fails and is a significant contributor to fixed demyelinated lesions, with ensuing permanent neurological injury. Non-myelinating oligodendrocyte precursor cells are often found in lesions in plentiful numbers, but fail to mature, suggesting oligodendrocyte precursor cell differentiation arrest as a critical contributor to failed myelination in hypoxia. We report a case of an adult patient who developed the rare condition DPHL and made a nearly complete recovery in the setting of treatment with clemastine, a widely available antihistamine that in preclinical models promotes oligodendrocyte precursor cell differentiation. This suggested possible therapeutic benefit in the more clinically prevalent hypoxic injury of newborns, and we demonstrate in murine neonatal hypoxic injury that clemastine dramatically promotes oligodendrocyte precursor cell differentiation, myelination, and improves functional recovery. We show that its effect in hypoxia is oligodendroglial specific via an effect on the M1 muscarinic receptor on oligodendrocyte precursor cells. We propose clemastine as a potential therapy for hypoxic brain injuries associated with white matter injury and oligodendrocyte precursor cell maturation arrest.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View