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

UCLA

UCLA Previously Published Works bannerUCLA

White matter loss in a mouse model of periventricular leukomalacia is rescued by trophic factors.

  • Author(s): Espinosa-Jeffrey, Araceli
  • Barajas, Socorro AR
  • Arrazola, Alfonso R
  • Taniguchi, Alana
  • Zhao, Paul M
  • Bokhoor, Payam
  • Holley, Sandra M
  • Dejarme, Don P
  • Chu, Brian
  • Cepeda, Carlos
  • Levine, Michael S
  • Gressens, Pierre
  • Feria-Velasco, Alfredo
  • de Vellis, Jean
  • et al.
Abstract

Periventricular leukomalacia (PVL) is the most frequent cause of cerebral palsy and other intellectual disabilities, and currently there is no treatment. In PVL, glutamate excitotoxicity (GME) leads to abnormal oligodendrocytes (OLs), myelin deficiency, and ventriculomegaly. We have previously identified that the combination of transferrin and insulin growth factors (TSC1) promotes endogenous OL regeneration and remyelination in the postnatal and adult rodent brain. Here, we produced a periventricular white matter lesion with a single intracerebral injection of N-methyl-d-aspartate (NMDA). Comparing lesions produced by NMDA alone and those produced by NMDA + TSC1 we found that: NMDA affected survival and reduced migration of OL progenitors (OLPs). In contrast, mice injected with NMDA + TSC1 proliferated twice as much indicating that TSC1 supported regeneration of the OLP population after the insult. Olig2-mRNA expression showed 52% OLP survival in mice receiving a NMDA injection and increased to 78% when TSC1 + NMDA were injected simultaneously and ventricular size was reduced by TSC1. Furthermore, in striatal slices TSC1 reduced the inward currents induced by NMDA in medium-sized spiny neurons, demonstrating neuroprotection. Thus, white matter loss after excitotoxicity can be partially rescued as TSC1 conferred neuroprotection to preexisting OLP and regeneration via OLP proliferation. Furthermore, we showed that early TSC1 administration maximizes neuroprotection.

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