29
PLoS One. 2012;7(6):e39500.
Mesenchymal stem cell graft
improves
recovery after spinal cord injury in adult rats through
neurotrophic and pro-angiogenic actions.
Quertainmont R, Cantinieaux D, Botman O, Sid S, Schoenen J, Franzen R.
Abstract
Numerous strategies have been managed to improve functional recovery after spinal cord
injury (SCI) but an optimal strategy doesn’t exist yet. Actually, it is the complexity of the
injured spinal cord pathophysiology that begets the multifactorial approaches assessed to
favour tissue protection, axonal regrowth and functional recovery. In this context, it appears
that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to
graft MSCs after a spinal cord compression injury in adult rat to assess their efect on func-
tional recovery and to highlight their mechanisms of action. We found that in intravenously
grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their
open feld and grid navigation scores compared to control animals. At the histological analysis
of their dissected spinal cord, no MSCs were found within the host despite their BrdU label-
ling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a
cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a signifcant
increase of NGF expression in the injured tissue. Also, a signifcant tissue sparing efect of MSC
graft was observed. Finally, we also show that MSCs promote vascularisation, as the density
of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring
here some new evidences that MSCs most likely act throughout their secretions and not via
their own integration/diferentiation within the host tissue.
Hum Mol Genet. 2012 Dec 1;21(23):5106-17.
Mutations of EFHC1, linked to juvenile myoclonic
epilepsy, disrupt radial and tangential migrations
during brain development.
de Nijs L, Wolkof N, Coumans B, Delgado-Escueta AV, Grisar T, Lakaye B.
Abstract
Heterozygous mutations in Myoclonin1/EFHC1 cause juvenile myoclonic epilepsy (JME), the
most common form of genetic generalized epilepsies, while homozygous F229L mutation is
associated with primary intractable epilepsy in infancy. Heterozygous mutations in adolescent
JME patients produce subtle malformations of cortical and subcortical architecture, whereas
homozygous F229L mutation in infancy induces severe brain pathology and death. However,
the underlying pathological mechanisms for these observations remain unknown. We had pre-
viously demonstrated that EFHC1 is a microtubule-associated protein (MAP) involved in cell
division and radial migration during cerebral corticogenesis. Here, we show that JME muta-
tions, including F229L, do not alter the ability of EFHC1 to colocalize with the centrosome
and the mitotic spindle, but act in a dominant-negative manner to impair mitotic spindle orga-
nization. We also found that mutants EFHC1 expression disrupted radial and tangential migra-
tion by afecting the morphology of radial glia and migrating neurons. These results show how
Myoclonin1/EFHC1 mutations disrupt brain development and potentially produce structural
brain abnormalities on which epileptogenesis is established.