Neuronal inflammation induced in a leukomalacia model disrupts the development of myelin cells

Written on Wednesday 23 July 2014

Periventricular leukomalacia is a major cause of cerebral palsy in premature babies. One of the characteristics of this disease is the activation of microglial cells, the cells of the central nervous system implicated in its immune defence.  The occurrence of this inflammatory process in premature infants has long-term consequences on the maturation of the cells that synthesize myelin, known as oligodendrocytes, and is accompanied by a deficit in myelin and in the factors controling this process.

The study was carried out on mice whose carotid artery had been ligated at the age of five days and which represent the animal model of periventricular leukomalacia. The maturation of oligodendrocytes in a mouse of this age is the equivalent to that in a 6 or 7 month old human fœtus. The ligation of the artery provokes an ischemia, i.e. a halt in blood circulation leading to a cell deprivation in oxygen and their death. It is accompanied by a reduction in the myelin thickness around the nerves, in the number of mature oligodendrocytes and in nerve injuries.

Ischemia causes a localized inflammatory response, with activation of microglial cells, but also an increased expression of pro-inflammatory molecules and a transitory reduction in the number of cells that give rise to oligodendrocytes. An increase in the proportion of immature oligodendrocytes is observed. Their migration is also more pronounced. These changes are correlated topographically to the presence of activated microglial cells.

This study highlights an association between the observed inflammatory response and the damage to oligodendrocytes. Future studies modulating neuroinflammation in this experimental model will perhaps allow a better understanding of the interaction between microglial cells and those giving rise to oligodendrocytes, opening up treatment perspectives.

Disease: Periventricular leukomalacia
Experimental model: Mouse, the animal model of periventricular leukomalacia
Study type: Pathophysiology
Laboratory: Dr. Ali Fatemi, Kennedy Krieger Institute, Baltimore (MD), USA

Source : S. Falahati, M. Breu, A.T. Waickman, A.W. Phillips, E.J. Arauz, S. Snyder, M. Porambo, K. Goeral, A.M. Comi, M.A. Wilson, M.V. Johnston, A. Fatemi. Ischemia-induced neuroinflammation is associated with disrupted development of oligodendrocyte progenitors in a model of periventricular leukomalacia. Dev. Neurosci. 2013, 35(2-3):182-96.

Scientific information provided in collaboration with the INIST-CNRS Institute, Institute for Scientific and Technical Information