Hypoxia-ischemia-mediated oligodendroglial cell death and its recovery in the corpus callosum subventricular zone.

Guardia Clausi M., Pasquini LA. and Pasquini JM.

Depto Química Biológica e Instituto de Química y Fisicoquímica Biológica Universidad de Buenos Aires and CONICET Buenos Aires Argentina.

We have previously demonstrated that apotransferrin (aTf) intracranially injected (ICI) in rats at 3 days of age produces an accelerated oligodendroglial cell (OLGc) maturation. In order to investigate if aTf provides neuroprotection to oligodendrocyte precursor cells (OPCs) following cerebral hypoxia-ischemia (H-I), we used a neonatal rat model of white matter damage previously described by Vanucci et al., 2005. Briefly H/I was produced in 7-day-old Wistar rats by a permanent unilateral carotid artery ligation and, after 3 h of recovery, the animals were exposed to 120 min of humidified 8% O2/92% N2. Twenty-four hours after H-I animals were ICI with 350 ng of aTf and effects were evaluated at different time points.

H-I produced severe damage on corpus callosum (CC) Myelination which was accompanied by microglia activation and astrogliosis. Also in the CC and 72 h post ischemia, caspase-3 colocalized with O4+ cells. The ICI of aTf significantly decreased the number of caspase-3+ cells as well as microglia activation and astrogliosis. On the other hand, 3 days after H-I an increased number of nestin and PCNA positive cells were observed in the dorsolateral subventricular zone (SVZ). At the same time and at the same localization, an increase in the number of caspase-3+ cells was observed. When aTf was ICI, an important amount of nestin and PCNa+ cells were observed in a extended area of the SVZ, which was accompanied by a decrease in caspase-3+ cells. It was found that PCNA+ cells co-localized with PDGFRα + cells, suggesting that they were cells in transit to the CC.

Our results suggest that the accelerated oligodendroglial maturation and a concomitant remyelination induced by aTf in the CC diminished the microglial and astroglial activation, which generate an appropriate and more favorable environment for the proliferation and survival of SVZ progenitors and also favor their commitment to oligodendroglial fate.

Acknowledgements: Supported by Agencia Nacional de Ciencia y Tecnología ( BID 1728 OC/AR PICT 38201).