Research paperDevelopmental neuroscienceMinocycline alleviates hypoxic–ischemic injury to developing oligodendrocytes in the neonatal rat brain
Section snippets
Chemicals
Unless otherwise stated, all chemicals used in this study were purchased from Sigma (St. Louis, MO, USA). Monoclonal mouse antibodies against O4, O1, glial fibrillary acidic protein (GFAP), neuron-specific nuclear protein (NeuN) or nitrotyrosine (NT), rabbit anti-caspase-3 (the active form) antibody, and the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining kit were purchased from Chemicon (Temecula, CA, USA). Mouse anti-myelin
Minocycline attenuated HI-induced brain injury
BCAO followed by 15 min hypoxic exposure resulted in cell death, as indicated by many pyknotic cells shown by the Nissl staining, in the cingulum, the subventricular areas and the subcortical white matter tract of 82% of the rat brain 24 h after the HI insult (Fig. 1B and Table 1). In some more severely injured brains, pyknotic cells were not limited to the white matter area and they were also found in the adjacent cortical gray matter. No pyknotic cells were found in the SH rat brain (Fig. 1A)
Discussion
The protective effect of doxycycline, a similar tetracycline compound as minocycline, on ischemic brain injury was first found in rabbits (Clark et al., 1994). Minocycline was later reported to protect the adult gerbil brain from injury induced by global ischemia (Yrjanheikki et al., 1998) and the adult rat brain from focal ischemic injury (Xu et al 2004, Yrjanheikki et al 1999). Minocycline has also been found to markedly protect the neonatal rat brain against HI injury (Arvin et al., 2002).
Conclusion
In summary, we showed that minocycline attenuates HI-induced injury to developing OLs and hypomyelination in the neonatal rat brain. The protective effect of minocycline in the present study is associated with its ability to reduce microglial activation.
Acknowledgment
This work was supported by HD 35496 and NS 54278.
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