Some antibiotics are suggested to exert neuroprotective effects via regulation 
of glial responses. Attenuation of microglial activation by minocycline prevents 
neuronal death in a variety of experimental models for neurological diseases, 
such as cerebral ischemia, Parkinson's and Huntington's disease. Ceftriaxone 
delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis 
through upregulation of astrocytic glutamate transporter expression (GLT-1). 
However, it remains largely unknown whether these antibiotics are able to 
protect neurons in axotomy models for progressive motor neuron diseases. Recent 
studies have shown that the axotomized motoneurons of the adult rat can survive, 
whereas those of the adult mouse undergo neuronal degeneration. We thus examined 
the possible effects of ceftriaxone and minocycline on neuronal loss and glial 
reactions in the mouse hypoglossal nucleus after axotomy. The survival rate of 
lesioned motoneurons at 28 days after axotomy (D28) was significantly improved 
by ceftriaxone and minocycline treatment. There were no significant differences 
in the cellular densities of astrocytes between ceftriaxone-treated and 
saline-treated animals. Ceftriaxone administration increased the expression of 
GLT-1 in the hypoglossal nucleus, while it suppressed the reactive increase of 
glial fibrillary acidic protein (GFAP) expression to control level. The cellular 
densities of microglia at D28 were significantly lower in minocycline-treated 
mice than in saline-treated mice. The time course analysis showed that immediate 
increase in microglia at D3 and D7 was not suppressed by minocycline. The 
present observations show that minocycline and ceftriaxone promote survival of 
lesioned motoneurons in the mouse hypoglossal nucleus, and also suggest that 
alterations in glial responses might be involved in neuroprotective actions of 
antibiotics.