Synaptic density of axotomized hypoglossal motorneurons following pharmacological blockade of the microglial cell proliferation.

The purpose of the present study was to examine the possible role of reactive microglia in the removal of presynaptic terminals following motor axon injury. Quantitative electron microscopy was used to examine synaptic numbers and total relative synaptic coverage on hypoglossal neuronal perikarya following hypoglossal nerve transection in the rat with or without pharmacological blockade of the axotomy-induced microglial cell proliferation. In a previous study we have shown that the axotomy-induced microglial cell proliferation is selectively inhibited by continuous infusion of cytosine-arabinoside (ARA-C) into the ventricular system of the adult rat brain. Adopting this procedure in the present study resulted in an almost complete elimination of reactive microglia. There was a statistically significant decrease in the number of synapses and the relative synaptic coverage in untreated as well as ARA-C-treated animals 4 and 7 days after nerve transection. Immunocytochemical labeling of terminals in the hypoglossal nucleus using antibodies to synaptophysin showed a reduction in immunoreactivity around hypoglossal nerve cell bodies ipsilateral to nerve transection in both groups of animals. These results indicate that reactive microglia are not responsible for detachment of presynaptic terminals following motor axon injury.