7beta-Hydroxycholesterol has been previously demonstrated to inhibit
astrocytosis in injured cortex or spinal cord of rats. In this study, we explored the inhibitory effects of the
liposome containing
7beta-hydroxycholesterol on the reactive
astrocytosis caused by the injection of
iron into the hippocampus of rats and furthermore evaluated the involvement of reactive
astrocytosis in
iron-induced
epilepsy. Injection of
ferric chloride solution unilaterally into the hippocampus of rats induced spontaneous spiking activity ipsilaterally then developed into bilateral hippocampi and generalized convulsive
seizures within the first week post-operation, and spontaneous epileptiform activity and
generalized seizures lasted as long
as 2 weeks post-operation, whereas none of the rats injected with
sodium chloride solution unilaterally into the hippocampus developed
generalized seizures. With immunohistochemistry and Western blot analyses, apparent reactive
astrocytosis in bilateral hippocampi was detected using antibody against
glial fibrillary acidic protein 14 days after the injection of
ferric chloride solution, but no significant differences were found in the amount of
synaptophysin protein, a presynaptic vesicle
protein, as compared with the rats injected with
sodium chloride solution. Infusion of
liposome suspension containing
7beta-hydroxycholesterol into the same site immediately after the injection of
ferric chloride solution reduced the extent of the reactive
astrocytosis by 50%-55% of the amount of
glial fibrillary acidic protein in the hippocampi of both hemispheres, and non-significantly elevated the amount of
synaptophysin protein in both sides of hippocampus. However, these effects did not significantly modify the seizure latency and the incidence of
generalized seizures in the rats. These findings demonstrate the effects of
7beta-hydroxycholesterol on the inhibition of reactive
astrocytosis caused by
iron deposition in the hippocampus of rats, and suggest that the reactive
astrocytosis may not play a causal role in the development of
iron-induced
seizures.