Glucocorticoid treatment in an ischaemic-like excitotoxic model of periventricular leucomalacia in mice.

OBJECTIVE

To determine the effects of fluorinated glucocorticoids on the occurrence and extent of ischaemic-like excitotoxic grey and white matter cerebral injuries in an animal model.

DESIGN

A study of the influence of single or repeated doses of glucocorticoids when creating excitotoxic lesions in mice pups, mimicking some aspects of periventricular leucomalacia and cortical-subcortical stroke as observed in human neonates.

SAMPLE: Four hundred and sixty-seven mouse pups out of more than 30 litters.

METHODS

An excitotoxic lesion was created by intracerebral injection of ibotenate, a glutamatergic agonist, in day five postnatal mice pups. A single dose of betamethasone or dexamethasone was administered, in a dose of 0.006-6 and 0.001-1 mg/kg, respectively, 24 hours before or 15 minutes after each ibotenate injection. Repeated doses of dexamethasone (0.01 mg/kg per day) or betamethasone (0.006 mg/kg) were given for five days before or after ibotenate injections. The measurement of white matter and grey matter lesions and the occurrence of cysts were assessed under light microscope on cresyl violet-stained brain sections.

MAIN OUTCOME MEASURES: Size of white matter cystic lesions.

RESULTS

A single injection of betamethasone or dexamethasone had a significant neuroprotective effect when administered after the excitotoxin. Betamethasone injected once prior to ibotenate also had a protective effect. Repeated administration of each steroid before or after excitotoxin injection provided more protection than a single injection.

CONCLUSION

Fluorinated glucocorticoids reduced neonatal brain lesions observed in a mouse model treated by excitotoxin injection.