We applied diffusion-weighted MRI (DWI) in the pilocarpine-induced status epilepticus (SE) model to investigate the evolution of acute phase changes in brain diffusion with and without early anticonvulsive therapy correlated to long-term SE-induced neuronal cell loss. Hereby, DWI was performed before (baseline) and serially between 3 and 120 min after onset of SE in untreated and treated animals (n=15 in each group). Anticonvulsive-treated animals received 20 mg/kg diazepam at 15 min after onset of SE. Apparent diffusion coefficients (ADC) were calculated for the parietal, temporal and piriform cortex, thalamus, hippocampus and amygdala and compared to baseline. Neuronal cell loss was quantified at 2 weeks after onset of SE utilizing cresyle-violet-staining. The results of ADC-mapping demonstrated a significant transient increase in ADC (to 116+/-4% of baseline) in the very acute phase starting 3 min after SE onset, lasting for 10 min in both groups. In untreated animals, there was a significant gradual decline in ADC to 75+/-12% of baseline while this decline in diazepam-treated animals was significantly less pronounced (P<0.05) and ADC recovered to 93+/-6% of baseline. There was good correlation between neuronal cell loss in specific brain regions at 2 weeks after SE and maximal decrease in ADC (r>0.79). In conclusion, serial DWI is a sensitive noninvasive technique for early detection, monitoring and prediction of SE-induced neuronal alterations. Using ADC-mapping, verification of early anticonvulsive therapy in SE seems to be possible as there is good correlation between the maximal decrease in ACD in the acute phase of SE and late neuronal cell loss.