Objective   To investigate the effect of conventional treatment

especially with multidrug

for neonatal seizure on rat brain development.  Methods   A total of 120 7-day-old rats were divided into 6 treatment groups (n=20). Each group was treated with following conventional seizure drugs at a dose determined according to clinical neonatal baby doses

Phenobarbital (PB)

Diazepam (DZP)

Phenytoin (PHT)

Phenobarbital in combination with Diazepam (PB+DZP)

Phenobarbital in combination with Phenytoin (PB+PHT) or normal saline respectively by intraperitoneal injection(i.p). In 24 h later

plasma neuron-specific enolase (NSE) was determined by ELISA. Expression levels of apoptosisrelated proteins Bax and Bcl-2 in the brain neurocytes was detected by immunohistochemistry. Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL). The effects of anticonvulsant drugs on cognitive function were assessed by Morris water maze. Histological changes of brain were observed by HE and Nissl staining.  Results  The concentration of plasma NSE exposed to PB

PHT

PB+DZP and PB+PHT was significantly increased by 52.48%

67.02%

152.48% and 175.53% respectively compared with controls [(0.282±0.1340) ng/L] (P0.01)

and the NSE exposed to PB+DZP and PB+PHT significantly was increased by 65.58% and 80.20% respectively compared with PB group (P0.01). The expression of Bax protein was significantly elevated in all treatment groups compared with controls (P0.05). But the expression Bcl-2 protein was significantly decreased in the PB+PHT group compared to control (P0.05). While the number of TUNEL positive cells in the subicular complex exposed to PB

DZP and PHT was significantly increased by 4.74-fold

3.27-fold and 5.44-fold respectively compared with control group (P0.01)

moreover

exposure to PB+DZP and PB+PHT were significantly increased by 1.31-fold and 1.47-fold compared with PB group (P0.01). The rats treated with PB+DZP and PB+PHT always performed worse than controls in Morris water maze. Significant decrease in the number of neurons were observed in subicular complex of rats at postnatal day 30 exposed to PHT

PB+DZP and PB+PHT compared with controls.  Conclusion  PB

DZP and PHT treatment for neonatal seizure can cause acute brain damage. The brain damage will get partly recovered in 3 weeks later

and will not cause cognitive impairment. However

PB+DZP and PB+PHT administration result in more sever brain damage

and even persistent cognitive impairment in neonatal rats.