Objective      To observe the effects of MK801 and SB203580 on N-methyl-D-aspartic acid (NMDA)-induced cerebral cortical neuron injury and to determine the role and possible action mechanism of p38 mitogen-activated protein kinases (p38MAPK) signaling pathway in neuron injury.       Methods      Newborn SD rat cortical neurons were cultured for 7 d

and then randomly assigned to 5 groups: a control group

an NMDA injury group

an MK801 interventional group

a

n SB203580 interventional group

and a combined interventional group (SB203580+MK801). MTT assay and lactate dehydrogenase (LDH) release assay were employed to assess primary neuron viability and cell membrane damage

respectively. Acridine orange/ethidium bromide (AO/EB) double fluorescent staining was used to observe morphology and cell apoptosis. Expression of p-p38MAPK

Bcl-2 and BAX was observed separately by IHC and Western blotting.       Results      Compared to the control group

markedly decreased cell viability

significantly increased LDH leakage and apoptotic cell number

increased expression of p-p38MAPK and BAX

and decreased expression of Bcl-2 were observed in the NMDA injury group (

P

0.05

P

0.01). Compared to the NMDA injury group

MK801 and/or SB203580 improved cell viability

reduced LDH release rate and apoptosis

decreased the expression of p-p38MAPK and BAX

and increased the expression of Bcl-2 (

P

0.05

P

0.01) in the interventional groups.       Conclusion      MK801 and SB203580 have protective effects on neurons with NMDA-induced injury. MK801 may protect the neurons from NMDA-induced injury through p38MAPK signaling pathway. The common mechanism involves partial inhibition of p38MAPK signaling pathway-mediated apoptosis-related proteins.