AIMS: Disturbance of the balance between mitochondrial fission and fusion has 
been implicated in cerebral ischemia and several neurodegenerative diseases, 
whereas the underlying mechanisms remain poorly understood. In the present 
study, we attempted to investigate the role of dynamin-related protein 1 (Drp1), 
a key mitochondrial fission protein, in the pathogenesis of cerebral ischemia.
METHODS: Using Drp1 siRNA or Mdivi-1, a small molecule inhibitor of Drp1, we 
examined the effect of Drp1 knockdown or inhibition on oxygen-glucose 
deprivation (OGD)-induced mitochondrial dysfunction and death of SH-SY-5Y cells. 
Cell death and viability were evaluated with LDH and MTT assays, respectively, 
and mitochondrial morphology, mitochondrial membrane potential (Δψm), and ATP 
production were assessed using epifluorescence microscopy, flow cytometry, and 
HPLC, respectively. Moreover, to examine the effect of Drp1 inhibition on 
ischemic brain injury, middle cerebral artery occlusion (MCAO) mice were 
injected (i.p.) with Mdivi1, and blood-brain barrier permeability, brain water 
content, and cell apoptosis were assessed.
RESULTS: Knockdown or inhibition of Drp1 by Mdivi-1 significantly attenuated 
OGD-induced cell death in SH-SY-5Y cells, associated with reduced morphological 
change of mitochondria and attenuated Bax insertion,oligomerization. Moreover, 
treatment of the MCAO mice with Mdivi-1 remarkably reduced the infarct volume 
and neurological deficits in a dose-dependent manner, associated with marked 
reduction of mitochondrial fragmentation and BAX expression.
CONCLUSIONS: Down-regulation or inhibition of Drp1 may reduce cerebral ischemic 
damage through maintaining normal mitochondrial morphology and function, and 
decreasing Bax insertion and oligomerization in mitochondria.