Preischemic hyperglycemia exacerbates brain damage caused by cerebral ischemia. 
In the present experiment, we studied the effects of preischemic hyperglycemia 
on protein markers that are related to mitochondrial fission and fusion, 
mitochondrial biogenesis, and autophagy in mice subjected to 30-min transient 
focal ischemia. The fission proteins dynamin-related protein 1 (Drp1) and 
fission 1 (Fis1), fusion proteins optic atrophy 1 (Opa1) and mitofusin 2 (Mfn2), 
mitochondrial biogenesis regulators nuclear respiratory factor 1 (NRF1) and 
peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), 
and autophagy marker beclin 1 and microtubule-associated protein light chain 3 
(LC3) were analyzed in control, 30 min middle cerebral artery occlusion (MCAO) 
plus 6-, 24-, and 72 h of reperfusion in normo- and hyperglycemic conditions. 
Cerebral ischemia increased the levels of Drp1 and decreased Fis1 after 
reperfusion. Preischemic hyperglycemia further augmented the increase of Drp1 
and induced elevation in Fis1. Ischemia inhibited the levels of Opa1 and Mfn2 
and hyperglycemia further decreased the level of Opa1. Further, NRF1 increased 
after reperfusion in both normo- and hyperglycemic animals. However, such 
increase was caused by reperfusion rather than glucose level. Finally, ischemia 
increased beclin 1 level at 6 and 24 h of reperfusion and hyperglycemia further 
increased the beclin 1 level and caused LC3-II increase as well. Hyperglycemia 
enhances the ischemia-induced mitochondrial dynamic imbalance towards fission 
that may favor mitochondrial fragmentation and subsequent damage. Hyperglycemia 
elevated autophagy markers may represent an adapting reaction to the severe 
damage incurred in hyperglycemic animals or a third pathway of cell death.