Objective To explore the feasibility of PPAR-γ1 gene transfection via intracerebroventricular injection and possible protective effect against cerebral ischemia reperfusion injury.Methods Ninety adult male SD rats were randomly divided into 6 groups(n=18).In group Ⅰ,the rats were intracerebroventricularly injected with normal saline 0.1 ml.In group Ⅱ,the rats were injected with empty adenoviral(Adv)vector 0.1 ml.In group Ⅲ,the rats were injected with 0.1 ml Adv-PPAR-γ1 and the group Ⅳ received Adv-EGFP 0.1 ml.The group Ⅴ was intragastrically administered with Pioglitazone.After 3 days,middle cerebral artery occlusion model was established.The group I was sham-operation group.In group Ⅱ-Ⅴ middle cerebral artery was obstructed for 90 min followed by reperfusion for 24 h.Twenty-four hours after operation,samples were collected.The expression of green fluorescent protein in Group Ⅳ was observed with fluorescence microscope to assess the adenovirus-mediated transfection.The cerebral infarction volume was measured by triphenyltetrazolium chloride(TTC)staining.The permeability of blood-brain barrier was determined by Evan's blue.Brain water was calculated by wet-dry weight method.The histopathology was observed under light microscope and electron microscope.The activity of myeloperoxidase(MPO)was tested.The expressions of IL-1β,inter-cellular adhesion mdecule-1(ICAM-1),aquaporin protein(AQP-4)and matrix metalloproteinase-9(MMP-9)protein were determined by Western Blotting.Results After the animals were intracerebroventricularly administered Adv-EGFP plasmid,that the fluorescence for EGFP was positive in brain tissue suggested the successful transfection of viral gene.In response to I/R injury,the permeability of blood-brain barrier(0.094 5±0.009 5),brain water(87.4±4.7),and the activity of MPO were dramatically increased(0.213±0.044)as well as the cerebral infarction volume(42.3±2.6).The expressions of IL-1β(0.84±0.05),ICAM-1(0.85±0.07),AQP-4(0.84±0.06)and MMP-9(0.80±0.03)protein were up-regulated.Either intracerebroventricularly injection with Adv-PPAR-γ1 or intragastric administration with Pioglitazone could reduce the cerebral infarction volume(35.7±2.5,32.2±5.9),the permeability of blood-brain barrier(0.077 4±0.008 8,0.073 7±0.006 4),brain water(82.9±4.7,84.5±5.5),the activity of MPO(0.151±0.018,0.166±0.026)and the expression of IL-1β(0.71±0.04,0.75±0.05),ICAM-1(0.69±0.03,0.79±0.07),AQP-4(0.77±0.04,0.78±0.06)and MMP-9 (0.76±0.06,0.77±0.05)protein.Conclusions Transfection of via cerebral ventricle It was feasible to transfect the PPAR-γ1 gene into brain tissue via intracerebroventricular injection of the adenoviral vector and demonstrated the protective effect against cerebral ischemia reperfusion injury. Key words: PPAR-γ1; Cerebral ischemia/reperfusion injury; Gene transfection