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Altered functional connectivity in aged rat model

时间:2010-08-24 09:10:37  来源:  作者:

Subjects and Methods

The study was approved by the local ethical committee and was carried out in accordance with the guidelines for care and use of laboratory animals. A total of 18 Sprague-Dawley female aged rats (weighing 400–550g, approximately 22 months old) were subjected to neuroleptic anesthesia (40μg/kg fentanyl plus 500 μg/kg droperidol, intraperitoneal) for splenectomy. On preoperation and postoperative days 1,3,9, cognitive function was assessed in a Y maze, resting-state fMRI data were acquired using a 3.0T MR imaging system (ACHIEVA, Philips) with a 5 cm small animal surface coil. T2-weighted images were acquired by 3D turbo spin echo sequence (TR/TE: 2500/240 ms, slice thickness: 1 mm, matrix: 240x 240, flip angle: 90°).Functional images were acquired using single shot spin echo EPI sequence (TR/TE: 2000/27 ms, flip angle: 90 °, matrix: 64 × 41, FOV:41 cm, thickness/gap: 1/0mm, total 120 volumes, 20 axial slices). Data preprocessing included sclice timing, head-motion correction, spatial normalization, smoothing spatially with the FWHM by using SPM2 (http://www.fil.ion.ucl.ac.uk/spm/software/) .Further analyses were performed in MarsBar, including band-pass filtered (0.01 - 0.08Hz)(4) and selected the seed region of interest(ROI)(2×2 pixels). Two sample t-test was used to compare the functional connectivity maps difference between the group preoperation and group postoperation.

Results

Table1. Learning and spatial memory with Y maze

Group

Voltage of electric stimulation(V)

Learning(Time)

Pre-operation

35±8

29±7

1st after operation

71±7

69±24

3rd after operation

62±8

58±19

9th after operation

41±8

43±15

 

 

The time spent to learning and spatial memory in Y-maze test was significantly longer (p<0.01) in groups postoperative days 1,3 than in group preoperation.(Table1). Significant voxels (p < 0.001,) in the functional connectivity maps was reduced in right primary somatosensory cortex (SI) and in right hippocampus on the 1st, 3rd day after operation compared preoperation (Fig1)

 

left

SI

hp

Bregma+0.2mm

Fig. 1.Decreased functional connectional mapps in the right SI and hippocampus  (Bregma+0.2mm) in postoperation days 1,3 and 9.

 

Discussion & Conclusion

Our pilot study identified that surgery triggers a transient neurocognitive decline in a rat model. Surgical intervention significantly reduces functional connectivity maps with the primary somatosensory cortex and hippocampus, as compared with the pre-operation,which has not been previously reported. This has implications for how surgical intervention affects cortical and hippocampal activity, and for characterizing functional connectivity in rat brain networks. This pilot study also showed that fMRI is a reliable and accurate tool for clinical diagnosis of POCD in future.

Reference                                             

1. Newman S, et al. Anesthesiology. 2007 Mar;106(3):572-90.                         

2. Rombouts S, et al. Curr Alzheimer Res. 2005 Apr;2(2):115-6.

3. Wang L,et al. Neuroimage. 2006 Jun;31(2):496-504.                               

4. Fuqiang Zhao, et al.NeuroImage.2007,Epub.

5. Wan Y,et al. Anesthesiology. 2007 Mar;106(3):436-43.

  
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