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Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation
Authors:YC Huang  WS Tzeng  CC Wang  BC Cheng  YK Chang  HH Chen  PC Lin  TY Huang  TJ Chuang  JW Lin  CP Chang
Institution:1. Department of Radiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan;2. Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan;3. Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan;4. Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;5. Department of Radiological Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan;6. Department of Information Technology, College of Health and Information, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;g Department of Child Care, Southern Taiwan University of Science and Technology, Tainan, Taiwan;h Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;i Department of Neurosurgery, Taipei Medical University-Shuang-Ho Hospital; and Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan
Abstract:

Purpose

This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation.

Materials and methods

Following surgical induction of MCAO for 90 min, agmatine was injected 5 min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3 h–72 h in a 1.5 T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections.

Results

Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3 h and peaked at 24 h–48 h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72 h) point except for significantly smaller ADC lesions in the MCAO model (P < 0.05). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived on T2WI, DWI or CE-T1WI than ADC (P < 0.05). At the last imaging time point, a significant increase in Evans Blue extravasation and a significant decrease in Nissl-positive cells numbers were noted in the vehicle-treated MCAO injured animals. The lesion volumes derived from T2WI, DWI, CE-T1WI, and Evans blue extravasation as well as the reduced numbers of Nissl-positive cells were all significantly attenuated in the agmatine-treated rats compared with the control ischemia rats (P < 0.05).

Conclusion

Our results suggest that agmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia.
Keywords:MCAO  middle cerebral artery occlusion  MRI  magnetic resonance imaging  T2WI  T2-weighted images  DWI  diffusion-weighted images  ADC  apparent diffusion coefficient  CE-T1WI  contrast-enhanced T1-weighted images  TTC  triphenyltetrazolium chloride  BBB  blood&ndash  brain-barrier  PBS  phosphate-buffered saline  ROI  region of interest  ANOVA  analysis of variance  EB  Evans blue  AQP4  aquaporin 4
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