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Updated: Mar 22, 2026
Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies
Published on: June 9, 2013
Precise Characterization of the Penumbra Revealed by MRI: A Modified Photothrombotic Stroke Model Study
Cheng Qian1, Pei-Cheng Li1, Yun Jiao1
1Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
Aims:
To precisely characterize the penumbra by MRI based on a modified photothrombotic stroke mouse model.
Methods:
The proximal middle cerebral artery was occluded by a convenient laser system in conjunction with an intravenous injection of Rose Bengal in mice. And the suture MCAO model was performed in seven mice as a comparison of the reproducibility. One hour after occlusion, the penumbra was defined in six random photothrombotic stroke mice by mismatch between perfusion-weighted imaging and the apparent diffusion coefficient map on a home-made workstation. After imaging, three random mice of them were chosen to perform the reperfusion surgery. And the other three mice were sacrificed to stain for several potential penumbra markers, such as c-fos and heart shock protein 90. In the remaining mice, the evolution of the lesions was detected on the apparent diffusion coefficient map, diffusion-weighted imaging and T2-weighted imaging at 1, 3, 6, 12 and 24 hours. After evaluating the neurological deficit scores, the brains were sectioned and stained by triphenyltetrazolium chloride and Nissl.
Results:
The mice subjected to photothrombosis showed significant behavioral deficits. One hour after occlusion, the low perfusion areas on the perfusion-weighted imaging interlaced with the hypointense areas on the apparent diffusion coefficient map, demonstrating that the penumbra was located both surrounding and inside the lesions. This phenomenon was subsequently confirmed by the c-fos and heart shock protein 90 staining. The final T2-weighted images of the mice subjected to the reperfusion surgery were also consistent with the penumbra images at one hour. At early stages, the lesions were clearly identified on the apparent diffusion coefficient map; the volumes of the lesions on the diffusion-weighted imaging and T2-weighted imaging did not reach a maximum until 12 hours. The coefficient of variation (CV) of the final lesions in the photothrombotic stroke mice was 21.7% (0.08 of 0.37) on T2-weighted imaging and 27.8% (0.10 of 0.35) on triphenyltetrazolium chloride, representing a high reproducibility (n = 7). While the CV of the lesions in the MCAO stroke mice was only 70% (0.24 of 0.34, n = 4).
Conclusions:
This study has provided a precise imaging definition of the penumbra based on a reproducible photothrombotic stroke mouse model.
Insights
This study precisely defines the ischemic penumbra using MRI in a reproducible photothrombotic stroke mouse model. This imaging approach accurately characterizes the penumbra, aiding stroke research.
Area of Science:
- Neurology
- Medical Imaging
- Stroke Research
Background:
- The ischemic penumbra is a critical target for stroke treatment.
- Accurate characterization of the penumbra is essential for understanding stroke evolution and therapeutic efficacy.
Purpose of the Study:
- To precisely characterize the ischemic penumbra using MRI.
- To establish a reproducible photothrombotic stroke mouse model for penumbra imaging.
Main Methods:
- A modified photothrombotic stroke mouse model was created using laser occlusion and Rose Bengal injection.
- Magnetic Resonance Imaging (MRI), including perfusion-weighted imaging and apparent diffusion coefficient (ADC) maps, was used to define the penumbra.
- Lesion evolution, neurological deficits, and reproducibility were assessed and compared to the suture Middle Cerebral Artery Occlusion (MCAO) model.
Main Results:
- MRI revealed the penumbra surrounding and within lesions by identifying a mismatch between perfusion and ADC maps.
- Histological staining confirmed the presence of penumbra markers (c-fos, HSP90) in these regions.
- The photothrombotic model demonstrated high reproducibility (CV 21.7% on T2-weighted imaging) compared to the MCAO model (CV 70%).
Conclusions:
- A precise imaging definition of the ischemic penumbra was achieved.
- The modified photothrombotic stroke mouse model offers high reproducibility for penumbra characterization.
- This model facilitates accurate MRI-based assessment of the penumbra in stroke research.
