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Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies
Published on: June 9, 2013
Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and
Victor E Yushmanov1, Alexander Kharlamov, Elena Simplaceanu
1Department of Anesthesiology, Allegheny-Singer Research Institute, Pittsburgh, PA 15212-4772, USA. vyushman@wpahs.org
Abstract:
The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the different character of edema between these models; yet, neither CBF nor ADCtr discriminated between them at 3.5 h, suggesting that different mechanisms of ischemic damage to the brain cells resulted in the same ADCtr value. CBF and ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/-10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT. CBF in homotopic normal cortex in the opposite hemisphere was higher for PT compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different pathological processes in the two models affect CBF, ADCtr and T1 in a unique, regionally specific manner. The PT model differs substantially from the MCAT and is not a model of cortical ischemia with an appreciable border zone.
Insights
Multiparametric MRI revealed distinct differences between middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT) models of cerebral ischemia. These models exhibit unique pathological processes affecting apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF), and T1 MRI parameters.
Area of Science:
- Neuroscience
- Radiology
- Pathology
Background:
- Cerebral ischemia research utilizes animal models to study stroke mechanisms.
- Understanding the differences between models like middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT) is crucial for accurate interpretation of experimental results.
- Multiparametric MRI offers a non-invasive approach to assess tissue damage and physiological changes in ischemic conditions.
Purpose of the Study:
- To compare and contrast the pathological and physiological characteristics of two distinct cerebral ischemia models: MCAT and PT.
- To investigate the utility of multiparametric MRI, including apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF), and T1-weighted imaging, in differentiating these models.
- To correlate MRI findings with histological markers of neuronal damage, such as Microtubule-associated protein-2 (MAP2) immunoreactivity.
Main Methods:
- Utilized multiparametric MRI (ADCtr, CBF, T1) to assess brain tissue in MCAT and PT models of cerebral ischemia.
- Employed Microtubule-associated protein-2 (MAP2) immunohistochemistry to map infarct extent and guide region-of-interest selection on MRI.
- Analyzed MRI parameters in the ischemic core, ischemic border zone, and homotopic contralateral cortex.
Main Results:
- The cortical photothrombosis (PT) model showed a significantly larger T1 increase in the ischemic cortex compared to the middle cerebral arterial transection (MCAT) model (42% vs. 16%), indicating different edema characteristics.
- Neither CBF nor ADCtr at 3.5 hours post-insult could differentiate between the MCAT and PT models, suggesting similar diffusion changes despite different injury mechanisms.
- The MCAT model exhibited reduced CBF and ADCtr in the ischemic border zone, indicative of marginal perfusion, which was not observed in the PT model.
- Cerebral blood flow in the homotopic normal cortex was higher in the PT model (199 ml/100 g/min) compared to the MCAT model (134 ml/100 g/min).
Conclusions:
- The PT model of cerebral ischemia differs significantly from the MCAT model, particularly in its lack of a distinct, hypoperfused border zone.
- Different pathological processes underlying MCAT and PT models impact CBF, ADCtr, and T1 values in a unique, regionally specific manner.
- The findings highlight the importance of model selection in cerebral ischemia research, as MRI parameters reflect distinct pathophysiological states.

