Chronic lesion development

For induction of stroke, occlusion of the middle cerebral artery (MCAO) for 60 min using the the intraluminal filament technique was used in male Wistar rats. Two basically different types of lesion were noted:

Type I consisted of exclusively subcortical damage, while type II, encompassed a cortico-subcortical lesion territory.

Following the lesion over 10 weeks, a primary hyperintensity on T2-weighted MR images was consistently observed during the first week, followed by a T2 normalization in both lesion types.
The (near-)normal T2 values persisted in the type I lesion during the following weeks. In the type II lesions, a later secondary increase in T2 was found. This means: two distinct T2 temporal profiles in the chronic phase could be discriminated.
Histological analysis led to the interpretation that persistent T2 normalization was characterized by selective neuronal death in the striatum. The secondary T2 increase of the type II lesion was characterized by pannecrosis followed by cystic transformation (and therefore T2 increase).
Thus, we have achieved the first MRI based differentiation between selective neuronal damage and pannecrosis, based on T2 temporal profile.

Combination with sensorimotoric behavior tests demonstrated that animals with type I lesions showed no behavior deficit. Animals with type II lesions, on the other hand, resulted in profound behavioral deficits.

Using histological analysis we could demonstrate that the fiber tracts through the striatum characterized by selective neuronal death and gliosis remained intact. This may account for the significantly better prognosis regarding functional deficits.
We are presently analyzing a longitudinal fMRI study (combined with SSEP recordings) to investigate the solidity of this morphological correlate for the animal’s functional status.

In collaboration with Per Wester from Umea, Sweden, we have established the photothrombotic ring model in the rat. This model produces a well defined ischemic core and a distinct peripheral region (penumbra) by virtue of this ring-wise illumination. Hereby, the penumbra is represented by the “donut hole” of the lesion. The core is formed by the ring-shaped torus of the illuminated tissue.

The lesion evolution has been characterized with multiple MRI parameters and histological, biochemical and autoradiographic imaging techniques. Thus, we could, on the one hand,  describe the acute time window of the first 6 hours following the lesion induction, and, on the other hand, the window of the chronic evolution phase during the following two weeks.