Temporal profile of T₂-Weighted MRI Distinguishes between Pannecrosis and Selective Neuronal Death after Transient Focal Cerebral Ischemia in the Rat

Abstract

Transient middle cerebral artery occlusion (MCAO) by an intraluminal thread leads to primarily subcortical infarctions with little sensorimotor impairment in the Wistar rat strain. We investigated the course of infarct development in this lesion type for 10 weeks using magnetic resonance imaging (MRI) along with histological characterization. MCAO was induced in male Wistar rats (260 to 300 g) for 60 mins. Animals received follow-up T 1 -and T 2 -weighted MRI from day 1 until week 10. Separate groups of animals were analyzed histologically after 2, 6, and 10 weeks. Histology included immunohistochemistry for neuronal and astrocytic markers as well as hematoxylin eosin and luxol fast blue-cresyl violet staining. In contrast to lesions involving the cortex, exclusively subcortical infarctions were characterized by a complete resolution of initially increased T 1 and T 2 relaxation times by 10 weeks. Between 2 and 10 weeks, neuronal death and gliosis as well as a dense inflammatory infiltrate were evident in these lesions, without damage to fiber tracts or development of cystic cavities. Exclusively subcortical lesions in Wistar rats are characterized by normalization of T 1 and T 2 relaxation times, which might, however, not be mistaken for tissue recovery. Despite this MRI normalization, selective neuronal death and gliosis develop. Although MRI at individual time points might therefore be ambiguous, the temporal profile of relaxation time changes over the chronic time period allows discrimination of the lesion development into selective neuronal death or pannecrosis.

Selective Neuronal Loss in Ischemic Stroke and Cerebrovascular Disease

“…These slowly evolving striatal changes were associated with increasingly impaired behavioral tests, and biochemical analyses showed high tissue amounts of manganese. This pattern of MR changes, which strikingly differs from known poststroke changes but is reminiscent of findings in anoxic or hypoglycemic coma (see above), has been replicated once regarding T1, 82 while transient day 1 striatal T2-hyperintense lesion, but no T1 changes, was observed in some rats in Wegener et al 39 60-minute proximal MCAo study , associated with very severe SNL and inflammation as in Fujioka's study. This MR pattern may reflect accumulation in tissues of agents that shorten T1 and T2 relaxation times, such as iron and manganese 59,82 or reactive oxygen species.…”

“…The latter is preferred because with the former cortical ischemia is not only less severe but also less consistent. 39,48 Using proximal MCAo in rats, scattered patches of cortical SNL but virtually no infarction is observed following p30 minutes of proximal MCAo, 10,11,[35][36][37]40,42,49 the only exception being Zhan et al, 38 but see caveats above. However, cortical SNL was found not to affect every subject, being for instance observed in 40% of rats subjected to 10-to 25-minute tMCAo.…”

The Effects of Delayed Reduction of Tonic Inhibition on Ischemic Lesion and Sensorimotor Function

“…below the mean signal in the corresponding contralesional region of interest were classified as necrotic tissue. [20][21][22][23] Single voxel dilation and small hole (o 6 voxels in three-dimensional diameter) filling were applied within slices and between Figure 2).…”

Delayed changes in T1‐weighted signal intensity in a rat model of 15‐minute transient focal ischemia studied by magnetic resonance imaging/spectroscopy and synchrotron radiation X‐ray fluorescence

“…For instance, transient focal ischemia with a duration of 15 min results exclusively in subcortical (CP) lesions, which show normal T 1 and elevated T 2 at 3 days, but have elevated T 1 -weighted (T 1 W) signal intensity (SI) and reduced T 2 -weighted (T 2 W) SI at 2 weeks after ischemia, likely due to simultaneous decreases in both T 1 and T 2 in the ischemic lesion (4,5). On the other hand, transient focal ischemia with a duration of 60 min induces brain lesions of two distinct types (CP lesions and cortico-subcortical (CP ϩ ) lesions), which develop and mature with different time courses reflecting different mechanisms of neurodegeneration (6,7). At 2 weeks after ischemia, CP lesions resulting from 60-min focal ischemia are characterized by normal T 1 and T 2 , while the CP ϩ lesions are frequently associated with elevated T 1 and T 2 (6).…”

“…On the other hand, transient focal ischemia with a duration of 60 min induces brain lesions of two distinct types (CP lesions and cortico-subcortical (CP ϩ ) lesions), which develop and mature with different time courses reflecting different mechanisms of neurodegeneration (6,7). At 2 weeks after ischemia, CP lesions resulting from 60-min focal ischemia are characterized by normal T 1 and T 2 , while the CP ϩ lesions are frequently associated with elevated T 1 and T 2 (6).…”