Transient and Permanent Resolution of Ischemic Lesions on Diffusion-Weighted Imaging After Brief Periods of Focal Ischemia in Rats

Abstract

Background and Purpose-The early ischemic lesions demonstrated by diffusion-weighted imaging (DWI) are potentially reversible. The purposes of this study were to determine whether resolution of initial DWI lesions is transient or permanent after different brief periods of focal brain ischemia and to evaluate histological outcomes. Methods-Sixteen rats were subjected to 10 minutes (nϭ7) or 30 minutes (nϭ7) of temporary middle cerebral artery occlusion or sham operation (nϭ2). DWI, perfusion-weighted imaging (PWI), and T 2 -weighted imaging (T 2 WI) were performed during occlusion; immediately after reperfusion; and at 0.5, 1.0, 1.5, 12, 24, 48, and 72 hours after reperfusion. After the last MRI study, the brains were fixed, sectioned, stained with hematoxylin and eosin, and evaluated for neuronal necrosis. Results-No MRI or histological abnormalities were observed in the sham-operated rats. In both the 10-minute and 30-minute groups, the perfusion deficits and DWI hyperintensities that occurred during occlusion disappeared shortly after reperfusion. The DWI, PWI, and T 2 WI results remained normal thereafter in the 10-minute group, whereas secondary DWI hyperintensity and T 2 WI abnormalities developed at the 12-hour observation point in the 30-minute group. Histological examinations demonstrated neuronal necrosis in both groups, but the number of necrotic neurons was significantly higher in the 30-minute group (95Ϯ4%) than in the 10-minute group (17Ϯ10%, PϽ0.0001). Conclusions-Transient

Selective Neuronal Loss in Ischemic Stroke and Cerebrovascular Disease

“…Experimentally, areas that develop histopathological SNL X48 hours after tMCAo regularly display apparent diffusion coefficient/diffusion-weighted imaging (DWI) lesions acutely, indicating severe ischemia. 37,40,42 Diffusionweighted imaging lesions affected by SNL completely vanish after reperfusion 37,42 and do not reappear secondarily 42 (Figure 4). Conversely, DWI lesions that reappear secondarily are generally T2-hyperintense and exhibit pannecrosis histopathologically, 40,41 although very severe SNL in the caudoputamen has been reported in some rats with this imaging pattern 40 (Figure 4).…”

“…Histopathology showed moderate selective neuronal death (4% to 28% necrotic neurons) in the caudoputamen with no instance of infarction in the 10-minute group, and massive neuronal death or pannecrosis in all 30-minute group subjects (88% to 100% necrotic neurons). From Li et al, 40 with permission. eventual outcome in man.…”

Normobaric Hyperoxia Delays Perfusion/Diffusion Mismatch Evolution, Reduces Infarct Volume, and Differentially Affects Neuronal Cell Death Pathways after Suture Middle Cerebral Artery Occlusion in Rats

“…Lastly, since the ISEL procedure stains predominantly apoptotic (and to a lesser degree necrotic) cells (Wijsman et al, 1993), H&E staining was used to exemplarily confirm cell death. Briefly, neurons were classified as necrotic when they exhibited pyknosis, karyorrhexis, karyolysis, cytoplasmic eosinophilia ('red neuron'), or loss of affinity for hematoxylin ('ghost neuron') (Li et al, 2000). Apoptotic neurons were identified by the criteria of Li et al (1998b), that is, via the presence of membrane-bound apoptotic bodies of roughly round or ovoid shape.…”

Spectacular Shrinking Deficit: Insights from Multimodal Magnetic Resonance Imaging after Embolic Middle Cerebral Artery Occlusion in Sprague—Dawley Rats

“…Additionally, depending on the duration of the occlusion, secondary abnormalities may develop on diffusion-weighted imaging (DWI) and T 2 -weighted imaging (T2WI) (Li et al, 2000;Neumann-Haefelin et al, 2000). These findings are intriguing as both transient and permanent resolution of such abnormalities was observed in SSD patients (Baird et al, 1995;Fujioka et al, 1999a;Kraemer et al, 2005).…”

“…As it has been shown that severe dysfunctions in cerebral activity and neurobehavior can persist despite normal appearing brain on DWI, perfusion-weighted imaging (PWI), and T2WI , further research is warranted to understand the mechanisms underlying SSD. However, most experimental data regarding transient MCAO were derived with suture MCAO models (Li et al, 2000;Neumann-Haefelin et al, 2000;Sicard et al, 2006), which do not reliably reproduce the inhomogeneous vascular findings in patients suffering from acute territorial stroke (Adams et al, 2005).…”