Long-Term Changes of Functional MRI–Based Brain Function, Behavioral Status, and Histopathology After Transient Focal Cerebral Ischemia in Rats

Abstract

Background and Purpose-The relation between recovery of brain function and neurological status after clinical and experimental cerebral ischemia is incompletely characterized. We assessed the evolution of ischemic injury, behavioral status, and brain activity at acute to chronic periods after transient middle cerebral artery occlusion (tMCAO) in rats. Methods-Male Sprague-Dawley rats were subjected to 20-minute tMCAO (nϭ10) or sham operation (nϭ10).Sensorimotor behavioral testing and multimodal (diffusion, perfusion, T2, and functional) MRI, as well as postmortem hematoxylin-eosin staining, were performed before and up to 21 days after tMCAO. MRI and histological parameters were evaluated in 5 regions of interest within the sensorimotor network. Diffusion, perfusion, and T2 lesion volumes were calculated according to previously established viability thresholds. Results-Diffusion and perfusion lesions were present during occlusion but disappeared completely and permanently within 30 minutes after reperfusion, with no T2 lesions seen. Functional MRI and behavioral deficits did not normalize until 1 and 21 days after tMCAO, respectively. Histology demonstrated selective neuronal cell death at 7 and 21 days after reperfusion. Conclusions-Twenty-minute tMCAO produced distinct changes on multimodal MRI, histology, and behavioral parameters acutely and chronically.

Incidence of New Diffusion-Weighted Imaging Lesions Outside the Area of Initial Hypoperfusion Within 1 Week After Acute Ischemic Stroke

“…Research in rats found that after 20 minutes middle cerebral artery occlusion, behavioral and histological anomalies remained although MRI parameters recovered. 14 In another study, histological examinations demonstrated neuronal necrosis both after transient and permanent recovery of DWI lesions after temporary middle cerebral artery occlusion; only the number of necrotic neurons differed between groups. 15 Although one should be cautious when interpreting animal studies with regard to patient analyses, these results further support the hypothesis that DWI lesions are not only associated with higher risk of future strokes, 1,2 cognitive decline, and depression, 3,4 but are also associated with permanent neuronal necrosis.…”

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).…”

“…These apparent discrepancies might reflect species differences but also the small degree of neuronal death in S1, the lack of co-registration between fMRI and histopathology, and the fact that fMRI was performed under general anesthesia, in the Sicard study. 42 Behavioral Correlates Although avoiding infarction of the penumbra markedly benefits behavioral outcome, 86,87 whether SNL may limit or delay functional recovery and plastic processes in the immediate periinfarct tissue, known to partly underlie recovery after cortical stroke, 86,88,89 is an important issue. In rats subjected to 20-minute proximal tMCAo inducing striatal SNL together with mild and inconsistent cortical SNL, Sicard et al 42 reported initial impairment but eventual full recovery in 3 weeks of subtle motor functions assessed by the adhesive test, which has been suggested to be specific to cortical lesions.…”

Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion

“…Although the histopathological changes were mild, more conspicuous behavioral effects might have been expected based on the single previous report on brief proximal MCAo in Sprague-Dawley rats. 44 However, the site of SNL is known to dictate the behavioral effects of stroke, with striatal SNL seemingly having less clear sensorimotor effects than cortical SNL. 16,45 Severe striatal SNL has, however, been reported to impair performance on sophisticated cognitive tests, 46,47 but these were not implemented in the present study.…”