'Not-so-minor' stroke: Lasting psychosocial consequences of anterior cingulate cortical ischemia in the rat.

Patients with small, non-debilitating strokes often report a reduction in quality of life due to persistent cognitive and emotional alterations. Stroke may directly damage limbic circuitry resulting in an impaired stress response, however the possibility that this may in part explain the prevalence of stroke comorbidity with mood disorders has yet to be determined. Here we systematically examine psychosocial consequences of prefrontal lesions targeting the left anterior cingulate cortex (ACC) using hormone assays and a behavioral test battery in adult rats to probe whether a small stroke could alter stress behavior or response to psychosocial stress (chronic mild stress (CMS) or subordination stress). Minor stroke produced chronic hyperactivity in an open field but did not alter fear-related inhibition in the elevated plus maze. Novelty-induced defecation was increased by the combination of CMS, subordination and stroke. Anterior cingulate lesions alone increased distress vocalizations in the water maze. Interestingly, ACC stroke caused hyper-secretion of porphyrin and long-term hormonal alterations that resulted in adrenal hypertrophy and enhanced dexamethasone suppression of the HPA axis. We propose that this behavioral profile is consistent with an animal model of post-stroke distress-like syndrome which could be useful in understanding how stroke affects the capacity to cope with psychological stress.

Impaired executive function following ischemic stroke in the rat medial prefrontal cortex.

Small (lacunar) infarcts frequently arise in frontal and midline thalamic regions in the absence of major stroke. Damage to these areas often leads to impairment of executive function likely as a result of interrupting connections of the prefrontal cortex. Thus, patients experience frontal-like symptoms such as impaired ability to shift ongoing behavior and attention. In contrast, executive dysfunction has not been demonstrated in rodent models of stroke, thereby limiting the development of potential therapies for human executive dysfunction. Male Sprague-Dawley rats (n=40) underwent either sham surgery or bilateral endothelin-1 injections in the mediodorsal nucleus of the thalamus or in the medial prefrontal cortex. Executive function was assessed using a rodent attention set shifting test that requires animals to shift attention to stimuli in different stimulus dimensions. Medial prefrontal cortex ischemia impaired attention shift performance between different stimulus dimensions while sparing stimulus discrimination and attention shifts within a stimulus dimension, indicating a selective attention set-shift deficit. Rats with mediodorsal thalamic lacunar damage did not exhibit a cognitive impairment relative to sham controls. The selective attention set shift impairment observed in this study is consistent with clinical data demonstrating selective executive disorders following stroke within specific sub-regions of frontal cortex. These data contribute to the development and validation of a preclinical animal model of executive dysfunction, that can be employed to identify potential therapies for ameliorating cognitive deficits following stroke.