Strain Differences in Fatigue and Depression after Experimental Stroke

Abstract

Fatigue and depression are common symptoms after stroke. Animal models of poststroke fatigue (PSF) and poststroke depression (PSD) would facilitate the study of these symptoms. Spontaneous locomotor activity is as an objective measure of fatigue and learned helplessness an accepted correlate of depression. We used different rat strains to evaluate stroke-induced changes in behavior in hopes that interstrain differences would provide insights into the biological basis of these symptoms. Male Lewis, Wistar, and Sprague-Dawley (SD) rats underwent experimental stroke. Spontaneous activity was assessed continually after stroke (for up to 50 days). In a subset of animals, the forced swim test was performed prior to and 1 month after stroke to assess learned helplessness; blood was obtained at sacrifice for cytokine assay. Stroke induced strain-related differences in activity; Lewis rats increased spontaneous activity during the dark cycle, while Wistar and SD rats increased activity during the light cycle. The velocity of movement decreased during the dark cycle in Wistar and SD rats and during the light cycle in Lewis rats. Stroke also led to an increase in learned helplessness in Lewis rats. In summary, different patterns of behaviors emerge in different rat strains after stroke. Lewis rats displayed behavior consistent with depression but not fatigue, while Wistar and SD rats displayed behavior consistent with fatigue but not depression. These data argue that PSF and PSD are different biological constructs and suggest that analysis of strain-related differences may provide insight into symptom pathophysiology.

Inflammation and the Silent Sequelae of Stroke

“…Following stroke, Lewis rats developed "learned helplessness", which is a proxy for depression [77]. SpragueDawley rats, however, evidenced "fatigue-like" behavior with a decrease in the velocity of movement; this strain did not develop behavior consistent with depression [77]. In this study, systemic levels of IL-1α correlated with "learned helplessness" and were higher in Lewis rats.…”

“…In this study, systemic levels of IL-1α correlated with "learned helplessness" and were higher in Lewis rats. Lower levels of IL1ra, however, were associated with a decrease in the velocity of movement and the distance moved [77]. These data show that differences in rat strains can be capitalized upon to study the origins of PSD and PSF, and that the inflammatory milieu in these strains likely affects the propensity to develop behaviors consistent with depression and fatigue.…”

“…Lewis rats are prone to inflammatory and autoimmune disorders, while Sprague-Dawley rats are more resistant to such diseases [76]. Following stroke, Lewis rats developed "learned helplessness", which is a proxy for depression [77]. SpragueDawley rats, however, evidenced "fatigue-like" behavior with a decrease in the velocity of movement; this strain did not develop behavior consistent with depression [77].…”

Mechanisms of poststroke fatigue

“…Animal models of stroke support this possibility. For instance, Kunze et al 85 showed that experimental stroke in Lewis rats resulted in behaviour consistent with depression, while Wistar and Sprague-Dawley rats exhibited sickness-like behaviour including fatigue-like behaviour. The role of genetic factors has also been taken into consideration in clinical studies.…”

Study on the behavioral changes of a post-stroke depression rat model

“…Mimicking the pathological and physiological processes of PSD in vivo, by simulating animal models of PSD, is important to enable the thorough elucidation of the occurrence, development and characteristics of PSD and to explore new therapeutic methods for the disease. Several studies have established an animal model of PSD (7,8), but only a few studies have focused on the behavioral changes in a PSD rat model (9). The aim of the present study, therefore, was to examine and evaluate these changes in a PSD rat model.…”