Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse.

Post-stroke patients describe suffering from persistent and unremitting levels of distress. Using an experimental model of focal cortical ischemia in adult male C57BL/6 mice, we examined whether exposure to chronic stress could modify the development of secondary thalamic neurodegeneration (STND), which is commonly reported to be associated with impaired functional recovery. We were particularly focused on the modulatory role of microglia-like cells, as several clinical studies have linked microglial activation to the development of STND. One month following the induction of cortical ischemia we identified that numbers of microglial-like cells, as well as putative markers of microglial structural reorganization (Iba-1), complement processing (CD11b), phagocytosis (CD68), and antigen presentation (MHC-II) were all significantly elevated in response to occlusion. We further identified that these changes co-occurred with a decrease in the numbers of mature neurons within the thalamus. Occluded animals that were also exposed to chronic stress exhibited significantly lower levels of Iba-1 positive cells and a reduced expression of Iba-1 and CD11b compared to the 'occlusion-alone' group. Interestingly, the dampened expression of microglial/monocyte markers observed in stressed animals was associated with significant additional loss of neurons. These findings indicate that the process of STND can be negatively modified, potentially in a microglial dependent manner, by exposure to chronic stress.

Photothrombotic stroke induces persistent ipsilateral and contralateral astrogliosis in key cognitive control nuclei.

While astrocytes are recognised to play a central role in repair processes following stroke, at this stage we do not have a clear understanding of how these cells are engaged during the chronic recovery phase. Accordingly, the principal aim of this study was to undertake a quantitative multi-regional investigation of astrocytes throughout the recovery process. Specifically, we have induced experimental vascular occlusion using cold-light photothrombotic occlusion of the somatosensory/motor cortex in adult male C57B6 mice. Four weeks following occlusion we collected, processed, and immunolabelled tissue using an antibody directed at the glial fibrillary acidic protein (GFAP), an astrocyte specific cytoskeletal protein marker. We investigated GFAP changes in 13 regions in both the contra- and ipsi-lateral hemispheres from control and occluded animals. Specifically, we examined the infra-limbic (A24a), pre-limbic (A25), anterior cingulate (A32), motor (M1 and M2) cortices, the forceps minor fibre tract, as well the shell of the accumbens, thalamus, cingulate cortex (A29c), hippocampus (CA1-3) and lateral hypothalamus. Tissue from occluded animals was compared against sham treated controls. We have identified that the focal occlusion produced significant astrogliosis (p < 0.05), as defined by a marked elevation in GFAP expression, within all 13 sites assessed within the ipsilateral (lesioned) hemisphere. We further observed significant increases in GFAP expression (p < 0.05) in 9 of the 13 contralesional sites examined. This work underscores that both the ipsilateral and contralesional hemispheres, at sites distal to the infarct, are very active many weeks after the initial occlusion, a finding that potentially has significant implications for understanding and improving the regeneration of the damaged brain.

Stress as necessary component of realistic recovery in animal models of experimental stroke.

Over the last decade there has been a considerable effort directed toward reformulating the standard approach taken to preclinically model stroke and stroke recovery. The principal objective of this undertaking has been to improve the success with which preclinical findings can be translated. Although several advancements have already been introduced, one potentially critical feature that appears to have been overlooked is psychological stress. Stroke is well recognized to produce high levels of stress in patients, and ongoing exposure to stress is recognized to deleteriously interfere with recovery. The presence of high levels of stress (distress) in stroke patients is also relevant because nearly all clinically deployed neurorestorative interventions occur against this background. Somewhat perplexingly, however, we could find no preclinical stroke studies concerned with investigating the efficacy of putative neurorestorative compounds that did so in the presence of stress. The following article will make the case that failure to recognize or compensate for the effects of ongoing stress in standard preclinical experimental models of recovery is likely to result in overestimation of the effectiveness of pharmacological or behavioral neurorestorative interventions.

Tracking changing environments: innovators are fast, but not flexible learners.

Behavioural innovations are increasingly thought to provide a rich source of phenotypic plasticity and evolutionary change. Innovation propensity shows substantial variation across avian taxa and provides an adaptive mechanism by which behaviour is flexibly adjusted to changing environmental conditions. Here, we tested for the first time the prediction that inter-individual variation in innovation propensity is equally a measure of behavioural flexibility. We used Indian mynas, Sturnus tristis, a highly successful worldwide invader. Results revealed that mynas that solved an extractive foraging task more quickly learnt to discriminate between a cue that predicted food, and one that did not more quickly. However, fast innovators were slower to change their behaviour when the significance of the food cues changed. This unexpected finding appears at odds with the well-established view that avian taxa with larger brains relative to their body size, and therefore greater neural processing power, are both faster, and more flexible learners. We speculate that the existence of this relationship across taxa can be reconciled with its absence within species by assuming that fast, innovative learners and non innovative, slow, flexible learners constitute two separate individual strategies, which are both underpinned by enhanced neural processing power. This idea is consistent with the recent proposal that individuals may differ consistently in 'cognitive style', differentially trading off speed against accuracy in cognitive tasks.