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.