Table 2.
Effects of psychological stress and glucocorticoids in experimental stroke models
| Stress and ischaemia model | Results | |
|---|---|---|
| Studies in mice | ||
| Balkaya et al., 2011 | Chronic stress paradigm over 28 days; treatment with glucocorticoid receptor antagonist mifepristone or vehicle; subsequently, mice are subjected to 30 min MCAo/reperfusion; assessment of histological stroke damage at 72 h after MCAo | Stress causes increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Stress confers major increases in ischaemic lesion size. The negative effects of stress are reversed by mifepristone. |
| Caso et al., 2008 | Immobilization (1 h for 7 days) prior to permanent MCAO by electrocoagulation; assessment of histological stroke damage at 24 h after MCAO | Immobilization stress increases infarct size, lipid peroxidation and iNOS expression; these effects of stress on stroke outcome are attenuated in TLR4-deficient mice |
| Custodis et al., 2011 | Chronic stress paradigm over 28 days; treatment with I(f)-channel inhibitor ivabradine (10 mg·kg−1 per day) or vehicle; subsequently, mice are subjected to 30 min MCAo/reperfusion; assessment of histological stroke damage at 72 h after MCAo | Stress impairs endothelial function, exacerbates vascular and brain oxidative stress, and increases infarct size. Heart rate reduction with ivabradine restores endothelial function, reduces oxidative stress, and reduces lesion size. |
| DeVries et al., 2001,2001 | Social stress paradigm over 3 days; last stress session approximately 1 h before induction of cerebral ischaemia by 60 min MCAo/reperfusion; assessment of histological stroke damage at 24 h after MCAo | Stress increases infarct size and reduces bcl-2 mRNA levels in the ischaemic hemisphere; significant inverse correlation between post-stroke corticosterone levels and bcl-2 mRNA levels |
| Karelina et al., 2009 | Social isolation or social housing for 2 weeks before surgery and throughout reperfusion period; 60 min MCAo/reperfusion. | Peri-ischaemic social isolation decreases post-stroke survival and exacerbates infarct size and oedema development; central IL-6 signalling is down-regulated and peripheral IL-6 is up-regulated in isolated mice. |
| O’Keefe et al., 2014 | 60 min of reversible right MCAo; investigation of the subacute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome; open field test, elevated zero maze, Porsolt’s forced swim test | No effect of stroke on locomotor activity; no difference in anxiety-like behaviour between groups; however, worsened histological damage from ischaemic injury and an increase in depressive-like behaviour in isolated mice as compared with pair-housed mice. Mice isolated immediately after stroke show a decrease in the serum levels of BDNF. |
| Sorrells et al., 2013 | Implantation of s.c. corticosterone pellets; MCA permanently occluded by electrocoagulation; assessment of histological stroke damage at 24 h after MCAO | Pre-MCAO glucocorticoids worsen MCAO damage in wild-type mice; key role of glucocorticoid signalling in myeloid and endothelial cells in mediating this effect |
| Sugo et al., 2002 | Social stress (45 min) or injection with 1 mg·kg−1 corticosterone or vehicle for 7 days; mice subjected to social stress were injected with 1 mg·kg−1 mifepristone (glucocorticoid receptor antagonist) or vehicle; stroke induced by 60 min of intraluminal MCAo | Chronic social stress or exogenous corticosterone before MCAo result in larger infarcts at 72 h. Effect of social stress on infarct volume is reversed by pretreatment with mifepristone. |
| Venna et al., 2012 | Social isolation or social housing for 7 days before surgery and throughout reperfusion period; 90 min MCAo/reperfusion | Peri-ischaemic social isolation increases infarct size (72 h) and expression of NF-κB |
| Caso et al., 2006 | immobilization (1 h for 7 days) prior to permanent MCAO; assessment of infarct volume at 24 h after MCAO | Immobilization stress increases infarct size; this relates to increased iNOS expression and lipid peroxidation, and increased TNF-α levels |
| Madrigal et al., 2003 | Subacute (1 h for 7 days) or chronic (6 h for 21 days) immobilization stress 24 h before permanent MCAO; assessment of infarct volume at 48 h after MCAO | Subacute immobilization stress increases brain infarct volume; chronic immobilization stress reduces brain infarct volume |