White matter hyperintensities and post-stroke depression: A systematic review and meta-analysis.

INTRODUCTION: Post-stroke depression (PSD) is the most common emotional problem following a stroke. White matter hyperintensities (WMHs) are often reported in patients with a stroke, and are often divided into deep WMHs (DWMHs) and periventricular WMHs (PVWMHs). The relationship between WMHs and PSD remains controversial. This review aims to resolve this controversy. METHODS: A systematic search of electronic databases was conducted for studies. We extracted the relevant data and evaluated the study quality by using the Newcastle-Ottawa Scale. We pooled odds ratios (OR) for the same type of WMHs that were present in the relevant PSD period. RESULTS: 15 studies (n = 4133 patients) met our inclusion criteria. In the acute phase, WMHs, DWMHs, severe WMHs, and severe DWMHs were not significant risk factors for incident depression, but PVWMHs (pooled OR, 1.21; 95 % CI, 1.01-1.44) and severe PVWMHs (pooled OR, 1.72; 95 % CI, 1.12-2.65) had a significant association with PSD. In the subacute phase, DWMHs, DWMHs, and severe WMHs were not significantly associated with PSD, but PVWMHs (pooled OR, 2.44; 95 % CI, 1.25-4.76) showed a significant association with PSD. In the chronic phase, severe PVWMHs had no significant association with PSD, while WMHs (pooled OR, 1.063; 95 % CI, 1.03-1.09), DWMHs (pooled OR, 1.40; 95 % CI, 1.11-1.76), PVWMHs (pooled OR, 1.28; 95 % CI, 1.11-1.48), and severe DWMHs (pooled OR, 1.52; 95 % CI, 1.12-2.05) showed a significant association with PSD. CONCLUSION: We found a significant association between WMHs/DWMHs/PVWMHs and PSD in the chronic post-stroke phase. PVWMHs had a stronger correlation with PSD in each period after stroke than WMHs and DWMHs. High-quality prospective studies are still needed to fully resolve this relationship.

CDDO-Im exerts antidepressant-like effects via the Nrf2/ARE pathway in a rat model of post-stroke depression.

Increasing evidence suggests that oxidative damage and neuroinflammation play a critical role in the pathogenesis of post-stroke depression (PSD). These pathologic processes are tightly regulated by the NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. The synthetic triterpenoid, 2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im), is a potent Nrf2 activator. This study investigated whether CDDO-Im exhibited antidepressant-like activity and elucidated its protective mechanisms in a rat model of PSD, which was produced by middle cerebral artery occlusion (MCAO) followed by 28 days of chronic unpredictable mild stress (CUMS) in conjunction with solitary housing. The results demonstrated that CDDO-Im treatment markedly improved the depressive-like behaviors and reduced neuronal cell loss in the hippocampus, through decreasing the malondialdehyde (MDA) content (indicative of lipid peroxidation), superoxide dismutase (SOD), NF-kB activation, interleukin-6 (IL-6) and interleukin-1b (IL-1ß) in PSD rats. CDDO-Im treatment alleviated the oxidative stress and inflammatory response in PSD rats by promoting Nrf2 nuclear import and increasing the protein levels of Nrf2 downstream target genes, including heme oxygenase-1(HOMX1) and, quinone oxidoreductase-1(NQO1).These findings suggested that CDDO-Im treatment exhibited antidepressant-like effects and protected PSD rats from oxidative and inflammatory injury via the Nrf2/ARE pathway. Therefore, CDDO-Im treatment is worthy of further study.