Table 1.
Dual in vivo effects of HO-1 and its metabolites in various neurovascular diseases.
| HO-1 and Its Metabolites (Function) | Summary (In Vivo) | Species | Disease | Ref. |
|---|---|---|---|---|
| HO-1 (beneficial) | HO- siRNA-treated retina demonstrates macrophage infiltration and severe destruction of the retinal structure. | Rat | IR injury | [112] |
| HO-1 (beneficial) | Gene transfer of HO-1 in IR activates BDNF-TrkB signaling pathway. | Rat | IR injury | [118] |
| HO-1 (detrimental) | Sustained HO-1 overexpression in transgenic mice facilitates tau aggregation in brains. | Mouse | AD | [134] |
| CO (beneficial) | CORM (ALF-186) is intravitreally applied into the left eyes of rats directly after retinal IR injury, resulting in enhanced retinal ganglion cells, reduction of inflammatory and apoptotic gene expression. | Rat | IR injury | [115] |
| CO (beneficial) | 250 ppm CO is applied to MCAO mouse model, resulting in translocation of Nrf2 to nucleus, elevates HO-1 expression and reduced infarct size. | Mouse | IR injury | [51] |
| CO (beneficial) | CORM-3 reduces BBB leakage, pericyte cell death and oxidative stress-mediated HIF-1α expression and induces neurogenesis through activation of the NOS/HO pathway. | Mouse | TBI | [23] |
| CO (beneficial) | 250 ppm CO treatment can prevent the pericyte cell death and promote neurogenesis. | Mouse | TBI | [23] |
| Bilirubin (beneficial) | Plasma bilirubin levels were increased on days 2, 3 and 4 in TBI patients, leading to an increase in antioxidant activity. | Human | TBI | [127] |
| Bilirubin (beneficial) | Soluble bilirubin nanoparticles protect mice from IR injury through attenuation of oxidative stress, apoptosis, and inflammation. | Mouse | IR injury | [113] |
| Bilirubin (detrimental) | Gilbert’s syndrome subjects demonstrate higher concentration of unconjugated bilirubin, carboxy hemoglobin and iron compared with control subjects. | Human | Gilbert’s syndrome | [132] |
| Iron (detrimental) | Increased cardioembolic stroke risk is related to increased serum iron and lower transferrin levels. | Human | IR injury | [110] |
| [96,97] Iron (detrimental) | More iron and transferrin in retinal pigment epithelium in AMD patients than age-mated controls. | Human | AMD | [98,99] |
| Iron (detrimental) | Iron deposition is increased during 3, 7, 14, 28 days in ipsilateral core-region. | Mouse | TBI | [121,122] |
| Iron (detrimental) | Iron overladed brains in the inferior temporal cortex may be involved in accelerated cognitive decline in AD patients. | Human | AD | [135] |
Abbreviations: CORM, CO-releasing molecule; BDNF, brain-derived neurotrophic factor; TrkB, tropomyosin-related kinase B; MCAO, middle cerebral artery occlusion; AMD, age-related macular degeneration; IR, ischemia-reperfusion; TBI, traumatic brain injury; AD, Alzheimer’s disease.