Table 1.
In vivo studies showing the anti-inflammatory action of Ang-(1–7) in the brain.
| Reference | Pathology | Species | Treatment | Neuroinflammation | Functional outcome | Other findings |
|---|---|---|---|---|---|---|
| Hoyer‐Kimura et al. (124) | Cognitive impairment | mouse | glycosylated Ang-(1–7) (PNA5), 50–500 μg/kg subcutaneously injected for 24 d | ↓ pro-inflammatory cytokine (TNF-α) ↑cytokines (IL-1α, IL-2, IL-5, IL-13, IL-17, IL-10) | ↑ memory | ↓ NfL (both with Ang-(1–7) and PNA5) |
| Rabie et al. (125) | Parkinson’s disease |
rat | Ang-(1–7), 240 pg daily injected into the striatum for 1 w | ↓ pro-inflammatory markers (RAGE and HMGB-1, NF-κB, p65 TNF-α, PARP-1) | ↑ motor performance | rescue of dopaminergic neurons |
| Arroja et al. (126) | Stroke | rat | Ang-(1–7), 1 nmol/h intracerebroventricular infusion with osmotic pump for 6 w | no effect | ↓ tissue damage ↑ BBB damage ↑Nox1 |
|
| Cao et al. (127) | Alzheimer’s disease | mouse | Ang-(1–7), 400 ng/kg/min, with osmotic minipump for 4 w | ↓ microgliosis (CD68, IBA1) | ↑ memory | ↓ amyloid deposits ↑ neuronal count |
| Hay et al. (128) | Cognitive impairment | rat | glycosylated Ang-(1–7) (PNA5), 1.0 mg/kg subcutaneously for 21 d | ↓ microglial activation (IBA1) ↓ pro-inflammatory cytokines (TNF-α, IL-7) ↑anti-inflammatory cytokine (IL 10) |
↑ memory | PNA5: ↑ blood-brain permeability ↑ stability/bioavailability ↓ ROS |
| Janatpour et al. (129) | TBI | mouse | Ang-(1–7), 1 mg/kg s.c. by osmotic pumps 1 or 6 h post-injury, until 3 or 29 d. | ↓ astrogliosis (GFAP) ↓ microgliosis (IBA1) |
↑ learning and memory ↑ motor |
↓ lesion volume ↓ neuronal death ↓ vessel density |
| Regenhardt et al. (66) | Stroke | rat | Ang-(1–7), 100 pg intracerebroventricular infusion with osmotic pump for 6 w | ↓ microgliosis (IBA1) ↓ pro-inflammatory cytokines (IL-1α, IL-6) |
↑ lethargy | ↑ survival ↓ brain hemorrhages |
| Regenhardt et al. (120) | Stroke | rat | Ang-(1–7), 1.1 nM; 0.5 μl/h in the brain by osmotic pumps | ↓ microgliosis (IBA1) | ||
| Rabie et al. (130) | Parkinson’s disease | rat | Ang-(1–7), 240 pg daily injected into the striatum for 1 w | ↓ pro-inflammatory markers (p-MAPK p38/NF-κB p65) | ↑ motor performance | |
| Hay et al. (131) | Heart failure | mouse | Ang-(1–7), 500 pg/kg/h s.c. by osmotic pump for 4 w | ↑ neuroprotection markers (CXCL12, CXCL13,G-CSF,CCL2,IL-16,IP-10,sICAM and IL-1ra) | ↑ memory | |
| Goldstein et al. (132) | Brain damage by Shiga toxin | rat | Ang-(1–7), 200 pg daily injected into the hypothalamic area for 8 d | ↓ microglial cell number ↓ astrocytic damage |
↓ neuronal damage ↓ demyelination |
|
| Bihl et al. (133) | Stroke | mouse | Ang-(1–7) (240 pg/kg/h) minipump infusion | ↓ pro-inflammatory markers (TNF-α, MCP-1, IL-8, NF-κB) | ↓ sensorimotor deficits | ↑ vascular remodeling ↓ hemorrhage volume |