We investigated Manganese Enhanced MRI (MEMRI) abilities to detect glial (astrocyte and microglia) and neuronal activation signals following treatment with known inflammatory inducing agents. The idea is to distinguish between gliosis (glial activation) and neuronal injury for the MEMRI signal and as such use the agent as a marker for neural activity in inflammatory and degenerative disease. We demonstrated that glial inflammation facilitates Mn2+ neuronal ion uptake. Glial Mn2+ content was not linked to its activation. MEMRI performed on mice injected intracranially with lipopolysaccharide was associated with increased neuronal activity. These results support the notion that MEMRI reflects neuronal excitotoxicity and impairment that can occur through a range of insults including neuroinflammation.
T1-wt images and enhancement quantification.
a) T1-wt image of a LPS + MnCl2 mouse. Areas around the injection line were encased by red boxes and shown in magnified windows. b) T1-wt image of a PBS + MnCl2 mouse. c) Enhancement measurements. The LPS + MnCl2 group showed significantly higher signal enhancement than the PBS + MnCl2 group (p < 0.01). d) Enhanced volume. The LPS + MnCl2 group showed significantly larger enhanced volumes (p < 0.01). e) T1-wt image of a LPS only (no MnCl2 injection) mouse. No obvious signal enhancement was observed in the mice injected with only LPS but not MnCl2.
Immunohistology. a) A brain section of a LPS + MnCl2 mouse at Day 1 after LPS injection. The reactive microglia by Iba-1 in the regions encased in red boxes about the injection line are shown at 20×. b) A brain section of a LPS + MnCl2 mouse (top row) and of a PBS + MnCl2 mouse (2nd row). The reactive astrocytes by GFAP and microglia by Iba-1 in the regions encased in red boxes around the injection line are shown at 20×. c) Glial reactivity quantification.
Astrocytic and microglial reactivity represented by GFAP and IBa-1 expressions (Intensity/μm2) were significantly higher in the LPS + MnCl2 group compared to the PBS + MnCl2 group (p < 0.01 and p < 0.05, respectively)
For further information, see:
Bade AN, Zhou B, Epstein AA, Gorantla S, Poluektova LY, Luo J, Gendelman HE, Boska MD, Liu Y. Improved visualization of neuronal in jury following glial activation by manganese enhanced MRI. J Neuroimmune Pharmacol. 2013 Sep;8(4):1027-36.