Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese‐enhanced MRI (MEMRI)

Abstract

Purpose: To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species. Materials and Methods:The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl 2 injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONCþPNG; rats) or lens injury (ONCþLI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl).Results: Signal intensity profiles of the Mn 2þ -enhanced ON were consistent with ON regeneration in the ONCþPNG and ONCþLI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn 2þ -enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration.Conclusion: Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species.

Manganese enhanced MRI (MEMRI): neurophysiological applications

“…As summarized here, MEMRI allows for relatively fast, noninvasive, longitudinal and in vivo imaging in many different animal models ranging from small amphibians, such as frogs to non-human primates, such as rhesus monkeys. It can be administered by various means, intranasally via lavage (Pautler et al, 1998; Smith et al, 2007), optically via injections into the vitreous (Pautler et al, 1998; Sandvig et al, 2011), intracerebrally via stereotaxic injections (Van der Linden et al, 2002; Saleem et al, 2002; Pautler et al, 2003; Watanabe et al, 2004) etc. to allow for the visualization of different pathways within the nervous system.…”

“…As a result, signal enhancement was not seen in the retinal projection until 48 h in frogs and 96 h in fish after intra vit injection of Mn 2+ . They were able to demonstrate also, that MEMRI could be utilized for long-term monitoring and assessment of nerve regeneration in rodents as well as fish and frogs (Sandvig et al, 2011). …”

“…Sandvig et al also utilized MEMRI as a tract tracer to assess the integrity of regenerating fibers within mice, rats, frogs and fish (Sandvig et al, 2011). Lower vertebrates, such as frogs and fish have been known to spontaneously regenerate injured nerve fibers.…”

“…[Reproduced from Sandvig et al (2011). Copyright © 2003 John Wiley & Sons, Inc. Reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.]…”

Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain

“…Studies have shown that brain activities that took place days before imaging tests could be detected using appropriate Mn 2+ administration schemes such as implanted osmotic pump infusion (9, 10). The long Mn 2+ brain retention time also enables the monitoring of Mn 2+ axonal transportation for studies evaluating neural pathways (11–13). MEMRI is also proven a valuable tool in neurodegenerative disorder studies using rodents (14–25).…”