New imaging technique: toward spinal cord regeneration?

The axon is a part of the neuron through which nerve impulses are transmitted, and at the end of which is located the synapse, which connects it to another neuron. In the event of a lesion, the axon is the component which must be regenerated in order to restore the connections between the different neurons and re-form the nerve.

The regeneration capacity of axons within the central nervous system, of which the spinal cord is part, has until now been much debated. Axons can regenerate toward the muscles, whereas in the opposite direction inhibiting factors prevent regrowth toward the nerve centers. The observation made by Geneviève Rougon's team at IBDML shows that the axons also regrow in the direction of the spinal cord within a short lapse of time after the injury. Moreover, this regrowth is encouraged by post-traumatic angiogenesis, in other words by the process of formation of new blood vessels in the damaged tissue.

After injury to a mouse's spinal cord, extensive and extremely active angiogenesis is observed, peaking in intensity one week after the lesion. At the same time, regrowth of the axons takes place preferentially and more rapidly in the vicinity of the blood vessels. These observations suggest that stimulating and prolonging angiogenesis could open up new prospects for treatment and encourage functional recovery after, for instance, lesion of the spinal cord.

This spatio-temporal interaction was described by combining two new techniques in imaging: the use of mice whose cell populations can be observed thanks to their fluorescent properties, and 2-photon microscopy. This new imaging protocol makes it possible to display in situ and in 3D the cell phenomena that come into play under traumatic or pathological conditions, and to characterize their dynamics by means of repeated observations of the same mouse. In this way, cell interactions can be described dynamically, over space and time, in a live animal, something that is impossible to do with conventional histology (1) techniques, which require the sacrifice of several animals at each relevant stage. This non-invasive technique drastically reduces the number of mice used and, since the experiment can be reproduced using the same animal, considerably improves the result.

In addition to its importance for fundamental research, such a combination opens up new prospects for preclinical research. In the field of pharmacology, for instance, this kind of dynamic imaging could make it possible to precisely define application protocols for medicines, and better control their effects and adjust dosage.

(1) Histology is the branch of biology which studies tissue.

Full bibliographic information: Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord, PNAS online, 21 May 2009, Cyril Dray, Geneviève Rougon, Franck Debarbieux