Regrowing Axons Not Enough To Make Functional New Nerves Interview with:
Zhigang He, PhD, BM 
Professor of Neurology  and
Michela Fagiolini, PhD Assistant Professor of Neurology
F.M. Kirby Neurobiology Center, Department of Neurology
Children’s Hospital, Harvard Medical School
Boston, MA 02115, USA

Medical Research: What is the background for this study?

Drs. Fagiolini and He: Brain or spinal cord injury is still a major medical problem and there is no effective treatment of promoting functional recovery. A key issue is the nerve fibers, or axons, connecting different brain regions are damaged and cannot be repaired. For example, the axons in the optic nerve are the only channels transmitting visual signals from eye to brain. If damaged, our brain will not be able to receive visual signals and be blinded. Thus, a logical therapy should be to stimulate damaged axons to regrow to the targets and reconnect the eyes and brain. Studies in the past from us and others revealed several approaches of promoting the regrowth of injured axons, but it was unknown whether these regenerated axons could form functional connections and mediate functional recovery.

Medical Research: What are the main findings?

Drs. Fagiolini and He:  What we discovered in this study is that these regenerated axons could form functional connections, synapses, in the brain targets, but surprisingly fail to mediate behavioral visual function recovery. In mammals, many long projecting axons are insulated by lipid-enriched myelin sheets which could significantly speed up nerve conduction and facilitate the functional coordination of different brain regions during behavior. Interestingly, we found that different from intact optic nerves, these regenerated axons fail to be myelinated and thus possess poor conductance. When we treat these mice with compounds that can improve nerve conduction, we do observe partial yet significant functional recovery. Thus, there are at least two pieces of information from this study:

  • First, axon regrowth might not enough for functional recovery, nerve conduction could be another hurdle;
  • Second, the combination of these manipulations could serve a proof-of-principle example for achieving functional recovery.

Medical Research: What should clinicians and patients take away from your report?

Drs. Fagiolini and He: These results represent a step forward toward a clinical application yet there is still a significant amount of work needed. Although the compound 4-aminopyridine (4-AP) has been approved for clinical treatment of the patients with multiple sclerosis, it is still unknown whether our manipulation of promoting axon regeneration is effective in humans. Our current efforts are towards identifying novel treatments that could promote the myelination of regenerated axons. It would be exciting to test these and other issues.

Medical Research: What recommendations do you have for future research as a result of this study?

Drs. Fagiolini and He: As mentioned above, in addition to axon regeneration, we also need to pay attention to other steps towards functional recovery. It is not totally surprising, as wiring the brain is the first chapter of neurobiology textbook. Our studies highlight the importance of myelination in this type of functional recovery. Perhaps other post-growth steps such as activity-dependent remodeling could be important for promoting this and other types of functional recovery. Answering these questions might allow us to address important questions about functional recovery, such as what types of function could be restored and to what extents functional recovery is achievable.

Medical Research: Is there anything else you would like to add?

Drs. Fagiolini and He: Our work was the result of a highly collaborative effort across multiple laboratories here at BCH and Harvard University. We believe that this multi-disciplinary approach although complex and expensive has the highest chances to allow the identification of an effective treatment that can be translated into clinical setting


Restoration of Visual Function by Enhancing Conduction in Regenerated Axons
Bei, Fengfeng et al.
Cell , Volume 164 , Issue 1 , 219 – 232

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Zhigang He, PhD, BM and, & Michela Fagiolini, PhD (2016). Regrowing Axons Not Enough To Make Functional New Nerves