Cajal´s dictum that "everything may die, nothing may be regenerated" has had a lasting influence on neuroscience.  The desire to understand the structure and function of the nervous system in exquisite detail has inspired many generations of neuroscientists over the last two centuries.  Their inspiration and hard work has transformed neuroscience into a highly regarded scientific enterprise which has made many contributions to our understanding of the natural world at a breathtaking pace.  While a superordinate goal of neuroscience research is to enhance our knowledge about nervous system structure and function, if one were to ask neuroscientists why they are engaged in research, many would state that
their final goal is to eventually find new therapeutic strategies to reduce the suffering of patients afflicted with neurological disorders such as Alzheimer's Disease, Parkinson's Disease, spinal cord, head injury, multiple sclerosis or blindness.

While a major mission of neuroscience is to develop approaches to the treatment of brain and spinal cord injury and while many papers are regularly published on the subject, there had been no neuroscience journal prior to 1989 that offers a communication forum specifically dedicated to nervous system restoration and repair.  Therefore, with vision and enthusiasm Dr. Donald G. Stein in 1989 founded RNN, an international and interdisciplinary journal. This was a logical next step after the topic of nervous system restoration and recovery had been introduced and became a matter of serious interest about one decade earlier.

By the time RNN was founded in 1989, the public had developed a deep interest in the neurosciences, and the announcement that the 1990's would be the "Decade of the Brain" was a highly effective way to show the growing stature of neuroscience in the larger community. Indeed, the public's interest is well-placed; the last two decades have demonstrated the enormous capacity of the central nervous system to repair itself after injury and paved the way towards finding new therapeutic strategies.  With regard to the issue of brain restoration, transplantation of neuronal tissue and the application of trophic factors in particular were proposed as new therapies for CNS disorders.  Today we not only have important new insights into the healing capacities of the brain and spinal cord but novel, innovative and effective therapeutic strategies are now being developed for human application. At least some have already found their way to routine clinical application.

Several hallmark developments contributed to our current understanding of neuroplasticity which, over the years, led to a paradigm shift:  (a) the observation of recovery of behavioral functions after various types of brain injury, (b) the discovery of axonal sprouting and regeneration of adult neurons when favorable conditions are created, (c) the development of the neuronal transplantation techniques which led to structural and functional repair and  (d) the discovery of nerve growth factor which not only led to the Nobel Prize award to Rita Levi-Montalcini and Stanley Cohen but it has inspired the pharmaceutical industry to search for new drugs.

The scope of the journal is to foster the development and evaluation of innovative therapeutic interventions for the treatment and cure of CNS disorders through a better understanding of neurological diseases and endogenous "repair" mechanisms. By emphasizing behavioral outcome measures, the journal´s manuscript policy is directed toward clinical application and behavioral research. In addition, molecular and anatomical research directly related to the subject matter will be included as this type of study has informed our efforts to describe and understand restoration of brain functions on a cellular and molecular level in recent years.

To get a feeling for the scope of RNN, several newly emerging fields of scientific inquiry can be cited:  For example, studies of brain and spinal cord-injured animals show that there is a remarkable degree of spontaneous recovery of function within days and weeks following the injury, and we need to better understand the neurobiological basis of this recovery process.  New therapeutic approaches such as brain tissue transplantation and neuroprotective agents have also been developed in animal models of stroke and neurotrauma and they have subsequently been tested in human beings, though with limited clinical benefit so far. Also, axonal regeneration has been observed in the mammalian CNS, and by investigating the role of growth enhancing and growth inhibiting factors new therapeutic strategies are being pursued.  It is also known that there are different ways in which cells may die in the nervous system, necrosis and apoptosis. Through a better understanding of the molecular and biochemical basis of cell death, novel neuroprotective agents will be found. Most notably, agents acting on glutamate-mediated neurotoxicity have become known in the last decade.  It is increasingly evident that the neuropathology of cell death and diffuse axon loss following brain injury is rather complex and interactions with the immune system will also have to be considered in more detail. These are just a few examples of basic research suitable for publication in RNN, but there are many more as well.

In the clinical setting, the standard approach to "restore functions" today is the replacement of lost neurotransmitters or manipulating their receptors as exemplified by the L-DOPA treatment in Parkinson´s Disease. In recent years this strategy has been supplemented by efforts to block the self-destruction of nervous system tissue and to enhance the function of surviving neurons.  Observations of reorganization of functions in the injured brains of animals and humans provides a new theoretical basis for brain restoration. Rehabilitation efforts will increasingly make use of well proven training protocols for the treatment of behavioral functions such as locomotion, memory or vision. Thus, therapeutic strategies for neurological disorders may either favorably manipulate the neuropathological cascade of injury, promote better use of residual structures and functions, or take advantage of true "restoration"-potential as best shown by studies of neuronal sprouting and regeneration.

In the 1970s, when Donald Stein proposed that deficits after brain injury can recover, few investigators believed it.  At that time, the idea appeared too far removed from the generally accepted notion of neuronal specificity and a rigid structure-function theoretical framework.  What appeared then to merely be a "curiosity" can almost be considered main stream neuroscience today.

The mission of RNN is to offer a forum of communication for all those interested in the field of brain restoration and plasticity. RNN plans not only to publish original research contributions but it will also include review papers and commentaries. As most papers in brain restoration are usually published in general neuroscience journals (such as European J. of Neuroscience, J. Neuroscience, Neuroscience, Neuron etc.), RNN fills an important niche that is directly relevant to the clinical sciences.

RNN is currently the only neuroscience journal that covers the variety of subjects that share as their common goal the development of strategies to facilitate recovery from CNS injury. It is hoped that through a better understanding of the underlying pathology and the empirical testing of new therapies, opportunities may be found to alleviate the suffering that
results from diseases of the brain and spinal cord. By exploring the frontiers of central nervous system functions and its response to injury, disorders such as Alzheimer´s and Parkinson´s Disease, stroke and traumatic brain injury, multiple sclerosis and paralysis following spinal cord injury, to name just a few, may be treated in novel, more effective ways. RNN has the goal to promote and support this research effort.

It is expected that the investigation of brain plasticity and repair will gain increasing importance and acceptance in the neurological and psychiatric sciences. The aim of RNN is to create a visible focus in this field of neuroscience and I am pleased to say that many of the most distinguished scholars in neuroplasticity research have agreed to contribute to this effort as members of the editorial board of RNN.  Through a joint effort, we will be able to accomplish an important and honorable scientific task:  to help the field of nervous system restoration move forward.  In so doing, we hope ultimately to help alleviate the suffering of patients with brain or spinal cord injury and help them to look forward to a more optimistic future.
 

Bernhard A. Sabel, PhD                                       April , 1999
Editor-in-Chief
University of Magdeburg, Germany and
Princeton University, USA

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