Dr. Anne Foerster

The Restorative Brain



Anne Foerster

The star of this story, the brain, is made of pathways of nerve fibers and of collections of nerve cell bodies (neurons) which they pass information to and/or receive information from. Intricate patterns of long nerve fibers, called axons, connect their nerve cells with others, near or far away, where they give information at synapses. The longest thickest ones, that send messages fastest, are surrounded by a fatty compound called myelin that helps them do this. Nerve cells make a lot of protein, to nourish these long axons, and in their cell body is a nucleus with a large nucleolus that helps do this. Neuroglial cells nourish the nerve connections. The pathways are called tracts. The neuronal collections are called nuclei if they are three-dimensional and layers if they are flat. The complicated yet similar architectures of normal brains speak of rigidly organized forces, during development, which make tracts go to their correct targets despite encountering other axons, developing or mature, that are going to other places. The architectures speak of many important things such as behavior, sensation, emotion and memory, since the different pathways transmit different types of useful information.

rat with implanted device

Diagram of rat with cutting device inserted into brain.

The pathways look different. Some are compact, with parallel axons. Axons in other pathways may interweave, both within their pathway or intermixing with other pathways. Axons may all go in one direction, originating from a single set of neurons, or travel in both directions, originating from neurons both at the beginning and end of the pathway. Some pathways contain axons that originate from neurons in the course of their pathway, which follow its entire course to a final destination, stop at neurons on the way there, or make branches and do both.

My scientific life-work, producing evidence about how the brain can heal accurately after injuries that cut it, brings us a new type of appreciation of this soggy, intricately patterned, mass of tissue that we have inside our skulls.

Anne and Mike Holmes at lab 2

Anne Foerster and Michael Holmes in the lab

For many decades, with staining techniques for visualizing nerve fibers in brain sections, the adult brain has been thought of as a pinnacle of intricate organization created again and again during development, in animal after animal. However, after its nerve fibers had been cut, they seemed to show only pathetic and abortive attempts to elongate. When special treatments made them do this, the elongation was sparse. Those axons usually looked abnormal, did unnatural things like growing into implanted tissue, and didn’t get very far.

These results were interpreted as speaking of the perfection of the adult brain, and the hopelessness of its healing spontaneously after it was cut. That was quite a reasonable conclusion since the portion of the severed axon which was still connected to its protein-making cell body, and which would have to navigate successfully to its former target if it grew, would be in a quite a different environment from the one it had encountered in development, and most likely its cell body would not be in an appropriate growth state.

My question was – if the injured brain healed perfectly, and then looked normal, how could we know later on that it had been cut? I developed ways of marking exactly what had been cut, no matter what happened later. Cut axons did grow across these lesions, in an orderly way, and I will write about this in the future. However the most dramatic and informative findings came when I made permanently defined cuts by lowering a fine wire cutting devices through the brains of deeply anesthetized animals, implanting them immediately, and removing them later on, after healing, through the lower surface of the fixed brain. Later on, detours, of the set of axons severed nearest to the ends of the lesions, had developed around these cuts. It always seemed as if the cut pathways had become reconstructed appropriately, in an orderly way very near the lesion, and carried axons that reached their appropriate target. They were myelinated when the severed parent was myelinated. These new architectures speak of creative, reconstructive healing. The axons involved could travel far outside the territory they would have encountered during development, yet they never seemed “lost”.

The ingenuity suggested by these new architectures speaks of the brain as a worthy opponent to traumatic loss, with a lively ability to heal and to take many novel routes to do so. Comparing the beautiful new structures with the beauty of what they looked like before they were cut speaks, without words, of an impressive hope for healing after disaster. They are reminiscent of the myth of the Phoenix.

But do these reconstructed tracts do anything? I asked, in experiments with the cut optic tract of the rat, if it could grow around the lesion and activate the appropriate target – and not only did it do so, it made physiologically normal synapses in the appropriate layer of the target and re-connected the appropriate region of the target with its appropriate region of the retina.

I asked early on, in a pilot study with two adult monkeys at the lab of Dr. Perry Black, if detours could develop around implanted cutting devices in animals more nearly like humans – and they did. Thus, I continued on my research path.

Anne with silk paintings 2005 symposium small copy

A poster session with exhibition of Tambria Higgins Read’s brain paintings

Now I’m excited about making paired pictures of brains that have healed in detours, both as art and as possible encouragement for people with brain damage and their loved ones. Photographs of brain sections, stained for nerve cells and fibers (browns), myelin (normal usually blue-green, degenerate bright blue) and supporting cells (pink) can affect people like art, evoking various impressions. They inspired a “blocked” artist to paint the images on silk so she could stroke them! I want to collaborate with artists and writers, as well as scientists, to help in these descriptions.

I’ve been analyzing the long-term new patterns to see if they can be classified, to help understand what can have produced them and to help interpret the short-term changes than happen. I plan to analyze the short-term results, to see if one factor in the appearance of this new orderliness very near lesions might involve an appropriate re-joining of the severed parts of axons. That wouldn’t be the only explanation, though – there are many enigmatic reconstructive forces generated by that lesion which beg for the designing of exciting new experiments, to interpret what the severed brain is saying about itself when it speaks by generating new architectures!