Arnold R. Eiser - Preserving Brain Health in a Toxic Age: New Insights from Neuroscience, Integrative Medicine, and Public Health

When and how did our knowledge of neurons, astrocytes, and glial cells begin to emerge? To ponder this evolution of knowledge, we need to turn to a remarkable man, Santiago Ramon y Cajal, born in 1852 in Petilla de Aragon, Navarre, Spain. Cajal was one of the first and foremost neuroscientists in the world and is regarded as a founder of the discipline. Not surprisingly, he was one of the first to consider the structure and functions of neuroglial cells. Cajal was a rebellious youth frequently expelled from school. (He probably would have been diagnosed in todays American schools with attention deficit hyperactivity disorder [ADHD], were he a student here.) Later he displayed skill as an artist and gymnast, but his father first apprenticed him to become a barber and shoemaker. Those efforts failed, as he was certainly ill suited to their repetitive nature. His father had, in the meantime, become an anatomy professor at the University of Zaragoza in Spain and encouraged Cajal to use his artistic talents to sketch anatomical figures and remains. This task resonated with Cajal, and he subsequently agreed to enroll in medical school there. Upon graduation and searching for adventure and some profit, he was recruited as a military physician. At the time, Spain was fighting the Ten Years War in Cuba, putting down the rebellion there. Cajal went off to the war, during which he contracted both tuberculosis and malaria, two life-threatening infections. Fortunately for the future of neuroscience, he remarkably recovered from those illnesses and, upon returning to civilian life, applied his military bonus to the purchase of a microscope. Peering through that scope (and another more refined one with a Zeiss lens provided by the Spanish government), Cajal developed the contiguous neuron theory of the nervous system. This concept holds that neurons communicate with one another while retaining their individual distinctive cell structure. Neuronal cells communicate with one another by forming synapses where electrochemical events build a burgeoning forest of branching communications. His sketches of the microscopic cells were crucial evidence of his theory and were so precise they are still used to educate neuroanatomists and physicians to this day.

Cajal originally hailed from the Aragon region of Spain, where the local character was known for its enduring tenacity. This characteristic, along with his meticulousness and creative imagination, was essential to his path-breaking studies of the nervous system and a prescient understanding of how the nervous system functions. For his efforts, he shared the 1906 Nobel Prize in Physiology and Medicine with the Italian scientist Camille Golgi. Golgi had developed the staining techniques that led to visualizing neurons and other cells of the central nervous system (CNS). Cajal and Golgi had opposing views of how the brain worked, which led to quite an interesting Nobel awards ceremony where conflicting theories were advanced concurrently. Cajal, in keeping with his rebellious character, adopted and modified Golgis method of staining nerve cells that permitted him to peer more precisely into the nervous system. He accomplished this while serving as a professor at the University of Barcelona School of Medicine. (When in Barcelona a few years ago, I visited the historic amphitheater where Cajal lectured during his tenure there.)

Cajal also helped elucidate the physiological function of the astrocyte. He was the first to note that astrocytes played an important mediating role between neurons and the capillary blood vessels needed to maintain brain tissue as viable. The local microcirculation appeared to be physically dependent on astrocytes, and contemporary research in this area has provided further evidence that this is the case.

Another interesting point to note is that during human evolution brain size increased 300 percent from our ape forebears; yet this great increase was accompanied by only a 125 percent increase in the number of neurons. So, a greater number of astrocytes and other glial cells appear to have been important in the development of higher intelligence. Cajal himself must have possessed a great many (healthy) astrocytes to visualize how the brain functions so clearly over a hundred years ago!

I wish to suggest that we need to learn not only the basics of neuroscience from Cajal but also his healthy skepticism of the received wisdom of the academic establishment. If we were merely to adopt the conventional understanding of brain disease, we could be stuck in neutral as our current state of treating and preventing neurological disorders such as dementia and autism.