On neuronal health

Abstract

Many recent studies of the degeneration, neuroprotection and regeneration of CNS neurons have departed from previous dichotomous descriptions of neurons as either dead or alive. In this brief article aspects of neuronal health are examined by outlining ways to assess both neuronal resilience and vulnerability to common forms of structural brain insults. According to this theory of neuronal health, neurons exist in a dynamic equilibrium that spans a spectrum of cellular existence, constantly influenced by both extracellular physiological changes and intracellular mechanisms designed to react to external stimuli while maintaining structural integrity. The spectrum between particularly resilient and vulnerable neuronal states is illustrated by experiments in vivo that examine trophic and metabolic fluctuations influencing the likelihood of neuronal death after neuronal insults. Studies show that adult CNS neurons can be protected in vivo by trophic agents or other pharmacological interventions against structural and toxic damage. Conversely, low-level neuronal impairment due to genetic or physiological perturbations can predispose neurons to demise by insults that normally would not cause cell death. The experimental approaches described may help in the study of neuronal pathophysiology, and in investigations towards new treatments for the neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease.