A Path to Development or Demise ?

Kenneth      Maiese

Abstract

Early reports in the lay literature describe individuals that suffer severe brain injury, but later are able to resume either previously lost cognitive function or motor function of paralyzed limbs. For example, in The Count of Monte- Cristo, the character Monsieur Noirtier de Villefort was reported to have suffered an incomplete injury to the brain, but subsequently was able to communicate by blinking with vertical eye movements. Reports of partial recovery from incomplete lesions to the brain later began to surface in the medical literature. In 1947, the first published case described a patient with an infarction in the territory of the vertebral-basilar artery system who became tetraplegic, was without speech, but regained consciousness. Reports such as this are consistent with a "de-efferented" lesion occurring in the brainstem, usually at the level of the pons that allows cortical function to remain unimpaired, but leads to quadriplegia. In the purest sense, individuals with these presentations are considered to suffer from a "locked-in" syndrome. Yet, other reports that include the present literature describe patients with a variety of nervous system disabilities that may be exclusive of the brainstem, but these patients achieve partial or full recovery from their brain insults raising the question whether the brain is able to repair itself. As a result, it becomes essential to understand the underlying pathology that may determine an individual patients prognosis. The etiology of the initial insult will more often than not determine the overall prognosis of the patient. For example, transient ischemic insults in the vertebral-basilar artery distribution have been reported to lead to a complete resolution of all deficits within twenty-four hours after the initial onset of vascular occlusion. In contrast, aggressive disease processes, such as malignant neoplasms that involve the posterior fossa and the pons, ultimately may lead to the demise of the patient. Yet, evaluation of a patients ability to recover from a nervous system injury should also be considered at the cellular level. If one examines cells that are able to regenerate and proliferate, they must be able to enter and execute a normal cell cycle. However, as we acquire further knowledge of each cells ability to enter the cell cycle during different times in its development or maturation, it becomes evident that not all cells, at least in the final stages of development, should attempt cellular pathways leading to cell cycle induction. Aberrant cell cycle induction, such as with post-mitotic neurons, can ultimately lead to the death of the cell. In this issue of Current Neurovascular Research, we present several investigations that provide insight into common cellular pathways that can serve to foster opposing outcomes in a cell during either normal physiological processes or during acute toxic insults. In particular, some of the studies address the necessary role of new cell growth and cell cycle induction for tissue repair while other studies provide an alternative perspective on cell cycle induction describing cellular pathways that utilize a "dysfunctional" cell cycle to lead to apoptotic cell destruction. In their original article, Popa-Wagner et al. employed experimental focal cerebral ischemia models in both young and aged rats and assessed cell cycle induction, cell growth, and proliferation in the brains of these animals. They report that aged rats have nestin-positive cells in the region of the brain infarct as well as an early incorporation of nestin-positive cells into the glial scar region. Moreover, the capillaries of the corpus callosum were the principal source of proliferating nestin-positive cells, but surprisingly, these cells did not significantly contribute to new neuronal cell formation in the infracted cortex of the aged rats. They hypothesize that blocked migration of these cells may produce the limited neurogenesis response, but postulate that further understanding of the active capillary proliferation response in these aged animals may be applicable to neurodegenerative diseases in the elderly. Interestingly in our next article, Ding et al. note a significant vascular response also in aged rats with new cell proliferation in the brain, but with a novel twist. Angiogenesis in the cerebral cortex was documented during a monitored exercise protocol with a significant upregulation of vascular endothelial growth factor protein, providing.........