Ramesh Raghupathi, PhD

Dr. Raghupathi is a professor in the Department of Neurobiology & Anatomy at Drexel University College of Medicine. He did postdoctoral training at the University of Connecticut Health Science Center and the University of Pennsylvania School of Medicine. Before coming to the College of Medicine in 2003, he served on the faculty in the Department of Neurosurgery at the University of Pennsylvania School of Medicine. 


Cell death and plasticity after traumatic injury to the mature and immature brain


The spectrum of traumatic brain injuries ranges from mild concussions that are treated in the emergency room, to severe head injuries that require acute critical and neurosurgical care. Improved critical and advanced radiological and neurosurgical techniques have led to decreases in mortality rates over the past two decades. However, survivors of brain injuries suffer long-term behavioral problems such as learning deficits, memory dysfunction, psychological and emotional disturbances – functional aspects that affect the quality of life and currently have no therapies. The economic costs of traumatic brain injuries, which include hospitalization, health care and lost work hours, is estimated at almost $35 billion. This problem has become particularly relevant in the past decade, with the Iraq war veterans returning home having suffered blast-related concussions, injuries that are poorly understood. It is estimated that several thousand soldiers have suffered head injuries since March 2003.

The damage observed after TBI comprises both primary disruption of neural tissue related to the impact, and secondary mechanisms that develop over the weeks to months after the traumatic event. The spectrum of pathologies observed after TBI include focal contusions in the grey matter and diffuse injuries to axons in the white matter. It has been suggested that these pathologies are a consequence of the biomechanics of the impact, i.e., focal injuries occur due to contact forces to the head, while diffuse injuries are a result of non-contact, rotational forces to the brain. While aspects of focal pathology can be superimposed on diffuse brain injury (and vice versa), it is our belief that significant differences exist between the pathobiology of these two types of injuries that warrant the separate evaluation of mechanisms of damage in the cell body (soma) and the axon. Secondary mechanisms of neural damage are initiated immediately after impact and result in a number of cascades that affect both the neural tissue and the vasculature. In response to the impact, the brain becomes edematous leading to increases in intracranial pressure and subsequent neuronal death, which may be an underlying cause for the neurologic impairment. In turn, injured neurons are faced with imbalances in ionic homeostasis, over-activation of excitatory amino acid receptors, increases in intracellular calcium, increased free radical generation, and mitochondrial dysfunction that may underlie the eventual death of injured neurons. Concomitant with neuronal death and damage, axons are also subjected to mechanical forces that lead to traumatic axonal injury. Injury to axons is characterized by focal accumulations of cytoskeletal proteins resulting in a swollen phenotype in the acute post-traumatic period. Over time these swollen axons undergo complete axotomy (Wallerian degeneration), a process that is associated with death of oligodendrocytes.