Since the 1970s, TBI has been divided into “primary” and “secondary” brain injuries. The primary injury is the immediate result of energy dissipation within the substance of the brain, and occurs within milliseconds of impact. Primary injuries include direct neuronal, glial, and vascular disruption. Primary injuries are considered irreversible. Secondary injuries are the result of the reactive biochemical events that occur after the primary injury. Some of these reactive biochemical events may accelerate or exacerbate initial cellular injury or cause “new” injury. Current TBI clinical management strategies are designed to minimize secondary injury. The current treatment paradigm is focused on the evacuation of extra-axial fluid collection(s), and the management of cerebral hemodynamics by reducing intracranial pressure (ICP) or increasing arterial pressure (MAP) to optimize cerebral perfusion pressure (CPP).
There are some variations in the precise techniques used to manage these variables, but there is no effect on reversing the primary injury. Clinically, secondary brain injury associated with TBI is caused by the effects of neuro-inflammation, increased blood brain barrier (BBB) permeability and the subsequent cerebral edema, leading to an increase in ICP and a subsequent decrease in cerebral perfusion; if poorly controlled, it will exacerbate the primary injury and increase mortality. It is unlikely that significant advances in reducing the functional disability (motor, cognitive, and behavioral) associated with TBI will be made using the current management strategies alone. Currently, there is no effective treatment to prevent secondary brain injury after TBI. Cellvation is advancing an autologous cellular therapy program for the treatment of severe traumatic brain (closed head) injury in adults and pediatric patients.