Brain vulnerability and its modulation

Clinical and experimental studies revealed that the injured brain is highly vulnerable to a subsequent insult. Surfery of the literature pertinent to clinical and experimental traumatic brain injury (TBI) is made. Increased vulnerability of the traumatically injured brain to an additional sub lethal ischemic, hypoxic, excitotoxic, or mechanical insult has been clearly demonstrated. Compared to traumatic brain injury alone, the double insult paradigm dramatically increases the brain damage. Brain vulnerability following TBI can be explained by a reduced ability to compensate for a reduction of cerebral blood flow (CBF) and oxygen (O(2)) delivery to the brain or inability to meet an increased metabolic demand. In addition, there is a specific increased sensitivity to delayed insults induced by the first injury. Potential mechanisms of the increased sensitivity to a second insult might be related to post-traumatic gene expression alterations leading to changes in neurotransmitters release, density of receptors and reduced thresholds for activation of pathways leading to delayed cell death. The brain is vulnerable to repetitive injuries. Derangements of compensatory mechanisms are responsible, in part, for this vulnerability. Additional work is needed to better understand the molecular pathways leading to secondary damage and to find novel therapeutic strategies to modulate the brain response to TBI.