Neuroinflammation

Excerpt

Traumatic brain injury (TBI) is the leading cause of death among young people and the elderly in the developed world, and results mainly from falls, violence, and road accidents. Across Europe the incidence of TBI is approximately 235/100,000. While many people recover fully from TBI, many others are left with significant mental, behavioral, and motor deficits, and an estimated figure for people living with ongoing effects from a TBI in Europe is over 7 million. In the United States alone, approximately 1.7 million people suffer a TBI each year, with 275,000 being hospitalized and 52,000 cases resulting in death.

Clinically, TBIs are classified as being mild, moderate, or severe. These classifications are commonly arrived at by means of the Glasgow Coma Scale (GCS), which measures eye response (1–4 points), verbal response (1–5 points), and motor response (1–6 points). A combined GCS of ≥13 indicates a mild TBI, GCS of 9–12 indicates a moderate TBI, and a GCS of <9 indicates a severe TBI. Other scales are occasionally used however, including the Abbreviated Injury Scale, Injury Severity Score, and the length of Post-Traumatic Amnesia.

The types of damage acquired in TBI can be separated into primary and secondary effects. Primary effects are acquired nearly instantly in a TBI as a direct result of damage due to contact or acceleration/deceleration injury, and these can include leaky ion channels, membrane microporation, conformational changes in proteins, and shearing of blood vessels causing hemorrhage. Secondary effects, meanwhile, lie downstream of these primary effects and begin within minutes or hours of the primary insult, and these effects and their underlying molecular pathobiology are all targets for potential treatments for TBI. They include mitochondrial and subsequent energy production impairment, immune cell infiltration and activation, cytokine release, edema formation and resultant increase in intracranial pressure, and apoptosis.,