Proteins that are differentially expressed or elevated in tissue and biofluids after central nervous system injuries are described. Elevated or reduced levels of the proteins, alone or in various combinations or ratios, can be used to assess severity of central nervous system injury (CNS injury) including traumatic brain injury (TBI), traumatic spinal cord injury (SCI) and chronic traumatic encephalopathy (CTE). Time course measurements post CNS-injury of these proteins can be used to monitor progress or recovery over periods up to several months. Differentiation of acute, subacute and chronic injury can be diagnosed by comparing the protein levels in CNS-injury patients at days 1-3, day 4-10 with levels at day 30-180 in comparison with normal controls.