Abstract: The invention relies on detection of specific identified proteins, protein breakdown products, and peptide fragments, to diagnose and evaluate traumatic brain injury, spinal cord injury, and any traumatic injury to the CNS in a subject. These analytes (proteins, protein breakdown products thereof, and peptide fragments thereof) are released from injured tissue into blood and/or cerebrospinal fluid, and can be used to identify the central nervous system cell types (i.e. neuron, astrocyte, oligodendrocyte, and the like) or subcellular structure (e.g., axon, dendrites, presynaptic terminal, post-synaptic terminal, and extracellular matrix) affected, and to determine the diagnosis, location, and severity of the injury. Time course measurements of these analytes measured at different times after an injury or suspected injury also are used as tools for diagnosis and prognosis of central nervous system injury.