Citation

Harish G, Mahadevan A, Pruthi N, Sreenivasamurthy SK, Puttamallesh VN, Keshava Prasad TS, Shankar SK, Srinivas Bharath MM. J. Neurochem. 2015; 134(1): 156-172.

Affiliation

Departments of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, Karnataka, India.

Copyright

(Copyright © 2015, John Wiley and Sons)

DOI

10.1111/jnc.13082

PMID

25712633

Abstract

Traumatic brain injury (TBI) contributes to fatalities and neurological disabilities worldwide. While primary injury causes immediate damage, secondary events contribute to long-term neurological defects. Contusions (Ct) are primary injuries correlated with poor clinical prognosis, and can expand leading to delayed neurological deterioration. Pericontusion (PC) (penumbra), the region surrounding Ct, can also expand with oedema, increased intracranial pressure, ischemia and poor clinical outcome. Analysis of Ct and PC can therefore assist in understanding the pathobiology of TBI and its management. The current study on human TBI brains noted extensive neuronal, astroglial and inflammatory changes, alterations in mitochondrial, synaptic and oxidative markers and associated proteomic profile, with distinct differences in Ct and PC. While Ct displayed petechial haemorrhages, thrombosis, inflammation, neuronal pyknosis and astrogliosis, PC revealed oedema, vacuolation of neuropil, axonal loss and dystrophic changes. Proteomic analysis demonstrated altered immune response, synaptic and mitochondrial dysfunction, among others, in Ct, while PC displayed altered regulation of neurogenesis and cytoskeletal architecture, among others. TBI brains displayed oxidative damage, glutathione depletion, mitochondrial dysfunction and loss of synaptic proteins, with these changes being more profound in Ct. We suggest that analysis of markers specific to Ct and PC may be valuable in the evaluation of TBI pathobiology and therapeutics. This article is protected by copyright. All rights reserved.

Language: en