title: Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion.
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 edema, 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. This 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 hemorrhages, thrombosis, inflammation, neuronal pyknosis, and astrogliosis, PC revealed edema, 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. We have characterized the primary injury in human traumatic brain injury (TBI). Contusions (Ct) - the injury core displayed hemorrhages, inflammation, and astrogliosis, while the surrounding pericontusion (PC) revealed edema, vacuolation, microglial activation, axonal loss, and dystrophy. Proteomic analysis demonstrated altered immune response, synaptic and mitochondrial dysfunction in Ct, and altered regulation of neurogenesis and cytoskeletal architecture in PC. Ct displayed more oxidative damage, mitochondrial, and synaptic dysfunction compared to PC.
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
authors.forename: Gangadharappa
authors.initials: G
authors.lastname: Harish
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Mahadevan
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
authors.forename: Nupur
authors.initials: N
authors.lastname: Pruthi
authors.affiliation: Institute of Bioinformatics, Whitefield, Bangalore, Karnataka, India.|Manipal University, Manipal, India.
authors.forename: Sreelakshmi K
authors.initials: SK
authors.lastname: Sreenivasamurthy
authors.affiliation: Institute of Bioinformatics, Whitefield, Bangalore, Karnataka, India.
authors.forename: Vinuth N
authors.initials: VN
authors.lastname: Puttamallesh
authors.affiliation: Institute of Bioinformatics, Whitefield, Bangalore, Karnataka, India.
authors.forename: Thottethodi Subrahmanya
authors.initials: TS
authors.lastname: Keshava Prasad
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
authors.forename: Susarla Krishna
authors.initials: SK
authors.lastname: Shankar
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
authors.forename: Muchukunte Mukunda
authors.initials: MM
authors.lastname: Srinivas Bharath
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003288:Contusions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D040901:Proteomics / Q000379:methods
keywords: human brain; mitochondria; neurotrauma; oxidative stress; proteomics; synaptic terminal