title: Longitudinal changes in the DTI measures, anti-GFAP expression and levels of serum inflammatory cytokines following mild traumatic brain injury.
abstract: The majority of human mild traumatic brain injuries (mTBI; 70%) lack radiological evidence of injury, yet may present long term cognitive, and behavioral dysfunctions. With the hypothesis of evident damaged neural tissue and immunological consequences during acute phase of mTBI, we used closed skull weight-drop TBI model to address human mTBI condition. Serum cytokines (TNF-α, IL-10) and glial fibrillary acidic protein (GFAP) expression were examined at day 0 (control, pre-injury), 4h, day 1, day 3 and day 5 post injury (PI). Diffusion tensor imaging (DTI) was performed at similar timepoints to identify neuroinflammation translation into imaging abnormalities and monitor injury progression. DTI indices including mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy and axial diffusivity values were quantified from cortex (CTX), hippocampus and corpus callosum regions. One way ANOVA showed significant increase in TNF-α at 4h and IL-10 at day 1 PI as compared to control. GFAP(+) cells were significantly increased at day 3 and day 5 as compared to control in CTX. Repeated measures ANOVA revealed significant decreases in MD, RD values in CTX at day 3 and day 5 as compared to day 0. A significant, inverse correlation was observed between cortical MD (r=-0.74, p=0.01), AD (r=-0.60, p=0.03) and RD (r=-0.72, p=0.01) values with mean GFAP(+) cells in the cortical region. These findings suggest that mTBI leads to elevated cytokine expression and subsequent hypertrophy of astrocytic processes. The increased numbers of reactive glial cells contribute diffusion restrictions in the CNS leading to reduced MD and RD values. These findings are in line with the deficits and pathologies associated with clinical mTBI, and support the use of mTBI model to address pathology and therapeutic options.
authors.affiliation: NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Singh
authors.affiliation: NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India. Electronic address: triricha@gmail.com.
authors.forename: Richa
authors.initials: R
authors.lastname: Trivedi
authors.affiliation: NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: M Memita
authors.initials: MM
authors.lastname: Devi
authors.affiliation: NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Tripathi
authors.affiliation: NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Khushu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000097:blood* / Q000473:pathology*; D016207:Cytokines / Q000097:blood*; D056324:Diffusion Tensor Imaging / Q000639:trends*; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein
keywords: Cortex; Diffusion tensor imaging; Glial fibrillary acidic protein; IL-10; Mean diffusivity; Mild traumatic brain injury; Radial diffusivity; TNF-α