Neuroimaging of Subacute Brain Inflammation and Microstructural Changes Predicts Long-Term Functional Outcome after Experimental Traumatic Brain Injury

Abstract

There is currently a lack of prognostic biomarkers to predict the different sequelae following traumatic brain injury (TBI). The present study investigated the hypothesis that subacute neuroinflammation and microstructural changes correlate with chronic TBI deficits. Rats were subjected to controlled cortical impact (CCI) injury, sham surgery, or skin incision (naïve). CCI-injured (n = 18) and sham-operated rats (n = 6) underwent positron emission tomography (PET) imaging with the translocator protein 18 kDa (TSPO) radioligand [F]PBR111 and diffusion tensor imaging (DTI) in the subacute phase (≤3 weeks post-injury) to quantify inflammation and microstructural alterations. CCI-injured, sham-operated, and naïve rats (n = 8) underwent behavioral testing in the chronic phase (5.5-10 months post-injury): open field and sucrose preference tests, two one-week video-electroencephalogram (vEEG) monitoring periods, pentylenetetrazole (PTZ) seizure susceptibility tests, and a Morris water maze (MWM) test. In vivo imaging revealed pronounced neuroinflammation, decreased fractional anisotropy, and increased diffusivity in perilesional cortex and ipsilesional hippocampus of CCI-injured rats. Behavioral analysis revealed disinhibition, anhedonia, increased seizure susceptibility, and impaired learning in CCI-injured rats. Subacute TSPO expression and changes in DTI metrics significantly correlated with several chronic deficits (Pearson's |r| = 0.50-0.90). Certain specific PET and DTI parameters had good sensitivity and specificity (area under the receiver operator characteristic [ROC] curve = 0.85-1.00) to distinguish between TBI animals with and without particular behavioral deficits. Depending on the investigated behavioral deficit, PET or DTI data alone, or the combination, could very well predict the variability in functional outcome data (adjusted R = 0.54-1.00). Taken together, both TSPO PET and DTI seem promising prognostic biomarkers to predict different chronic TBI sequelae.

Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway

“…According to previous studies (Sullivan et al, 2003; Missault et al, 2019), the OFT was used to assess anxiety-related behavior and locomotor activity in an open field arena (47 cm × 47 cm × 50 cm). Rats were gently placed in one of the arena’s corners and recorded from the soundproof box, which was illuminated by a red fluorescent light (30 W).…”

Anhedonia following mild traumatic brain injury in rats: A behavioral economic analysis of positive and negative reinforcement

“…14,15 Controlled cortical impact (CCI) injury in Sprague Dawley rats resulted in lower sucrose preference at 1 week and 5.5 months after injury. 12,69 Finally, repetitive closed head injury (2 injuries, 24 hours apart) decreased sucrose preference 2 weeks after injury. 70 In general, reduced sucrose preference was observed after TBI in rodents suggesting anhedonia for positive reinforcement, in line with anhedonia observed in TBI patients.…”

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

“…Notably, the alteration in radial anisotropy displayed the largest effect size and were directly correlated with histological measures of axonal damage (Li et al, 2013 ; Tu et al, 2016 ; also in rat models). FA maps have demonstrated substantial microstructural abnormalities also in case of experimental blast injury in mouse (Rubovitch et al, 2011 ; Hutchinson et al, 2018 ; Venkatasubramanian et al, 2020 ; Weiss et al, 2020 ) as well as in rat models (Budde et al, 2013 ; Begonia et al, 2014 ; Kamnaksh et al, 2014 ; Zhuo et al, 2015 ; Tang et al, 2017 ; Badea et al, 2018 ; Missault et al, 2019 ; Mohamed et al, 2020 ; San Martín Molina et al, 2020 ). DTI appeared sensitive enough to detect changes even in mild TBI models (Hylin et al, 2013 ; Takeuchi et al, 2013 ; Long et al, 2015 ; Li et al, 2016 ; Herrera et al, 2017 ; Kikinis et al, 2017 ; Wendel et al, 2018 ; Hoogenboom et al, 2019 ) and in distant locations within the brain up to 1 year after injury (Pischiutta et al, 2018 ).…”