Non-Invasive Assessment of Acute Neuroinflammation and Demyelination after Spinal Cord Injury in Young and Aged Rodent Models Using Positron Emission Tomography

Abstract

According to the Global Burden of Disease Study 2019, there were approximately 0.9 million new cases of spinal cord injury worldwide. Injury to the spinal cord can lead to significant and often permanent loss of sensory and motor functions. The impairment of sensory and motor functions is a consequence of cellular and molecular events triggered by the injury, resulting in secondary complications. Inflammation and demyelination are two of the primary pathological processes that occur after SCI. Research suggests that these secondary complications are exacerbated in the aged population. This study aimed to assess neuroinflammation and demyelination in a rat model of SCI, comparing young and aged rats using non-invasive positron emission tomography/computed tomography (Positron Emission Tomography (PET)/CT) imaging. Young (3 months) and middle-aged (12 months) male Sprague-Dawley rats were imaged dynamically using inflammation ([¹⁸F]DPA714) and demyelination (3[¹⁸F]F4AP) PET tracers prior to injury and acutely after a moderate contusion T9 SCI. The tracer uptake was assessed by drawing a volume of interest (VOI), and the mean Standardized Uptake Value (SUV_mean) was compared from baseline to post-injury time point for the two radiotracers. Alterations in the tracer SUV_mean were also evaluated between the aged and young animals. Kinetic PET scans demonstrated that both injury and age altered the uptake patterns for demyelination and inflammation PET tracers. Compared to young animals, the aged animals showed increased tracer uptake at the injury site for the inflammation ([¹⁸F]DPA714) marker only. No change in tracer uptake was observed in the uninjured regions distal to the injury site or baseline scans between age groups. Combined PET scans with histological analyses demonstrated that [¹⁸F]DPA714 significantly correlated with gliosis, whereas 3[¹⁸F]F4AP correlates with neuronal and white matter markers. The PET/CT imaging using these tracers has the potential to offer valuable insights into prognosis and treatment effectiveness following SCI.