Longitudinal neurochemical profiling after experimental stroke using edited MR spectroscopy

Background: Alterations in excitatory and inhibitory neurotransmission contribute to stroke pathology and recovery, yet longitudinal assessment of these changes in vivo remains limited. We investigated the feasibility of longitudinal edited proton magnetic resonance spectroscopy (1H-MRS) to quantify {gamma}-aminobutyric acid (GABA) and glutamate following experimental focal cerebral ischaemia. Methods: Male rats underwent endothelin-1-induced striatal ischaemia or sham surgery. Longitudinal edited 1H-MRS was performed at baseline and 2-, 7- and 30-days post-stroke at 7-tesla with a MEGA-sLASER sequence. A voxel was positioned within the ipsilesional motor cortex adjacent to the lesion. Behavioural outcomes (grip strength, adhesive removal and CatWalk gait analysis) were assessed alongside spectroscopy, and immunohistochemistry for Iba1, GFAP and ICAM-1 was performed at 30 days. Results: Stroke induced a transient reduction in GABA+/tCr within the ipsilesional motor cortex, with significantly lower concentrations than sham animals at 7 days (p<0.05), returning to baseline by 30 days. Glutamate/tCr and GABA/glutamate ratio were unchanged throughout the study. Behavioural deficits were mild, with significant effects on motor outcomes such as grip strength, gait swing speed and paw placement, while sensory areas of the brain seemed largely unaffected. Histological analysis revealed no persistent differences in cortical Iba1, GFAP or ICAM-1 immunoreactivity at 30 days. Conclusions: Longitudinal 1H-MRS is a feasible approach for monitoring dynamic changes in inhibitory neurochemistry following experimental stroke. The transient reduction in peri-lesional GABA, despite minimal behavioural impairment and an absence of persistent cortical inflammation, supports the use of edited spectroscopy as a translational tool to investigate neurochemical mechanisms underlying network dynamics in post-stroke recovery.