New Insight into the Mechanism of Neurochemical Imbalance in Multiple Sclerosis: Abnormal Transportation of Brain Extracellular Space.

• DOI: 10.14336/ad.2024.1
• Publication Date: 2025-03-05
• Authors: Yumeng Cheng; Jiao Liu; Tian Feng; Hanbo Tan; Tianyu Wang; Jiabin Lu; Zeqing Tang; Xinlei Ma; Jingge Lian; Shaoyi Su; Yu Fu; Jia Liu; Yuliang Li; Wanyi Fu; Meng Xu; Hongbin Han
• Keywords: Neurochemical; Chemical space

Neurochemical imbalance is a contributing factor to neurological symptoms in multiple sclerosis (MS). The matured myelin sheath crucial for substance transportation within the extracellular space (ECS) and maintaining local homeostasis. Therefore, we hypothesize that disturbed ECS following demyelinating lesions might lead neurochemical MS. In current study, lysophosphatidylcholine-induced unilateral MS model was used investigate spatial alterations. results demonstrated 168 substances were altered around demyelination site ipsilateral hemisphere, compared contralateral with significant enrichment purine arginine-proline metabolic pathways. Notably, dopamine unexpectedly detected demyelinated region adjacent thalamus. Tracer-based MRI further revealed tracer injected into striatum abnormally refluxed thalamus, area of reflux consistent distribution. interstitial fluid drained extensively but confined which may explain observed widespread changes other neuroactive substances. Importantly, after restoration integrity, both drainage imbalance, including dopamine, normalized, supporting potential link between dysfunction imbalance. These observations highlight role transport homeostasis brain, providing new insights mechanisms underline neuropsychiatric