Low‐Molecular‐Weight Angelica sinensis Polysaccharide Improves Neurological Function and Neuroplasticity Following Cerebral Ischemia–Reperfusion Injury

Neuroplasticity plays a pivotal role in post‐stroke recovery, and Angelica sinensis polysaccharide has demonstrated neuroprotective properties. This study investigated the neuroprotective effects of low‐molecular‐weight Angelica sinensis polysaccharide (LMW‐ASP) in a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Structural characterization revealed that LMW‐ASP (3.9 kDa), containing a pyranose ring and uronic acid, was a heteropolysaccharide that comprised fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid (0.007:0.003:0.057:0.209:0.009:0.284:0.303:0.006:0.032:0.083:0.007). Post‐stroke administration of LMW‐ASP (50 mg/kg) significantly improved body weight and neurological functions after MCAO/R. Moreover, microtubule‐associated protein‐2 expression was notably higher in the LMW‐ASP group than in the model group ( p < 0.01). Furthermore, Golgi‐Cox staining confirmed that LMW‐ASP increased the number of dendritic intersections ( p < 0.05 for 90–120, 180, and 200 μm; p < 0.001 for 70 and 80 μm), the number of terminal branches ( p < 0.01), the number of branch points ( p < 0.01), and the density of basal dendritic spines ( p < 0.05). Finally, transmission electron microscopy revealed an increase in the number of synapses ( p < 0.001) and presynaptic vesicles ( p < 0.001) in the LMW‐ASP group. These results suggest that LMW‐ASP is a potential pharmaceutical therapeutic approach for stroke recovery that enhances neuroplasticity.