BackgroundPlant polysaccharides possess significant anticonvulsant potential. This study investigated the neuroprotective effects of polysaccharide-rich birch sap (PRBS), previously characterized as primarily low-molecular-weight polysaccharides (MW·1.29 kDa), in a rat model of kainic acid (KA)-induced acute seizures.MethodsRats received oral PRBS (6/10 mL/kg) for 7 days before KA-induced (15 mg/kg, i.p.) seizures. Seizure severity was evaluated using behavioral, electroencephalographic (EEG), and cerebral blood flow (CBF) monitoring. Brain tissues were analyzed via histology, Western blotting, and high-performance liquid chromatography (HPLC) for neuronal damage, neuroinflammation, blood-brain barrier (BBB) integrity, and glutamate metabolism.ResultsResults demonstrated that the higher dose (10 mL/kg) exerted potent anticonvulsant effects, significantly reducing tonic convulsion scores and EEG ictal spikes. Furthermore, the treatment mitigated KA-induced CBF deficits and prevented neuronal damage in the cortex and hippocampus. Mechanistically, PRBS suppressed glial activation, indicated by a decrease in GFAP+ and OX42+ cells and reduced expression of markers associated with a pro-inflammatory state (C3 and CD86). It also inhibited neuroinflammatory signaling by downregulating TLR4 and p-IkB levels while suppressing the overall activation of NF-kB p65, thereby decreasing the release of pro-inflammatory cytokines (IL-1b, IL-6, and TNF-a). Additionally, the treatment attenuated BBB disruption by reducing albumin extravasation and upregulating tight junction proteins (claudin-5 and occludin). Finally, it restored glutamate homeostasis by upregulating the astrocytic transporter GLT-1 and glutamine synthetase, while downregulating glutamine transporters (SNAT1/3), glutaminase, and the vesicular glutamate transporter VGLUT1.ConclusionPRBS exhibits potent antiseizure and neuroprotective properties that are closely associated with the modulation of TLR4/NF-kB-mediated inflammation, the preservation of BBB integrity, and the regulation of glutamate homeostasis, highlighting its potential as a natural therapeutic agent for seizures.