Hyperacute intervention with DGMI for optimized stroke recovery: Modulating immune and inflammatory pathways in motor...

Long-term neurological dysfunction following stroke significantly impairs patients' quality of life. Ginkgo biloba L (GBL), a traditional Chinese herbal medicine, has shown promise in treating ischemic stroke and related disorders. Diterpene Ginkgolides Meglumine Injection (DGMI), derived from GBL, has demonstrated improved recovery outcomes in stroke patients when administered during the hyperacute phase (HAP) in clinical studies, yet the underlying mechanisms remain elusive.

Utilizing a Transient Middle Cerebral Artery Occlusion (tMCAO) model, we evaluated the effects of DGMI at varying doses and administration times on neurological function, brain injury, and identified key genes/pathways via RNA-seq and bioinformatics analyses, validated by RT-PCR. An in vitro LPS-induced astrocyte activation model was used to evaluate DGMI's anti-inflammatory effects.

DGMI administered during the hyperacute phase (HAP, 0.5 h post-tMCAO) exhibited superior neuroprotection compared to the acute phase (AP, 24 h post-tMCAO) in mice. HAP-DGMI significantly enhanced survival rates, reduced neurological deficit scores, infarct sizes, and neuronal apoptosis, with more pronounced improvements observed on days 3 and 7 post-tMCAO. Transcriptome sequencing revealed that HAP-DGMI more effectively normalized abnormal gene expression profiles, particularly in genes involved in immune and inflammatory pathways, in both motor (M1) and sensory (S1) cortices. Additionally, HAP-DGMI reversed a higher proportion of disease-characteristic pathways compared to AP.

These findings underscore the potential of early HAP intervention with DGMI in enhancing neuroprotection and functional recovery in AIS bymodulating key immune and inflammatory genes and pathways, providing experimental and theoretical support for the clinical application of DGMI.