A: Zolpidem significantly improves TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor circuits. The study found that zolpidem:
Flattened rest and active input/output curves.
Reduced intracortical facilitation (ICF).
Was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum.
Correlations were found between changes in dystonia severity and changes in active input/output curves and brain metabolism.
Patients with lower resting motor threshold (RMT) and higher rest and active input/output curves exhibited a better response to zolpidem compared to placebo.

A: Zolpidem significantly reduces the frequency of KCl-induced CSDs without altering the wave dynamics or neurovascular coupling. This suggests that zolpidem can mitigate the propagation of CSDs, potentially reducing secondary neuronal injury and promoting functional recovery post-stroke.

A: Zolpidem does not significantly alter the protein levels of α1-GABA-A receptors or GABA transporters (GAT1-3) but significantly reduces NKCC1 mRNA expression in the frontal cortex on day 3 post-stroke. This suggests that zolpidem modulates post-stroke chloride homeostasis without directly affecting GABAergic protein levels, potentially contributing to its neuroprotective effects.

A: Zolpidem administration significantly reduces elevated glutamate levels in the striatum, with the most pronounced effect observed at 24 hours post-stroke. This reduction persists until day 3 post-stroke, suggesting that zolpidem helps restore neurochemical balance and provides neuroprotection by counteracting glutamate-induced neuronal damage.

A: Zolpidem significantly reduces infarct volume, lowers glutamate levels, and improves motor recovery when administered early (within 1.5 hours) post-reperfusion. It enhances phasic GABAergic signaling via α1-GABA-A receptors, reduces NKCC1 mRNA expression, and suppresses the frequency of cortical spreading depolarizations (CSDs), which are key propagators of secondary neuronal injury. These findings suggest that zolpidem is a promising candidate for drug repurposing in stroke treatment, targeting both early neuroprotection and longer-term functional recovery.