Garlic-Derived S-allylcysteine Improves Functional Recovery and Neurotrophin Signaling After Brain Ischemia in Female Rats.

Background/

Objectives

Ischemic stroke is a leading cause of death and disability, and neuroprotection therapies, or those that increase recovery, are not available. While the garlic-derived bioactive compound S-allyl cysteine (SAC) has shown neuroprotective properties, its subacute long-term effects remain underexplored, particularly in females.

Methods

We evaluated whether SAC supports functional recovery after ischemia/reperfusion (IR), focusing on neurotrophin signaling, tropomyosin receptor kinase B (TrkB), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK). Adult female Wistar rats underwent 1 h of ischemia and 15 days of reperfusion. SAC (100 mg/kg, i.p.) was administered at the onset of reperfusion and daily for 15 days. Motor and cognitive deficit tests were performed. Infarct area, Ki67, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), pTrkB, pAKT, and pERK levels were quantified in the cortex, striatum, and hippocampus.

Results

MicroPET analysis revealed comparable glucose uptake between the IR and IR + SAC groups, indicating similar ischemic severity. SAC reduced infarct area (54.7%) and significantly improved motor deficits (53.9%), circling behavior (38.9%), and long-term memory compared with ischemia/reperfusion (IR) animals. SAC increased the proportion of Ki67-positive cells (4.3-fold in the cortex and 1.8-fold in the striatum) and enhanced neurotrophin levels, NGF (cortex), BDNF (cortex and striatum), VEGF (striatum), pTrkB, pAKT, and pERK (cortex and striatum).

Conclusions

SAC supports post-ischemic recovery, improving motor performance and preserving long-term recognition memory, effects that could be associated with increased cell proliferation, neurotrophin levels, and activation of the TrkB, AKT, and ERK pathways.