Alpha-linolenic acid (LIN) has been shown to provide
neuroprotective effects against
cerebral ischemia. LIN is a potent activator of
TREK-1 channel and LIN-induced neuroprotection disappears in Trek1-/- mice, suggesting that this channel is directly related to the LIN-induced resistance of brain against
ischemia. However, the cellular mechanism underlying LIN induced
neuroprotective effects after
ischemia remains unclear. In this study, using a rat photochemical
brain ischemia model, we investigated the effects of LIN on the
protein abundance of astrocytic
glutamate transporter and AQP4, microglia activation, cell apoptosis and behavioral recovery following
ischemia. Administration of LIN rescued the
protein abundance of astrocytic
glutamate transporter GLT-1, decreased the
protein abundance of AQP4 and
brain edema, inhibited microglia activation, attenuated cell apoptosis and improved behavioral function recovery. Meanwhile,
TREK-1 was widely distributed in the cortex and hippocampus, primarily localized in astrocytes and neurons. LIN could potentiate the
TREK-1 mediated astrocytic passive conductance and hyperpolarize the membrane potential. Our results suggest that LIN provides multiple cellular
neuroprotective effects in
cerebral ischemia.
TREK-1 may serve as a promising multi-mechanism therapeutic target for the treatment of
stroke.