The neuroprotective roles of ALA have been reported in several stroke studies [27,31-36]. Recently, several molecular and clinical studies emphasized on the therapeutic potential of Omega-3 polyunsaturated fatty acids for treating a number of neurological and psychiatric diseases. Nevertheless, the mechanisms underlying these effects are still poorly understood.

In 2009, Blondeau et al. showed that subchronic ALA injections in mice induced neurogenesis in the hippocampus, increased in vivo and in vitro BDNF expression, promoted Neural Stem cell (NSCs) proliferation and synaptogenesis, enhanced synaptic vesicle fusion and protein levels, and induced antidepressant-like behavior. Furthermore, they observed that pre- and post-treatments with repeated ALA injections decreased the infarc volumes and mortality caused by middle cerebral artery occlusion (MCAO) [37]. Nguemeni et al. in 2010 reported that dietary supplements of ALA in an enriched rapeseed oil diet could significantly reduce the MCAO-induced mortality rate and infarct volumes in mice [38]. In light of these studies on ALA, we examined the effect of dietary consumption of ALA on the blood levels of BDNF and MDA. To the best of our knowledge, this is the first study on healthy adult humans that measured both BDNF and MDA levels, used oral consumption of ALA, and determined sex differences in response to ALA intake. The results demonstrated that the levels of BDNF and MDA both increased in individuals who took ALA.

Neurotrophins are small proteins that are crucial for neuronal differentiation, growth, survival, and plasticity [39]. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) are members of the mammalian neurotrophin family. The impact of these molecules on the nervous system is mediated by the tropomyosin receptor kinase (Trk) receptors and membrane-bound receptor tyrosine kinases that activate a number of cell signaling pathways which are linked to growth, differentiation, and survival [40]. The importance of neurotrophin signaling in brain development is well elucidated with findings that showed that knockout mice for any of the neurotrophins or their receptors were fatal or exhibited severe neural defects [41]. Neurotrophin signallings have important roles in the survival and integration of new neurons. For instance, BDNF triggers the TrkB receptor tyrosine kinases. BDNF also increases the number and survival of NSCs in the subventricular zone (SVZ) and olfactory bulbs [42,43]. Likewise, knocking down the TrkB receptors or disrupting the BDNF signaling pathway in dentate gyrus progenitors can lead to the formation of shorter dendrites, reduced spine, and eventually death [44].

BDNF signaling promotes the survival of newly-generated neurons. In addition, defects in this pathway are associated with decreased neuronal survival and neurogenesis as well as the incidence and progression of several neurological disorders, such as schizophrenia, bipolar disorder, Alzheimer’s disease, and age-related cognitive decline [43,45,46]. Furthermore, BDNF indirectly increases the transcription of Bcl-w gene, an anti-apoptotic member of the Bcl-2 family [47]. Thus, BDNF decreases neuronal apoptosis. In addition, BDNF increases adhesion, migration, and survival of neurons. This neurotrophic molecule also enhances neurogenesis, synaptic plasticity, and neuronal differentiation through the BDNF/TrkB-TK+ signaling pathway, an important pathway for neuronal viability and function [48-57].

ALA treatment can be beneficial for the treatment of many neurological diseases, particularly stroke, which is the third leading cause of death worldwide [58,59]. Our findings were in accordance with the previous studies, confirming that ALA increases the expression of BDNF. Considering the neuroprotective and neurotrophic characteristics of BDNF, ALA treatment could be a feasible approach to reduce infarct size in stroke patients. Thus, ALA could be used in adjunction with routine stroke treatments to minimize lesions caused by stroke. Further research could attempt to replicate the present findings with a larger sample size. Furthermore, studying the molecular mechanisms underlying the positive effects of ALA on the nervous system might also be helpful. Future research can investigate the effects of ALA intake on stroke patients.