Ayahuasca reverses ischemic stroke-induced neuroinflammation and oxidative stress.

BACKGROUND

Ischemic stroke is a leading cause of death and disability worldwide. Survivors face disability and psychiatric sequelae resulting from ischemia-induced cell death and associated neuroinflammation, and oxidative stress. Herbal medicines have been shown to elicit neuroprotective effects following stroke due to their anti-inflammatory and antioxidant effects. Preliminary evidence suggests that Ayahuasca (AYA), a decoction made from the vine Banisteriopsis caapi containing β-carbolines and the shrub Psychotria viridis containing N, N-Dimethyltryptamine, might attenuate ischemia-induced neuroinflammation and oxidative stress. Therefore, in this study we investigated the putative protective effects of AYA in the middle cerebral artery occlusion (MCAO) model of ischemic stroke.

METHODS

Wistar rats were subjected to the MCAO stroke model or sham surgery on day 0. After 24-h, rats were treated for three days with AYA (2 and 4 mL/kg, gavage) or saline. Neurological score was assessed for 72-h post-stroke. Rats were tested in the elevated plus maze, open field, and novel object recognition tests to assess locomotion, anxiety-like behavior, and recognition memory. Interleukin (IL)-6, IL-10 myeloperoxidase (MPO) activity, and the nitrite/nitrate (N/N) concentrations were determined in the prefrontal cortex (PFC), hippocampus (HPC), hypothalamus (HYP) and cortex. as markers of inflammation. Oxidative stress was quantified in the same brain areas as measured by the levels of thiobarbituric acid reactive species (TBARS), protein carbonylation, and superoxide dismutase (SOD), and catalase (CAT) activity. Mitochondrial metabolism was assessed quantifying the activity of complex 1(CI), CII, citrate synthase (CS), succinate dehydrogenase (SDH), and creatine kinase (CK).

RESULTS

No differences were observed regarding neurological deficits, locomotion, anxiety-like behavior, and recognition memory. However, AYA reversed the stroke-induced increase in IL-6 levels in the PFC and the HPC, IL-10 in the PFC, HPC, and HYP, MPO activity in the PFC, and N/N concentration and CAT activity in the HYP. Moreover, AYA decreased TBARS levels in the PFC and HPC and brain-derived neurotrophic factor (BDNF) in the PFC, and increased SOD activity in the cortex. Lastly, AYA increased CI activity in the HPC and cortex and decreased SDH and CK activity in the HPC.

CONCLUSION

AYA administration following ischemic stroke modulates oxidative stress and neuroinflammation in the PFC, HPC, and HYP. Despite no significant improvements in neurological or behavioral scores, these molecular changes suggest a neuroprotective role of AYA. Future studies should explore the timing of AYA treatment and putative long-term effects on functional recovery, as well as its potential in other brain regions critical for cognitive and motor functions.