Trans-cinnamaldehyde attenuates neuronal cytotoxicity and memory impairment in comorbid exposure to sleep-deprivation and formalin inhalation in rat model

Synapse impairment is associated with decline in learning ability and memory loss, which can be activated by enhanced oxidative stress, inflammation and hypermyelination of neurons in the prefrontal cortex (PFC), hippocampus (Hipp), and other brain regions. Thus, we examined trans-cinnamaldehyde (TCA) neuroprotective mechanisms in cortico-hippocampal axis of rat deprived of sleep with concomitant long-time exposure to formalin inhalation. Thirty-six (36) healthy male Wistar rats (average of 170 ± 10 g) were randomly assigned into six experimental groups (n = 6). Positive control group (CON), TCA (40 mg/kg bw) control group (TCA), sleep deprivation exposure group (SD), 20% formalin inhalation group (FEx), SD + FEx group (SD + FEx) and SD + FEx + TCA group (SD + FEx + TCA). 20% formalin exposure was done via inhalation, with sleep deprivation for 8 h a day, 5 days/week, from day 1 to 56 while TCA was given intraperitoneally, from day 28 to 56 and thereafter, behavioral, biochemical, immunohistochemistry and histomorphology was assessed. SD, FEx and SD + FEx exposure provokes loss of body weight across days, impair short- and long-term memory functions and heightened pro-oxidants molecules with marked decreased endogenous antioxidants status in cortico-hippocampal brain region of the animal. The degree of cortico-hippocampal proinflammatory mediators were further upregulated supported with loss of pyramidal neurons, severe white matter degeneration, axonal loss and hypermyelination. In addition, SD + FEx exposure exacerbates cortico-hippocampal Nrf2 immunopositive cells. Herein, all these assaults were mitigated by TCA treatment, due to its ability to modulate Nrf2 protein, oxido-inflammatory signaling molecule and restore cortico-hippocampal neurons. Taken together, our findings showed the positive neuroprotective effects of TCA against neurodegeneration associated with SD + FEx exposure, by reducing oxido-inflammatory molecules, increasing the endogenous antioxidant defense system modulating Nrf2 protein and abating the loss of cortico-hippocampal neurons and histoarchitecture.