Post-traumatic stress disorder (PTSD) is associated with persistent cognitive and emotional disturbances linked to hippocampal dysfunction, oxidative stress, and impaired neuroplasticity. Gallic acid, a naturally occurring polyphenol, possesses antioxidant and neuroprotective properties, but its effects in trauma-related disorders remain incompletely understood. Male Wistar rats were subjected to single prolonged stress (SPS) to induce PTSD-like phenotypes and, beginning 24 h after SPS, received gallic acid (10 or 100 mg/kg) or saline for 14 days. Anxiety-like behavior, fear extinction, and spatial learning and memory were assessed using the elevated plus maze, contextual fear conditioning with extinction, and Morris water maze, respectively. Hippocampal oxidative stress markers (MDA, SOD, and TAC), BDNF protein expression, and CA3 dendritic morphology were evaluated. SPS exposure induced anxiety-like behavior, impaired fear extinction, and deficits in spatial learning and memory, accompanied by increased lipid peroxidation, reduced antioxidant capacity, decreased hippocampal BDNF expression, and CA3 dendritic atrophy. Early post-stress gallic acid administration attenuated these behavioral alterations and was accompanied by improvements in hippocampal oxidative status, BDNF expression, and CA3 dendritic morphology, without detectable effects on locomotor activity or relative adrenal gland weight. Collectively, these findings indicate that early post-stress gallic acid administration attenuates SPS-associated behavioral and hippocampal abnormalities and that these effects are associated with antioxidant and neuroplasticity-related changes rather than establishing a causal mechanism. Further studies using delayed treatment paradigms and pathway-specific approaches are needed to determine the efficacy of gallic acid after establishment of the PTSD-like phenotype and to clarify the mechanisms underlying its effects.
Postictal hypoxia causes several consequences that are detrimental to the quality of life of people with epilepsy. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the primary phytocannabinoids from cannabis, have been shown to exhibit vasoactive and antioxidant properties that may mitigate the local oxygen deficiency observed after seizures. Here, we focus on the effects of CBD and THC on seizure-induced hypoxia. Adult Long-Evans rats of both sexes were assigned to drug-specific cohorts and the effects on local hippocampal oxygen were measured before and after seizure elicitation following either vaporized or oral administration of the two phytocannabinoids. Acute effects were assessed following a single administration of each drug, whereas chronic effects were evaluated over 28 days of daily treatment. In naïve rats, acute vaporized CBD significantly attenuated postictal hypoxia in both sexes, whereas acute oral THC attenuated postictal hypoxia in male rats. With chronic daily administration, phytocannabinoids produced time-dependent adaptations. Chronic vaporized CBD in females and chronic oral THC in males maintained attenuating effects on postictal hypoxia but exhibited partial tolerance, characterized by diminished effects on postictal oxygen decline in both sexes, recovery of postictal oxygen in females, and severity of hypoxia in males. These results demonstrate that acutely and chronically administered phytocannabinoids attenuate postictal hypoxia in a route-, sex-, and time-dependent manner. Together, these findings provide evidence that vaporized CBD and oral THC hold potential to treat the postictal hypoxia-induced comorbidities associated with seizures, potentially increasing the overall quality of life of people with epilepsy.
