Treatment of hyperbaric oxygen combine with cannabidiol promote recovery of brain damage in newborn rats with hypoxia-ischemia

Abstract

Objective: Hypoxic-ischemic (HI) encephalopathy is a severe disease seen commonly in clinical settings. However, there is a limited body of work on effective therapies to repair HI brain damage. To test the potential neuroprotective effects of cannabidiol (CBD) and hyperbaric oxygen (HBO) treatments against HI brain damage, we carried out series of experiments on newborn rats with brain damage induced by HI. Methods: We included 7-day-old newborn rats in this study. After creating the HI model, rats were grouped into an untreated HI model group, an HI+HBO-treated group, an HI+CBD-treated group, HI+HBO+CBD-treated group, and a sham control group. After one week of treatment, a subset of pups completed a T-maze task, and we collected CSF to measure the concentration of NSE and S100 β protein. Afterwards, the pups were sacrificed and we measured the concentration of MDA, SOD, TNF-a and IL-β and expression level of TNF-a and NSE in hippocampal tissue. The remaining pups completed the radial arm maze and foot fault test. Results: Two weeks after HI (P22), pups showed reduced correct responses to retraction in the T-maze test, and P30 pups with HI needed more time to visit 3 baited arms. The number of errors increased in the radial arm maze, and number of foot-faults also increased in the foot-fault test. Along with loss of brain weight, concentration of SOD was reduced and MDA, TNF-a, and IL-β were increased in brain tissue. NSE and S100 β protein concentration increased in CSF, as well as the expression level of TNF-a and NSE. Pups that were treated with HBO, CBD, or HBO+CBD showed less brain weight loss and better performance on behavioral tests. They also had increased SOD and reduced MDA, TNF-a, and IL-β level of brain tissue, as well reduced NSE and S100 β protein in CSF. The expression level of TNF-a and NSE were also reduced. HBO+CBD treatment exhibited better therapeutic effect than HBO or CBD alone. Conclusions: The combination treatment of HBO+CBD on rat pups with HI-induced brain damage achieved better results in reducing brain damage and preserving neurobehavioral performance than HBO or CBD alone. This novel therapeutic may be an appropriate avenue for exploration in other models, given its neuroprotective potential. Keywords: hypoxia-ischemia; cannabidiol; hyperbaric oxygen; brain damage; combination treatment; neuroprotective