Hyperbaric oxygen-induced seizures cause a transient decrement in cognitive function.

Hyperbaric oxygen-induced seizures are classified as brief, generalized tonic-clonic seizures. They are believed to cause no residual cognitive damage, although this has not been investigated in depth. In the present study, we examined whether hyperbaric oxygen-induced seizures cause impairment of behavioral and cognitive abilities. Cognitive status was assessed using four behavioral tests: Y-maze, novel object recognition, the elevated plus maze, and a passive avoidance task. Three time intervals were examined: 24h, and 7 and 30 days after the seizures. We found transient impairment of performance in the compressed group on three tests (the novel object recognition paradigm, the Y-maze paradigm, and the passive avoidance task). On the elevated plus maze test, the impairment persisted. The time interval to the appearance of deficits and to eventual recovery was not the same for the different tests. We conclude that hyperbaric oxygen-induced seizures result in transient impairment of performance on behavioral tests in a mouse model. Further investigation is required to establish the mechanism and location of injury, and to determine whether the performance decrement on the elevated plus maze test represents permanent damage or transient damage with slow resolution. These new findings should be taken into account when planning hyperbaric oxygen treatments, to ensure that the chosen protocol is therapeutic yet minimizes the risk of CNS oxygen toxicity.

The nuclear factor erythroid 2-like 2 activator, tert-butylhydroquinone, improves cognitive performance in mice after mild traumatic brain injury.

Traumatic Brain injury affects at least 1.7 million people in the United States alone each year. The majority of injuries are categorized as mild but these still produce lasting symptoms that plague the patient and the medical field. Currently treatments are aimed at reducing a patient's symptoms, but there is no effective method to combat the source of the problem, neuronal loss. We tested a mild, closed head traumatic brain injury model for the effects of modulation of the antioxidant transcription factor Nrf2 by the chemical activator, tert-butylhydroquinone (tBHQ). We found that post-injury visual memory was improved by a 7 day course of treatment and that the level of activated caspase-3 in the hippocampus was reduced. The injury-induced memory loss was also reversed by a single injection at 30 min after injury. Since the protective stress response molecule, HSP70, can be upregulated by Nrf2, we examined protein levels in the hippocampus, and found that HSP70 was elevated by the injury and then further increased by the treatment. To test the possible role of HSP70, model neurons in culture exposed to a mild injury and treated with the Nrf2 activator displayed improved survival that was blocked by the HSP70 inhibitor, VER155008. Following mild traumatic brain injury, there may be a partial protective response and patients could benefit from directed enhancement of regulatory pathways such as Nrf2 for neuroprotection.