Browsing by Author "Mensah-Kane, Paapa"
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Item Hyperbaric Oxygen as Potential Treatment for Chemotherapy-Related Cognitive Impairments(2024-03-21) Trinh, Oanh; Mensah-Kane, Paapa; Shi, Helen; Sumien, NathaliePurpose: “Chemobrain”, characterized by impaired attention, learning and memory retention, is a prevalent condition affecting approximately 75% of patients undergoing cancer treatments. Chemotherapy-related cognitive impairment (CRCI), a subtype of “chemobrain”, can persist for up to 20 years post-treatment, significantly diminishing the daily quality of life for survivors and caretakers. Very few interventions are available to alleviate the effects of chemotherapy on the brain. One potential treatment is hyperbaric oxygen therapy (HBOT), which has shown neuroprotective effects in conditions such as Alzheimer’s disease, traumatic brain injury, and stroke. The current study investigated the effects of HBOT on cognitive impairments induced by commonly used chemotherapeutic agents, and studied the underlying mechanisms with a focus on cellular senescence. Methods: Four-month-old male and female C57BL/6 mice were injected (i.p.) with saline or chemotherapeutic cocktails (Methotrexate (37.5 mg/kg) + 5-Fluorouracil (50 mg/kg)) once a week for three weeks. Simultaneously, half of the mice underwent daily HBOT session (2.4 ATM for 90 min). Morris water maze was used to measure spatial learning and memory. Hippocampus was evaluated for markers of cellular senescence using western blot analyses. Results: Chemotherapy exposure impaired spatial learning and memory, which was attenuated by HBOT in male mice only. The exposure was also associated with increased levels of p16INK4a, ɣH2AX, and b-galactosidase (cellular senescence markers), and increased levels of cleaved-Lamin B1 (a surrogate marker of caspase-6 activity relating to apoptosis) in male hippocampus. HBOT seemed to reduce the effects of chemotherapy on ɣH2AX, b-galactosidase, and cleaved-Lamin B1, but not on p16INK4a in males. Conclusion: HBOT reduced cognitive impairments associated with chemotherapy exposure. Interestingly, females were not impaired by the chosen chemotherapeutic cocktail. Cellular senescence and apoptosis may play a role in the beneficial effects of HBOT.Item Hyperbaric Oxygen Therapy: a potential Alzheimer's disease modifier?(2021) Sumien, Nathalie; Mensah-Kane, Paapa; Dory, Lad; Vann, PhilipPurpose: Current treatment of Alzheimer's disease (AD) is symptomatic, involving anti-cholinesterase and an NMDA antagonist. Over time, this increase in AD incidence, will bring dire consequences not just on the quality of life but also as an economical burden, as Medicare spending for AD is projected to increase to 1 trillion by the year 2050. Based on these numbers, it necessary to identify a solution. It is therefore, not surprising that the Alzheimer's Project Act was passed about 9 years ago to support this course. Though a complex disease, oxidative stress and neuroinflammation are key factors in the pathogenesis. Procedures or treatments that tend to reduce these two factors could probably reverse/modify the progression of the disease. Hyperbaric Oxygen Therapy (HBOT) seems promising for neurological conditions. Therefore, we aim to explore whether HBOT can improve cognition Methods: Young and adult mice were each divided into 4 groups consisting of control-HBOT, control+HBOT, 5xFAD-HBOT and 5xFAD+HBOT. HBOT was started at either 4 or 9 months and continued until the mice were euthanized. Two behavioral tests to study cognition were used. Results: HBOT reversed the deficits in the 5xFAD in the adult mice but not in the young ones. Conclusion: This work though preliminary does support HBOT as a viable option. More work is needed to determine the optimal timing and frequency of the treatment, as well as the mechanism of action underlying its benefits.Item Hyperbaric Oxygen Treatment improved Cognitive deficits in a mouse model of Alzheimer's Disease(2022) Mensah-Kane, Paapa; Vann, Philip; Davis, Delaney; Dory, Lad; Sumien, NathaliePurpose: Alzheimer's disease (AD) is an economic burden affecting 40 million people worldwide and projected to increase to 120 million by the year 2050. Current approved treatments of AD only manage symptoms, involving anti-cholinesterase or NMDA antagonist. Seeking out new therapeutics and interventions that can reverse and alleviate the devastating effects of this disease has become paramount. Though a complex disease, there are major factors such as hypoxia, oxidative stress, and neuroinflammation that have been heavily involved in the pathogenesis of AD. Interventions that can reduce these two factors would likely reverse the progression of the disease. Hyperbaric Oxygen Therapy (HBOT), which has been used for the past 50 years for thermal burns, decompression sickness among other conditions, seems promising for neurological conditions such as traumatic brain injury and stroke. It has been shown to reduce inflammation and hypoxia. At the center of AD controversy also, is the relative vulnerability of the different sexes to AD. Whereas most studies in the US show no difference in incidence, studies in Europe have demonstrated a higher risk in women than men. On the contrary another study in United Kingdom reported men are at a higher risk. Thus, it has become more important to use both sexes in any study that seeks a successful treatment. Therefore, our aim was to explore whether HBOT can improve cognition in both male and female 5xFAD (AD model) mice. Methods: A total of 132 male and female 5xFAD and wildtype (WT) mice were randomly assigned to one of four experimental groups consisting of WT-HBOT, WT+HBOT, 5xFAD-HBOT and 5xFAD+HBOT. HBOT (O2 pressure at 2.4 ATA maintained for 90 min) daily (5 days/week) was started at 9-10 months and continued until the mice were euthanized at 12-13 months. Morris water maze test for spatial learning and memory, active avoidance T maze test for cognitive flexibility and fear conditioning test for associative learning were carried out at 1 month into the treatment with HBOT. Results: HBOT improved spatial learning and memory deficits in 5xFAD males but not in females. However, cognitive flexibility impairments were reversed with HBOT in 5xFAD females but not males. Also, HBOT improved associative learning in 5xFAD females, a deficit which was absent in males. Conclusion: This work does support HBOT as a viable option for reversing cognitive impairment associated with an AD phenotype with some sex differences depending on cognitive domain. Future work will seek to evaluate the mechanisms of action of HBOT including the possible involvement of epigenetics and sex differences, to help bring some clarity to the equivocal vulnerability of males and females to AD.