Research Paper TOTAL SLEEP DEPRIVATION COMPROMISES BLOOD–BRAIN BARRIER INTEGRITY AND IMPAIRS LEARNING AND MEMORY: A PROTECTIVE EFFECT OF GLIBENCLAMIDE AND RECOVERY SLEEP

The present study focused on investigating the possible neuroprotective potential of peripheral glibenclamide pretreatment and sleep recovery on sleep deprivation effects in rats and the possible mechanisms of action (s). Adult male rats were sleep deprived for a period of 3 days using grid suspended over water method. Morris water maze was used to reveal the effect of both sleep deprivation and the different treatments on learning and memory. Potential mechanisms were explored applying HPLCUV determination of hippocampal and cortical monoamines in rats. In addition, blood brain barrier intergrity was determined in different groups using Evans blue dye extravasation method. Sleep deprivation induced learning impairment and learning deterioration and neuromotor deficit. The concentrations of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) significantly decreased in both brain cortex and hippocampus after sleep deprivation Moreover, sleep deprivation increased blood brain barrier permeability and induced extravasation of the Evans Blue dye in the tested brain areas. Glibenclamide pretreatment antagonized sleep deprivation-induced learning impairment and learning deterioration, and neuromotor deficit. However, pre-treatments with glibenclamide significantly increased the concentrations of 5-HT and NE in rat cortex and hippocamps and minmized the blood brain barrier permeabilty. Moreover, recovery sleep for 48 hours remarkably antagonized sleep-adverse effects. These changes might suggest that the neurochemical changes and the impairment of blood brain barrier function areat least partly the underlying mechanism of adverse effects of sleep deprivation on memory and learning. In addition, the potective and restorative effects of glibenclamide and sleep recovery, respectively, against sleep deprivation might be mediated through rebalance the brain chemistry and restoring the normal function of blood brain barrier.