NANODELIVERY OF DRUGS FOR NEUROPROTECTION IN SLEEP DEPRIVATION INDUCED BRAIN PATHOLOGY

Sleep deprivation (SD) is quite common in military personnel affecting their mental functions and decision-making capacity. Since SD is a severe stress, it would be possible that long-term SD could affect blood-brain barrier (BBB) function and brain pathology. Thus, it would be interesting to find out whether SD could induce brain pathology in model experiments. We examined SD induced BBB breakdown, brain edema formation and brain pathology in a rat model using an inverted flowerpot technique. Furthermore, potential therapeutic strategies in SD were also explored using nanodelivery of cerebrolysin. Our observations avowed that SD of 12 to 48 h causes BBB disruption, brain edema formation and neuronal damages in a progressive manner. We found significant increase in the BBB disruption, brain edema formation and neuronal injuries after 48 h SD. Measurement of brain derived neurotrophic factor (BDNF) showed 50 to 60 % decline in different brain areas in SD. Nanowired delivery of cerebrolysin 4 to 6 h after the onset of SD significantly reduced brain pathology and enhanced regional BDNF levels at 48 h SD. However, normal cerebrolysin given after the onset of SD has only minimal effects on regional BDNF level and brain pathology at 48 h. This indicates that nanodelivery of drugs have superior effects in achieving neuroprotection. This study will help create a database for suitable nanocarriers to use for drug delivery to the CNS as effective therapeutic tools in clinics for better therapeutic strategies in future.