A. Sharma, J.V. Lafuente, D.F. Muresanua, A. Nozari, R. Patnaik, Z.R. Tian, A. Ozkizilcik, H. Mössler, H.S. Sharma
Uppsala University, Uppsala,
Keywords: sleep deprivation, head injury, cerebrolysin, alpha melanocyte stimulating hormone, brain pathology
Summary:Sleep deprivation (SD) is common in military personnel engaged in combat operations. Our previous reports show that 12 h SD alone induces brain pathology and continued until 72 h in a progressive manner. However, these military personnel with SD are also prone to traumatic brain injury (TBI). Thus, a possibility exists that TBI could further exacerbate SD induced brain pathology. Several lines of evidences suggest that both in TBI and in SD a decrease in alpha-melanocyte stimulating hormone (MSH) and brain derived neurotrophic factor (BDNF) levels occur in plasma as well as in the brain. This could be one of the leading causes of brain pathology in SD or in TBI. Thus, exogenous supplement of alpha-MSH and/or BDNF could induce neuroprotection in SD or TBI. In present investigation effect of concussive head injury (CHI) in SD induced brain pathology and effects of alpha-MSH and neurotrophic factors treatment leading to neuroprotection in a rat model was examined. SD was induced in rats using the inverted flowerpot methods surrounded by water level 1 cm below the platform (6.5 cm in diameter) that allow free movement but continuously sleep leads to fell down in water disturbing the sleep process. SD was induced in healthy rats as well as in rats that were subjected to CHI by dropping a weight of 114.6 g over the skull causing an impact of 0.224 N on the brain without skull fracture. Rats subjected to 48 h SD in CHI (24 h after insult) exhibited greater brain pathology e.g., higher leakage of Evans blue albumin and radioiodine (-I) by 3-to 4 fold as compared to naïve rats subjected to identical SD. Neuronal, glial and axonal damages using histopathological techniques were also exacerbated by several fold in CHI after SD. Plasma alpha-MSH and BDNF level shows significant reduction (alpha-MSH 8.34±0.23 vs. Control 20.34±0.12 pg/ml; BDNF 8.23±0.11 vs. control 22.34±0.21 pg/ml) in SD group after CHI as compared to SD group alone (alpha-MSH 15.13±0.12 pg/ml; BDNF 14.23±0.08 pg/ml). Intravenous administration of alpha-MSH (100 µg/kg) together with cerebrolysin (a balanced composition of several neurotrophic factors and active peptide fragments 5 ml/kg) significantly induced neuroprotection in CHI or SD groups alone. However, TiO2 nanowired delivery of alpha-MSH and cerebrolysin is needed to induce neuroprotection in SD rats after CHI. The levels of alpha-MSH and BDNF were also restored by this treatment in SD rats after CHI (alpha MSH 22.34±0.12 pg/ml; BDNF 23.34±0.17 pg/ml). Taken together our results are the first to point out that TiO2 nanowired administration of alpha-MSH and cerebrolysin induces superior neuroprotective effects following SD in CHI, not reported earlier.