Hari S Sharma
Uppsala University, Sweden
Hari S Sharma is the Director of Int. Experimental CNS Injury Research & Repair, University Hospital, Uppsala University, Sweden. He is actively engaged on research in brain injuries, blood-brain barrier and brain edema since last 30 years. He received the 1st US Neurosurgeon Anthony Marmarou Brain Edema award by the International Brain Edema Society, Tokyo, Japan in October 2011 and Top Innovation Award on “Nanowired cerebrolysin for neuropathic Pain” at National Innovation & Showcase Summit Washington DC, USA May 12-16, 2013. He published over 350 research papers in reputed Neuroscience journals.
Accumulation of ubiquitin within the brain after trauma leads to neurodegenerative changes or brain pathology. Our previous reports show that acute heat exposure leads to breakdown of the blood-brain barrier (BBB) resulting in edema formation and cellular injury. Thus, military personnel engaged in combatoperations in summer heat and prone to silica dust (SiO2 nanoparticles) exposure may result in exacerbation of their brain dysfunction. Since ubiquitin expression is increased following CNS injurywe examined ubiquitin expression in brain following SiO2 exposurein heat stress in rats. Furthermore, neuroprotective efficacy of cerebrolysin, a multimodal drug with pleotropic activity due to several neurotrophic factors and active peptide fragment on ubiquitin expression was also evaluated in these conditions. Our observations show that rats subjected to 4 h heat stress in a Biological Oxygen Demand incubator (BOD) resulted in over expression of ubiquitin in several brain areas (+40 to 120 %) from control group. Chronic SiO2 intoxication (50-60 nm, 50 mg/kg, i.p. daily for 7 days) resulted in exacerbation of ubiquitin accumulation by further 150 to 260% in the identical brain areas following heat exposure. Cerebrolysin in low doses reduced the ubiquitin expression in heat stress but required high doses or TiO2 nanowired delivery to have similar effectsin SiO2 intoxicated group. These observations are the first to suggest that (i) ubiquitin expression in the brain following heat stress is involved in neuronal damages, (ii) that is further exacerbated by SiO2 intoxication, (iii) and cerebrolysin downregulates ubiquitin expression to induce neuroprotection, not reported earlier.