Silica and Carbon Nanoparticles Exacerbate Pathophysiology of Concussive Brain Injury

Concussive brain injury (CBI), i.e., shaking of brain inside the cranial compartment without any apparent sign of visible head injury is quite common in military personals engaged in combat operation across the World. Roadside blast or missile explosion often leads to CBI causing mild to moderate brain dysfunction and alterations in cognitive and sensory motor functions. If untreated the consequences of the CBI could be grave leading to personality disorder, depression and other psychiatric or physical illnesses. However, this is still unclear whether these CBI symptoms could be further altered by acute or chronic exposure to various nanoparticles present in the environment or due to gunpowder explosion. Since our military personals are often exposed to silica (SiO2) nanoparticles from the desert environment and carbon nanopartiocles from the explosion site it is likely that the consequences of the CBI under such conditions could be different from that occurring in home or other clean environments. The CBI was produced in Equithesin anesthetized (3 ml/kg, i.p.) rats by inflicting a blunt head injury on right parietal skull bone using a 114.6 g of cylindrical iron rod tapering towards one end (2 mm²) not pointed enough to pierce the skull from a height of 20 cm. This weight and distance will result in an impact injury of 0.224 N on the right parietal skull surface without breaking it. In a separate group of rats SiO2 (50 to 60 nm) or carbon nanoparticles (45 to 50 nm) were administered daily in a suspension of Tween 80 in a dose of 50 mg/kg (i.p.) for 7 days. In these nanoparticles treated animals CBI was inflicted on the 8^th day. Uninjured animals were used as controls. After 5h, 8 h or 24 h of CBI in normal or nanoparticles treated animals, breakdown fo the blood-brain barrier (BBB) function to Evans blue albumin and ^[131]Iodine in relation to brain edema development using changes in water content were evaluated. CBI in normal animals resulted in marked increase in BBB disruption and brain edema formation that was most marked in the contralateral left half (Evans blue +68%, radioiodine +98%; water content +1.25 %) of the brain as compared to the ipsilateral right injured side. The left hemisphere was visually more swollen than the right side confirming the CBI that often reflects on the contralateral side of the brain. These changes were further exacerbated in nanoparticles treated animals. Interestingly SiO2 treatment showed much more aggravation of BBB leakage (+220 %) and brain edema (+3.2 %) than Carbon nanoparticles (BBB +125%; brain water 2.1% respectively) intoxication. However, in both cases the left hemisphere was much more adversely affected than the right injured hemisphere. These changes were more prominent after 8 h CBI than 5 h and further increased by 50 to 80 % over at 24 h after CBI. Taken together our observations are the first to show that nanoparticles intoxication results in exacerbation of CBI induced brain pathology, not reported earlier.