Cold Environment Exacerbates Nicotine Induced Brain Pathology

Recent studies show that prenatal exposure of nicotine in small amounts leads to neuronal damages in several brain areas. However, exposure of nicotine to young adults causing brain dysfunction is still not well known. In this investigation we examined a low dose of nicotine in young adult rats on brain dysfunction e.g., breakdown of the blood-brain barrier (BBB) permeability, brain edema formation and neuronal injuries. Since environmental factors i.e., heat or cold could also influence nicotine neurotoxicity, we examined effects of cold exposure on nicotine neurotoxicity using standard procedures. Young adults male Wistar rats (20 to 25 weeks of age) were exposed to Nicotine hydrochloride (9 mg/kg, s.c.) once daily for 1 week either at room temperature (21±1°C) or at cold environment (+8±1°C). On the 8^thday, BBB permeability to Evans blue albumin and brain water content was examined. The neuronal damages were evaluated using Nissl or Haematoxylin & Eosin methods using standard histopathological procedures. Rats subjected to nicotine exposure at room temperature showed 64 % increase in Evans blue albumin extravasation as compared to saline treated rats under identical conditions. These nicotine treated rats also exhibited increase in brain water content by 0.6 to 0.9 % from the saline group. A significant increase in number of neuronal distortion and damages were seen in in the brain stem, cerebral cortex and cerebellum following nicotine exposure in rats as compared to saline treated group at room temperature. Interestingly, nicotine exospore in rats at cold environment further exacerbated the brain pathology in wide areas of the brain. Thus, the neuronal damages were intensively seen in hippocampus, striatum and thalamus apart from brain stem, cerebral cortex and cerebellum. The breakdown of the BBB to Evans blue was further increased by 80 to 120 % from the identically exposed animals to nicotine at room temperature. The brain edema formation as measured using brain water content was enhanced by 1.5 to 2 % in cod environment following nicotine exposure as compared those treated at room temperature. Taken together these results demonstrate that small doses of nicotine is able to induce profound neurotoxicity in young adult rats and this neurotoxicity is further exacerbated when identical nicotine exposure is made under cold environments. Further studies are in progress to find out the role of oxidative stress in causing nicotine induced neurotoxicity.