species in the particulate matter of cigarette smoke are long-lived (i.e., hours to months) compared to those in the gas phase [5], and can compromise organs other than the lungs [120,127]. In vivo chronic exposure of rat brain tissue to cigarette smoke significantly decreases membrane-bound ATPases, which alters ion homeostasis, and leads to increased Ca2+ and Na+ levels in the cytosol of various cell types [128], as well as increased Ca2+ in mitochondria [122], which is associated with neuronal injury or death [129]. Increased mitochondrial Ca2+ secondary to cigarette condensate exposure is associated with damage to the inner mitochondrial membrane (e.g., membrane swelling) and vacuolization of the matrix. Importantly, nicotine delivered independently of cigarette smoke does not appear to produce these adverse affects [122]. Nicotine administration in adolescent rats does, however, evoke cell injury and loss throughout the brain, with significant effects in the hippocampus of female rats but not males [130,131]. In general, the mechanisms underlying the observed nicotine-induced cell injury remain to be fully explicated.
