Abstract â–¡ 77

Maternal cigarette smoking during gestation is associated with an increased risk of Sudden Infant Death Syndrome. This may be due to abnormal development of the brainstem centres that control respiration. These areas of the brainstem rely heavily on the neurotransmitters glutamate and GABA for regulation of respiratory patterns. To examine the effects of gestational smoking on the development of brainstem respiratory centres, an animal model was employed. Pregnant Wistar rats were exposed to the equivalent of either 7 or 15 standard cigarettes per day throughout the entire gestational and lacational periods. Two groups of controls were used: 'sham' controls were placed in the smoke exposure apparatus in the absence of cigarette smoke for the same period of time as smoke exposed rats, and room controls. At postnatal day 7 (P7), P10, P14 and P21 a number of rat pups were euthenased via intraperitoneal injection of sodium pentobarbital and perfused with paraformaldehyde. Blood carbon monoxide and nicotine/cotinine levels were also measured. Brainstem and attached cerebella were obtained for immunohistochemical and cytoarchitectural analysis. The distribution of the GABA transporter, GAT-1 and the glutamate transporters GLAST and GLT-1 were examined using immunohistochemical methods. Significant differences were found in the number of GLAST-expressing elements in respiratory-related areas of the brainstem of smoke-exposed rat pups when compared to sham controls and room controls. These areas included the locus coeruleus, where significant gliosis was apparent in smoke exposed rats. A possible physiological outcome of this abnormality is an increase in the uptake of glutamate into glial cells which dampens glutamatergic excitatory inputs to the locus coeruleus, reducing arousal responses during sleep as a result of hypoxia or hypercapnea. Significant cytoarchitectural differences were present in the cerebella of the smoke-exposed rat pups at all ages. The external granular layer was thicker than controls, and Purkinje cell bodies were rounded and small when compared with controls. These changes are indicative of delayed cerebellar maturation. These presence of brainstem and cerebellar abnormalities in the offspring of smoking female rats may be a result of in-utero hypoxia which results from decreased maternal blood-oxygen carrying ability caused by cigarette smoke.