Abnormal neural behaviors of neonatal rat due to hyperthermia and low dosage of cigarette exposure during pregnancy / 中国组织工程研究

ABSTRACT

BACKGROUND: Neural behavior is a sensitive parameter for predicting abnormal central nervous growth that is resulted from multiple factors. Therefore this study was designed to explore the influence of hypothermia and cigarette smoke exposure during pregnancy on neural behavioral growth of neonatal rats.OBJECTIVE: To study the influence of hypothermia and cigarette smoke exposure on neural behavioral growth of neonatal rats.DESIGN: Randomized case control study based on experimental animals. SETTING: Obstetric and Gynecological Department , Third Affiliated Hospital of Xinxiang Medical College; Cytobiological Department of Xinxiang Medical College.MATERIALS: Totally 270 healthy unpregnant SD rats were obtained, including 180 males with body mass of 190- 210 g, and 90 female rats with body mass of 225-275 g. Rats were raised with granulated feed and drinking water routinely in room of 25 ℃ with natural sunlight. Male and female rats in estrus were put in the same cage overnight in proportion of 2: 1, pregnancy was confirmed if vaginal bolt was observed the following morning. Totally 160 pregnant rats were obtained and randomly divided into 16 groups that were exposed to hyperthermia, cigarette smoke or their combination and by this way, earlier reflex, learning and memory of neonatal rats were observed after natural delivery,INTERVENTIONS: From the second day of pregnancy, rats in 37 ℃, 41 ℃,42 ℃ hyperthermia combining cigarette group received subcutaneous injection of 1 mL smoke hydrotrope every other day, while rats in 25 ℃ control group and 37 ℃, 41 ℃, 42 ℃ single hyperthemia groupwere given 2.0 mL double distilled water every day for totally 7 times. From the pregnancy of 10 days, pregnant rats were put into incubator, and rats anus temperature should be kept respectively at(37 ±0.5) ℃, (41 ±0.5)℃, (42 ±0.5)℃in the 37 ℃, 41 ℃, 42 ℃ of single hyperthemia groups and the temperature should last for 2.0 minutes; nats of 37 ℃, 41 ℃, 42 ℃hyperthemia combining cigarette group received the same treatment and were divided into four subgroups with the duration of 0. 5, 1.0, 1.5, 2.0 minutes respectively;rats in 25℃ control group were not exposed to hyperthermia. Rats were then singly raised from the pregnancy of 18 days for natural delivery. Pregnant days, number of neonatal rat and death rats were recorded, and visible malformation was observed. The average body masses of each cote of neonatal rats were measured every week. Time of eye-opening, ear-opening, hair-growing and teething were observed for assessing their physical growth. Reflex and sensory function of neonatal rats, such as planar tuning, spatial turning, visual orientation and auditory surprise was observed at 3, 7, 12, 16 days after birth respectively; The mean targeting time of each cote was used as reference for assessing their feflex. Y-lybirinth test was used for assessing learning and memory function of neonatal rats(30 days after birth).MAIN OUTCOME MEASURES: ① Main outcomes: Reflex and sensory, such as planar tuning, spatial turning, visual orientation and auditory surrise. ② Secondary outcomes: Influence of hyperthemia and cigarette exposure on learning memory function of neonatal rats.RESULTS: For hyperthermia group(41C and 42C), targeting time of neonatal rat physical growth(eye-opening, ear-opening, hair-growing and teething) and reflex sensory function(planar tuning, spatial turning, nvisual orientation and auditory surprise), as well as learning and memory(minute) were obviously delayed in contrast with those of the control group and 37 C group(χ2 = 11.34, P ＜0.01 ); meanwhile, longer hyperthermia exposure (1.5 minutes) combined with cigarette smoke had supplementary effect on the above neural behaviors, which was significantly different from that of single hyperthermia group(χ2=10.29, P＜0.01).CONCLUSION: Abnormal neural behavior of neonatal rats, such as growing retardation, learning and memory obstacle could be induced by the combination of longer hyperthemia exposure and cigarette smoke.