Abstract
Background: Attention-deficit hyperactivity disorder (ADHD) is a typical neuropsychiatric disorder characterized by inattention, impulsivity, and hyperactivity, particularly in children. Recent studies demonstrated a close relationship between the development of ADHD and surgery under general anesthesia. However, few studies illustrated if ADHD symptoms changed after surgery. Meanwhile, whether these individuals with natural neural impairment were sensitive to postoperative neurocognitive disorder (PND) still remain unclear. Methods: Spontaneously hypertensive rats (SHR) were utilized as spontaneous ADHD animal model and Wistar-Kyoto (WKY) rats as non-ADHD animal model. We evaluated the variation of neurocognitive function and locomotor activity of the rats undergoing experimental laparotomy with general anesthesia by isoflurane. Neurocognitive function was assessed by fear conditioning test for contextual memory and Morris water maze (MWM) for spatial memory. Depressive-like behavior after surgery was detected by forced swim test, and open-field test and elevated plus maze test were utilized to evaluate locomotor activities and anxiety. Furthermore, we compared electroencephalogram (EEG) signal in ADHD and WKY rats under free-moving conditions. Afterward, c-Fos staining was also utilized to detect the excitatory activity of neurons in these rats to explore the neural mechanism. Results: Locomotor activity of SHR assessed by average speed and number of line crossings in the open-field test decreased 1 week after surgery under general anesthesia, but there was no difference concerning anxiety levels between SHR and WKY rats after surgery. This phenomenon was also paralleled with the change in EEG signal (delta band 0∼3 Hz). Surgery under general anesthesia had no effect on spatial and contextual memory, while it improved spontaneous depression in SHR. The expression of c-Fos was downregulated for at least 1 week in the nucleus accumbens (NAc) area of ADHD rats’ brain after surgery. Conclusion: ADHD rats were not sensitive to PND. Surgery with general anesthesia could partly improve the hyperactivity symptom of ADHD rats. This mechanism was related to the suppression of neural activity in the cerebral NAc of ADHD rats induced by general anesthetics.
Highlights
Attention-deficit hyperactivity disorder (ADHD) is a typical and heterogeneous neuropsychiatric disorder characterized by impaired levels of hyperactivity, impulsivity, and inattention [1], which affects children in particular
Experimental Laparotomy Reduced Locomotor Activity in spontaneously hypertensive rats (SHR) and Had No Effect on Anxiety. We used both SHR and WKY rats to investigate the variation of locomotor activity and emotion after surgery, especially in ADHD individuals
We observed that surgery could reduce the immobility time of SHR in the forced swim test, suggesting that surgery with general anesthesia could improve depression of SHR (Figure 2E; *P = 0.0172, No Surgery vs. Surgery in SHR). These results indicated that SHR were not susceptible to postoperative neurocognitive disorder (PND) whereas surgery with general anesthesia was safe for ADHD patients
Summary
Attention-deficit hyperactivity disorder (ADHD) is a typical and heterogeneous neuropsychiatric disorder characterized by impaired levels of hyperactivity, impulsivity, and inattention [1], which affects children in particular. In 2016, the US Food and Drug Administration issued a warning regarding impaired brain development in children following exposure to certain anesthetic agents used for general anesthesia, namely, the inhalational anesthetics isoflurane, sevoflurane, and desflurane and the intravenous agents propofol and midazolam, in the third trimester of pregnancy [5]. Few studies had illustrated if the symptom of ADHD changed following surgery [6] Whether these individuals with natural neural impairment were sensitive to perioperative neural disorder still remained unclear. Few studies illustrated if ADHD symptoms changed after surgery Whether these individuals with natural neural impairment were sensitive to postoperative neurocognitive disorder (PND) still remain unclear
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