Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats

Background Cognitive deficits after perinatal anesthetic exposure are well established outcomes in animal models. This vulnerability is sex-dependent and associated with expression levels of the chloride transporters NKCC1 and KCC2. The hypothesis was that androgen signaling, NKCC1 function, and the age of isoflurane exposure are critical for the manifestation of anesthetic neurotoxicity in male rats. Methods Flutamide, an androgen receptor antagonist, was administered to male rats on postnatal days 2, 4, and 6 before 6 h of isoflurane on postnatal day 7 (ntotal = 26). Spatial and recognition memory were subsequently tested in adulthood. NKCC1 and KCC2 protein levels were measured from cortical lysates by Western blot on postnatal day 7 (ntotal = 20). Bumetanide, an NKCC1 antagonist, was injected immediately before isoflurane exposure (postnatal day 7) to study the effect of NKCC1 inhibition (ntotal = 48). To determine whether male rats remain vulnerable to anesthetic neurotoxicity as juveniles, postnatal day 14 animals were exposed to isoflurane and assessed as adults (ntotal = 30). Results Flutamide-treated male rats exposed to isoflurane successfully navigated the spatial (Barnes maze probe trial F[1, 151] = 78; P < 0.001; mean goal exploration ± SD, 6.4 ± 3.9 s) and recognition memory tasks (mean discrimination index ± SD, 0.09 ± 0.14; P = 0.003), unlike isoflurane-exposed controls. Flutamide changed expression patterns of NKCC1 (mean density ± SD: control, 1.49 ± 0.69; flutamide, 0.47 ± 0.11; P < 0.001) and KCC2 (median density [25th percentile, 75th percentile]: control, 0.23 [0.13, 0.49]; flutamide, 1.47 [1.18,1.62]; P < 0.001). Inhibiting NKCC1 with bumetanide was protective for spatial memory (probe trial F[1, 162] = 6.6; P = 0.011; mean goal time, 4.6 [7.4] s). Delaying isoflurane exposure until postnatal day 14 in males preserved spatial memory (probe trial F[1, 140] = 28; P < 0.001; mean goal time, 6.1 [7.0] s). Conclusions Vulnerability to isoflurane neurotoxicity is abolished by blocking the androgen receptor, disrupting the function of NKCC1, or delaying the time of exposure to at least 2 weeks of age in male rats. These results support a dynamic role for androgens and chloride transporter proteins in perinatal anesthetic neurotoxicity. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

The Effects of Reading Goals on Learning in a Computer Mediated Environment

This study measured the effects of reading goals on learning in a computer mediated environment. Reading goals are defined as the purpose one has for reading. Learning is defined as adding to one’s prior knowledge. A computer mediated environment is defined as reading text from a computer monitor. 125 undergraduates (77 females) were given one of three reading goals: read to understand the text, read to take a test, or read to teach the material to another student. Then the participants read a long (3000+ words) passage of text from a computer screen. A computer program written in Microsoft QuickBasic 4.5 (copyright by Microsoft) presented the text on the screen four lines at a time, and measured how long students spent on each page initially, how many times students re-read pages, and how much time students spent re-reading pages. Half of the participants read passages with headings, while the other half read passages without headings. Learning was measured in three ways: recall of the main topics and supporting details of the passage, time spent reading each page of text and time spent re-reading pages, and number of times pages were re-read. Recall of supporting details was significantly greater for the teaching goal than the testing goal. Time spent re-reading was significantly greater for the teaching goal. Students with the knowing goal recalled significantly more supporting details than students with the testing goal. These findings suggest that reading goals do have an effect on learning in a computer mediated environment.

An Infant Sonicguide Intervention Program for a Child with a Visual Disability

The purpose of the study reported here was to teach a preschool child with a visual impairment and significant developmental delay to reach out and locate objects systematically and accurately from a sitting position and to locate and move toward given objects in the environment using the Infant Sonicguide. Although the child achieved the first goal, time constraints prevented him from reaching the second goal.