The role of gait analysis in treating gait abnormalities in cerebral palsy.

Individuals with cerebral palsy (CP) cannot take a normal activity like walking for granted. CP is the most common pediatric neurologic disorder, with an incidence of 3.6 per 1000 live births. The current trend in the treatment of individuals with CP is to perform a thorough evaluation including a complete patient history from birth to present, a comprehensive physical examination, appropriate radiographs, consultation with other medical specialists, and analysis of gait.

Few effects of multi-generational dietary exposure to genistein or nonylphenol on sodium solution intake in male and female Sprague-Dawley rats.

Previous work in our laboratory indicated that lifelong dietary exposure to estrogen-like endocrine disrupters increased sodium solution intake in adult male and female rats. Here, we sought to discern the critical periods necessary for this alteration as well as establish the effects of lower dietary concentrations of genistein and nonylphenol. Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-free chow containing 0, 5, 100, or 500 ppm genistein (approximately equal to 0.0, 0.4, 8.0, and 40.0 mg/kg/day) or 0, 25, 200, or 750 ppm nonylphenol (approximately equal to 0.0, 2.0, 16.0, and 60.0 mg/kg/day). Rats were mated within treatment groups and offspring (F1) maintained on the same diets. Mating for the F1, F2, and F3 (genistein only) was within treatment groups. At postnatal day (PND) 21, the F3 generation began to consume unadulterated phytoestrogen-free chow such that genistein exposure occurred only in utero and preweaning. The F4 generation was never directly exposed to genistein. On PNDs 65-68, intake of regular water and a 3.0% sodium chloride solution was measured for F1-F4 generations (genistein portion) or F1-F2 (nonylphenol portion). Although body weights were decreased by the highest dietary concentrations of genistein and nonylphenol, there were only minimal effects of exposure on sodium solution intake. As expected, intake was highest in female rats. With previous data, these results indicate that the dietary concentrations necessary to increase adult sodium solution intake in rats are greater than 500 ppm genistein and 750 ppm nonylphenol and such effects do not appear to increase across generations.

Dietary ethinyl estradiol exposure during development causes increased voluntary sodium intake and mild maternal and offspring toxicity in rats.

Exogenous estrogen exposure during development often results in behavioral masculinization and/or defeminization of genetic females. Genetic males may be defeminized, hypermasculinized or even demasculinized after similar treatment. Here, pregnant Sprague-Dawley rats consumed phytoestrogen-free diets containing 0, 1, 5 or 200 ppb EE(2) beginning on gestational day (GD) 7. Offspring were weaned to the same maternal diet and maintained gonadally intact. There were mild effects on body weight and food consumption in dams of the 200 ppb group and their offspring weighed less at birth than those of the control group; however, gross assessments of nursing behavior were normal in all dietary groups. Postweaning, offspring of the 200 ppb group weighed less and consumed less food than controls. There were no EE(2)-related effects on open-field activity (tested at postnatal days (PND) 22-24, 43-45 and 64-66), play behavior (tested at PND 35), running wheel activity (PND 63-77) or intake of a 0.3% saccharin-flavored solution (PND 69-71). Intake of a 3.0% sodium chloride-flavored solution on PND 73-75 was increased in both male and female offspring of the 200 ppb group relative to same-sex controls, an effect that is reportedly estrogen mediated. Sodium chloride-flavored solution intake is a sexually dimorphic behavior for which female rats consume more than males. Here, while EE(2) exposure had few effects on the conventional tests of sexually dimorphic behaviors, exposure to 200 ppb in the diet appeared to feminize genetic males and hyperfeminize genetic females with regard to sodium intake.

Multigenerational exposure to dietary nonylphenol has no severe effects on spatial learning in female rats.

Nonylphenol is a common intermediate in the production of many consumer compounds and reportedly acts as an estrogen mimic. Because estrogen affects the spatial learning and memory in rats, the effects of nonylphenol exposure on the performance of female rats in the Morris water maze were investigated. Here, Sprague-Dawley rats (F0) consumed soy-free diets containing 0, 25, 200 or 750 ppm nonylphenol (0, 2, 16 or 60 mg/kg per day) beginning on postnatal day (PND) 42 and continuing for two generations (F1 and F2) with breeding occurring within treatments. Females to be behaviorally tested (n = 7-8 per treatment per generation) were ovariectomized at adulthood and assessed for spatial learning and memory between PND 125-150 (young adult age). Each rat was tested for four consecutive days (three trials per day) in the Morris water maze with the platform in a fixed location. One week later, each subject was primed with estrogen and progesterone and assessed on a single day (three trials). The F1 rats continued on the same diets until PND 380-395 (middle aged) when they were re-tested as above (four consecutive days followed 1 week later with hormonal priming and a single test day). Latency to find the platform, path length and swim speed were averaged over the three trials per day and analyzed using repeated measures analyses of variance. There were no consistent effects of dietary nonylphenol exposure and no interactions of nonylphenol exposure on any measure of performance in either generation at the young age nor at the middle age in the F1 generation. When tested at the young adult age, however, hormone priming resulted in latencies and path lengths that were significantly shorter than in those exhibited during the unprimed test days, and there was no such effect when tested at middle age. Middle aged rats exhibited better performance than the same animals tested at a young age, likely as a result of familiarity and practice with the test paradigm. These data suggest that multigenerational dietary nonylphenol exposure does not cause gross alterations in Morris water maze performance in young adult or middle aged ovariectomized female rats.

Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine-stimulated striatal dopamine release in male and female rats.

Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in the adult female rat striatum. The isoflavone found in soybeans, genistein, is a phytoestrogen and may have comparable effects on striatal DA levels. Similarly, the industrial intermediate and potential endocrine disrupter, para-nonylphenol, has estrogen-like effects. Here, Sprague-Dawley rats were continuously exposed to phytoestrogen-free diets containing 0, 100, or 500 ppm genistein (Experiment 1) or 0 or 200, or 750 ppm nonylphenol (Experiment 2) beginning at conception and continuing throughout. To eliminate estrous cycle influences on DA levels, females were ovariectomized at adulthood. As adults, striatal levels of DA and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were measured in unanesthetized male and female rats via cerebral microdialysis before and for 200 min after an intraperitoneal injection of 2 mg/kg D-amphetamine. Although baseline 5-hydroxyindoleacetic acid (5-HIAA) levels indicated an isolated effect in genistein-treated females, there were no meaningful differences among treatment groups in baseline levels of DA, DOPAC, or HVA. However, dietary exposure to 500 ppm genistein significantly potentiated amphetamine-stimulated DA release in males and a similar trend was apparent, but not statistically significant, in females. Dietary exposure to 200 or 750 ppm nonylphenol had no significant effects in males or females. These results suggest that dietary genistein exposure may act similarly to estradiol in augmenting amphetamine-stimulated DA release.

Sexually dimorphic effects of NMDA receptor antagonism on brain-pituitary-gonad axis development in the platyfish.

The N-methyl-D-aspartate glutamate receptor (NMDAR) is found in hypothalamic nuclei involved in the regulation of reproduction in several species of mammals and fishes. NMDAR is believed to affect reproductive development and function by regulating gonadotropin releasing hormone (GnRH)-producing cells. These pathways are likely to be sexually dimorphic, as are several other neurotransmitter systems involved in reproductive function. In this report, male and female platyfish received intraperitoneal injections of 0, 5, 10, 20, 40 or 60 microg/g body wt. of the non-competitive NMDAR antagonist MK-801. Injections began at 6 weeks of age and continued thrice weekly until control animals reached puberty, as evidenced by anal fin maturation. The percent of pubescent animals was significantly affected by sex and treatment, with fewer MK-801-injected females in puberty than control females at each dose (P<0.001), and fewer pubescent females than males at 10, 20 and 40 microg/g (P<0.05). There were no MK-801-related effects in males. Histological analyses revealed typical immature gonads and pituitary glands in treated females, and typical mature morphology in control females and all males. Immunocytochemical distribution of the R1 subunit of the NMDAR within the brain-pituitary-gonad (BPG) axis was limited to GnRH-containing brain cells in all animals; however, NMDAR1 distribution was in an immature pattern in treated females and a mature pattern in all others. Neural concentrations of GnRH were unaffected by MK-801 treatment in both sexes. These data suggest that in the platyfish, NMDAR influence on reproductive development is sexually dimorphic and occurs at, or above, the level of GnRH-containing cells of the BPG axis.