Semi-automatic method for pre-surgery scoliosis classification on X-ray images using Bending Asymmetry Index.

PURPOSE: Bending Asymmetry Index (BAI) has been proposed to characterize the types of scoliotic curve in three-dimensional ultrasound imaging. Scolioscan has demonstrated its validity and reliability in scoliosis assessment with manual assessment-based X-ray imaging. The objective of this study is to investigate the ultrasound-derived BAI method to X-ray imaging of scoliosis, with supplementary information provided for the pre-surgery planning. METHODS: About 30 pre-surgery scoliosis subjects (9 males and 21 females; Cobb: 50.9 ± 19.7°, range 18°-115°) were investigated retrospectively. Each subject underwent three-posture X-ray scanning supine on a plain mattress on the same day. BAI is an indicator to distinguish structural or non-structural curves through the spine flexibility information obtained from lateral bending spinal profiles. BAI was calculated semi-automatically with manual annotation of vertebral centroids and pelvis level inclination adjustment. BAI classification was validated with the scoliotic curve type and traditional Lenke classification using side-bending Cobb angle measurement (S-Cobb). RESULTS: 82 curves from 30 pre-surgery scoliosis patients were included. The correlation coefficient was R2 = 0.730 (p < 0.05) between BAI and S-Cobb. In terms of scoliotic curve type classification, all curves were correctly classified; out of 30 subjects, 1 case was confirmed as misclassified when applying to Lenke classification earlier, thus has been adjusted. CONCLUSION: BAI method has demonstrated its inter-modality versatility in X-ray imaging application. The curve type classification and the pre-surgery Lenke classification both indicated promising performances upon the exploratory dataset. A fully-automated of BAI measurement is surely an interesting direction to continue our endeavor. Deep learning on the vertebral-level segmentation should be involved in further study.

Developmental regulation of fear learning and anxiety behavior by endocannabinoids.

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid (eCB) system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic eCB signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that eCB signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic eCB signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the eCB system and discuss clinical and rodent models showing eCB regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the eCB system in the central nervous system, and models of pharmacological augmentation of eCB signaling during development in the context of fear learning and anxiety.

Age of stress exposure modulates the immediate and sustained effects of repeated stress on corticolimbic cannabinoid CB1 receptor binding in male rats.

Chronic stress is known to modulate cannabinoid CB1 receptor binding densities in corticolimbic structures, in a region-dependent manner; however, the ontogeny of these changes and the degree to which they recover following exposure to stress have yet to be determined. To this extent, we examined both the immediate and sustained effects (following a 40-day recovery period) of a repeated restraint stress paradigm (30-min restraint/day for 10 days) on CB1 receptor binding in the prefrontal cortex (PFC), hippocampus and amygdala in both adolescent (stress onset at post-natal day [PND] 35) and adult (stress onset at PND 75) male Sprague-Dawley rats. Consistent with previous reports, we found that repeated stress in adult rats resulted in an increase in CB1 receptor binding in the PFC, a reduction in CB1 receptor binding in the hippocampus and no effect in the amygdala. Interestingly, adolescent rats exposed to repeated restraint stress did not show any change in hippocampal CB1 receptor density, but exhibited an upregulation of CB1 receptor binding in both the PFC and amygdala. In adults, a 40-day recovery period resulted in a normalization of CB1 receptor binding in the PFC, and surprisingly a pronounced upregulation of CB1 receptor binding in the hippocampus, possibly indicative of a rebound effect. Adolescents similarly exhibited this rebound increase in hippocampal CB1 receptor binding, despite a lack in immediate downregulation following repeated restraint. Of particular interest, adolescents exposed to stress were found to have a sustained downregulation of prefrontocortical CB1 receptors in adulthood, which may relate to some of the reported sustained behavioral effects of stress in adolescence. Collectively, these data indicate that the effects of chronic stress on cannabinoid CB1 receptor binding are modulated by the age of stress exposure and period of recovery following the cessation of stress.

Timing is everything: evidence for a role of corticolimbic endocannabinoids in modulating hypothalamic-pituitary-adrenal axis activity across developmental periods.

Growing evidence suggests that the endocannabinoid system is vital to ensuring normative maturation of the brain into adulthood. Endocannabinoid signaling contributes to guiding pro-neurogenic processes in early life and the development of neurotransmitter systems. Moreover, there is extensive evidence that recruitment of the endocannabinoid system is crucial in the regulation of neuroendocrine responses to stress via the hypothalamic-pituitary-adrenal (HPA) axis, and contributes to subsequent psychopathological consequences associated with emotionality and anxiety. These stress-induced physiological and behavioural sequelae are regulated by neural structures within the corticolimbic circuit, including the amygdala, hypothalamus, hippocampus, and prefrontal cortex. Based on evidence demonstrating endocannabinoid system involvement in both development and stress-induced changes in HPA axis function, it is reasonable to suggest that endocannabinoid signaling is an important mediator of interactions between stress responsivity and maturational stage. In this review, we discuss the ontogeny of the endocannabinoid system in the central nervous system, clinical and rodent models demonstrating short- and long-term effects of stress exposure, regulation of HPA axis responsivity by endocannabinoid signaling, as well as pharmacological and stress models indicating involvement of the endocannabinoid system in early post-natal and adolescent development on stress reactivity of the HPA, the corticolimbic system, and behaviour.

Estradiol enhances neurogenesis in the dentate gyri of adult male meadow voles by increasing the survival of young granule neurons.

This study investigated whether estradiol influenced the survival of new granule neurons, independent of altering cell proliferation, in the adult rodent dentate gyrus and whether estradiol-induced changes in new neuron number relate to any observed changes in hippocampus-dependent behavior. To test whether estradiol specifically promotes the survival of new neurons we injected castrated adult male meadow voles with the cell synthesis marker bromodeoxyuridine (BrdU; 50 mg/kg) twice on day 0 and then injected either estradiol (10 microg) or vehicle for 5 consecutive days either over days 1-5, days 6-10 or days 11-15 and perfused them on day 16. Estradiol doubled the number of hippocampal BrdU-labeled neurons but only when administered during a discrete period (days 6-10; P< or =0.01) when most new neurons extend their axons [J Comp Neurol 413 (1999) 146]. To test whether the estradiol-induced increase in new neuron number was related to hippocampus-dependent behavior, males were injected with BrdU twice on day 0 and with estradiol or vehicle over days 6-10 before standard Morris water maze training commenced on day 16, 5 days after the final hormone injection. As in the first study, estradiol-treated males had more BrdU-labeled cells than vehicle-treated males. On a probe trial, estradiol-treated males spent significantly more time in the training quadrant than vehicle-treated males despite similar performance between groups during acquisition and reversal training trials. Thus estradiol enhanced the survival of young neurons but only when administered during their 'axon extension' phase and this effect was related to better spatial memory in male voles.

Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats.

In the dentate gyrus of adult female meadow voles, a high dose of estradiol benzoate (EB) increases (within 4 h) then decreases (within 48) the number of dividing progenitor cells (Ormerod BK, Galea LAM. 2001. Reproductive status regulates cell proliferation within the dentate gyrus of the adult female meadow vole: A possible regulatory role for estradiol. Neurosci 2:169-179). We investigated whether time-dependent EB exposure differentially influences the number of new granule cells produced in the adult female rat dentate gyrus and whether EB-stimulated adrenal activity mediates the decrease in cell proliferation. Ovariectomized rats received either an EB (10 microg in 0.1 mL) or vehicle (0.1 mL) injection either 4 or 48 h (Experiment 1) before a BrdU injection (200 mg/kg) and were perfused 24 h later to assess the number of new cells. Relative to vehicle, the number of new cells increased following a 4 h exposure (p < or = 0.04) but decreased following a 48 h exposure (p < or = 0.006) to EB. In Experiment 2, the number of new cells within the dentate gyrus of ovariectomized and adrenalectomized females did not significantly differ between groups exposed to EB versus vehicle for 48 h prior to BrdU administration, suggesting the decreased number of new cells observed within the dentate gyrus of adrenal-intact adult female rats is mediated by EB-stimulated adrenal activity. We conclude that estradiol dynamically regulates cell proliferation within the dentate gyrus of adult female rats in the time-dependent manner observed previously in voles and suppresses cell proliferation by influencing adrenal steroids. Investigating how estradiol dynamically regulates neurogenesis could provide insight into the mechanisms by which the proliferation of progenitor cells is controlled within the adult rodent hippocampus.