Excitotoxic spinal damage induced by kainic acid impairs locomotion, alters nociception, and reduces CREB nuclear translocation.

Our previous in vitro studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while in vitro spinal cord excitotoxicity was produced by bath-applied KA. KA application evoked significant neuronal loss, deterioration in hindlimb motor coordination and thermal allodynia. In addition, immunohistochemical analysis showed that KA application resulted in decreased number of CREB positive nuclei in the ventral horn and in dorsal layers III-IV. Our data suggests that excitotoxic-induced neuronal loss may be potentially predicted by altered CREB nuclear translocation.

Resveratrol evokes neuroprotective effects and improves foot stance following kainate-induced excitotoxic damage to the mouse spinal cord.

Excitotoxicity, characterized by over-activation of glutamate receptors, is a major contributor to spinal cord injury (SCI) pathophysiology, resulting in neuronal death and loss of locomotor function. In our previous in vitro studies, we showed that excitotoxicity induced by the glutamate analogue kainate (KA) leads to a significant reduction in the number of neurons, providing a model for SCI. Our current objective was to assess the neuroprotective role of resveratrol (RESV), a natural polyphenol, following KA-induced SCI. In vivo excitotoxicity was induced by intraspinal injection of KA immediately followed by RESV administration to Balb/C adult male mice. In neonatal mouse spinal cord preparations, excitotoxicity was transiently induced by bath-applied KA, either with or without RESV. KA administration resulted in a significant deterioration in hindlimb motor coordination and balance during locomotion, which was partially reverted by RESV. Additionally, RESV preserved neurons in both dorsal and ventral regions. Sirtuin 2 (SIRT2) immunoreactive signal was increased by RESV, while the selective SIRT1 inhibitor 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (EX-527) attenuated RESV neuroprotective effects. These findings suggest that RESV attenuation of excitotoxic-induced neuronal loss and locomotor deficits is mediated, at least in part, through the activation of SIRT1, potentially involving SIRT2 as well. Indeed, our results highlight the potential use of RESV to enhance neuroprotective strategies for SCI.

Suprapontine Structures Modulate Brainstem and Spinal Networks.

Several spinal motor output and essential rhythmic behaviors are controlled by supraspinal structures, although their contribution to neuronal networks for respiration and locomotion at birth still requires better characterization. As preparations of isolated brainstem and spinal networks only focus on local circuitry, we introduced the in vitro central nervous system (CNS) from neonatal rodents to simultaneously record a stable respiratory rhythm from both cervical and lumbar ventral roots (VRs).Electrical pulses supplied to multiple sites of brainstem evoked distinct VR responses with staggered onset in the rostro-caudal direction. Stimulation of ventrolateral medulla (VLM) resulted in higher events from homolateral VRs. Stimulating a lumbar dorsal root (DR) elicited responses even from cervical VRs, albeit small and delayed, confirming functional ascending pathways. Oximetric assessments detected optimal oxygen levels on brainstem and cortical surfaces, and histological analysis of internal brain structures indicated preserved neuron viability without astrogliosis. Serial ablations showed precollicular decerebration reducing respiratory burst duration and frequency and diminishing the area of lumbar DR and VR potentials elicited by DR stimulation, while pontobulbar transection increased the frequency and duration of respiratory bursts. Keeping legs attached allows for expressing a respiratory rhythm during hindlimb stimulation. Trains of pulses evoked episodes of fictive locomotion (FL) when delivered to VLM or to a DR, the latter with a slightly better FL than in isolated cords.In summary, suprapontine centers regulate spontaneous respiratory rhythms, as well as electrically evoked reflexes and spinal network activity. The current approach contributes to clarifying modulatory brain influences on the brainstem and spinal microcircuits during development. Novel preparation of the entire isolated CNS from newborn rats unveils suprapontine modulation on brainstem and spinal networks. Preparation views (A) with and without legs attached (B). Successful fictive respiration occurs with fast dissection from P0-P2 rats (C). Decerebration speeds up respiratory rhythm (D) and reduces spinal reflexes derived from both ventral and dorsal lumbar roots (E).

Relapse after more than 20 years of follow-up for epithelial ovarian carcinoma.

BACKGROUND: Very late relapse of ovarian cancer is unusual and may present with atypical symptoms. CASES: We diagnosed 3 cases of relapse occurring after more than 20 years of follow-up. In the first case, the first recurrence was diagnosed by an appendicitis syndrome. With the second recurrence, small pelvic nodules were detected by fluorodeoxyglucose scintigraphy, whereas other imaging method results were negative. In the second case, a nodule in the axilla revealed the recurrence, and imaging methods confirmed multiple metastasis. In the third case, the patient presented with paroxysmal abdominal pain, and fluorodeoxyglucose scintigraphy showed a tiny lesion. CONCLUSION: Late relapses of ovarian cancer raise the issue of regrowth of dormant cells or the development of a new primary cancer. The absence of family history and BRCA gene mutations in these 3 patients favor late recurrence. Fluorodeoxyglucose scintigraphy was useful for diagnosis, particularly of small lesions not visible by classic imaging methods.