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1.
Neuropharmacology ; 250: 109906, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38494123

ABSTRACT

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.


Subject(s)
Neuroprotective Agents , Spinal Cord Injuries , Animals , Mice , Male , Kainic Acid/toxicity , Spinal Cord , Motor Neurons , Resveratrol/pharmacology , Sirtuin 1 , Sirtuin 2/pharmacology
2.
Cell Mol Neurobiol ; 43(6): 2831-2856, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36732488

ABSTRACT

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).


Subject(s)
Brain Stem , Spinal Cord , Rats , Animals , Animals, Newborn , Rats, Sprague-Dawley , Electric Stimulation , Brain Stem/physiology
3.
Obstet Gynecol ; 103(5 Pt 2): 1082-4, 2004 May.
Article in English | MEDLINE | ID: mdl-15121615

ABSTRACT

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.


Subject(s)
Cystadenocarcinoma, Serous/complications , Neoplasm Recurrence, Local/diagnosis , Ovarian Neoplasms/complications , Abdominal Pain/etiology , Adult , Appendicitis/etiology , Axilla , Cystadenocarcinoma, Serous/diagnosis , Cystadenocarcinoma, Serous/secondary , Diagnostic Imaging , Female , Fluorodeoxyglucose F18 , Follow-Up Studies , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Radiopharmaceuticals , Time Factors
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