Increased neurosteroids synthesis after brain and spinal cord injury in rats

Michele, Flavia di; Lekieffre, D.; Pasini, Augusto; Bernardi, Giorgio; Bénavidès, J.; Romeo, Elena

doi:10.1016/s0304-3940(00)00965-4

Cited by 56 publications

(28 citation statements)

References 14 publications

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“…These results bring a morphological substrate to previous observations showing progesterone effects in the injured spinal cord (Gonzalez et al 2004;Labombarda et al 2002Labombarda et al , 2003. Although the spinal cord can synthesize its own neurosteroids (di Michele et al 2000;Labombarda et al 2006b;Patte-Mensah et al 2004), supplementary progesterone dosage may be required to produce the above-mentioned effects. After complete spinal transection, changes developed in the nucleus, karyoplasm, and nucleolus.…”

Section: Discussionsupporting

confidence: 80%

Progesterone Effects on Neuronal Ultrastructure and Expression of Microtubule-associated Protein 2 (MAP2) in Rats with Acute Spinal Cord Injury

et al. 2008

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(1) Following acute spinal cord injury, progesterone modulates several molecules essential for motoneuron function, although the morphological substrates for these effects are unknown. (2) The present study analyzed morphological changes in motoneurons distal to the lesion site from rats with or without progesterone treatment. We employed electron microscopy to study changes in nucleus and cytoplasm and immunohistochemistry for the microtubule-associated protein 2 (MAP2) for changes in cytoskeleton. (3) After spinal cord injury, the nucleoplasm appeared more finely dispersed resulting in reduced electron opacity and the nucleus adopted an eccentric position. Changes of perikarya included dissolution of Nissl bodies and dissociation of polyribosomes (chromatolysis). After progesterone treatment for 3 days, the deafferented motoneurons now presented a clumped nucleoplasm, a better-preserved rough endoplasmic reticulum and absence of chromatolysis. Progesterone partially prevented development of nuclear eccentricity. Whereas 50% of injured motoneurons showed nuclear eccentricity, only 16% presented this phenotype after receiving progesterone. Additionally, injured rats showed reduced immunostaining for MAP2 in dendrites, pointing to cytoskeleton abnormalities, whereas progesterone treatment attenuated the injury-induced loss of MAP2. (4) Our data indicated that progesterone maintained in part neuronal ultrastructure, attenuated chromatolysis, and preclude the loss of MAP2, suggesting a protective effect during the early phases of spinal cord injury.

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Section: Discussionsupporting

confidence: 80%

Progesterone Effects on Neuronal Ultrastructure and Expression of Microtubule-associated Protein 2 (MAP2) in Rats with Acute Spinal Cord Injury

et al. 2008

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“…Similarly to what has been observed in CNS [65][66][67][68], in peripheral nerves, the levels of neuroactive steroids are also modified by trauma or pathology. In a crush injury model, the levels of PREG and P metabolites (DHP and THP) evaluated by liquid chromatography-tandem mass spectrometry in the sciatic nerve are decreased by trauma [69].…”

Section: Sexually Dimorphic Changes Of Neuroactive Steroid Levels Indsupporting

confidence: 52%

Neuroactive Steroids and Peripheral Neuropathy

Melcangi

Giatti

Pesaresi

et al. 2011

Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis

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Peripheral neuropathy, either inherited or acquired, is a very common disorder for which effective clinical treatments are not yet available. Neuroactive steroids such as progesterone, testosterone, and their reduced metabolites represent a promising therapeutic option for peripheral neuropathy. Peripheral nerves are able to synthesize and metabolize neuroactive steroids and are a target for these molecules since they express classical and nonclassical steroid receptors. Neuroactive steroids modulate the expression of key transcription factors (TFs) for Schwann cell function, regulate Schwann cell proliferation, and promote the expression of myelin proteins. Interestingly, they are also able to counteract biochemical, morphological, and functional alterations of peripheral nerves in different experimental models of neuropathy, including the alterations caused by aging, diabetic neuropathy, and physical injury. Therefore, neuroactive steroids and pharmacological agents that are able to increase their local synthesis and the synthetic ligands for their receptors offer a promising potential for the treatment of different forms of peripheral neuropathy.

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“…Because GABA is thought to be the pain-related inhibitory transmitter within the CNS, AP may contribute to the mechanisms of antinociception [4]. In addition, previous studies demonstrated that the production of neurosteroids, including AP, is increased after traumatic brain and spinal cord injury [5] or injury caused by chronic constriction of the sciatic nerve [6]. On the basis of these earlier findings, we hypothesized that the pathogenesis of neuropathic pain after painful axotomy involves changes in AP biosynthesis.…”

mentioning

confidence: 90%

Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats

et al. 2011

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The neurosteroid allopregnanolone (AP) influences the excitability of the central nervous system by acting as a positive allosteric modulator of γ-aminobutyric acid type A (GABA(A)) receptors. Here, we investigated the role of AP and its therapeutic potential in rats that showed hyperalgesic behavior after undergoing spinal nerve ligation (SNL). AP levels measured in the spinal cord and brain of rats that underwent SNL were greater than the corresponding levels in control animals. More importantly, spinal AP levels in hyperalgesic rats were lower than those in the rats that did not develop hyperalgesia following SNL; in contrast, brain AP levels were comparable among these groups. No differences in serum AP levels were observed among the groups. In addition, intrathecal exogenous administration of AP showed the antihyperalgesic effects in hyperalgesic rats after SNL. These findings suggest that changes in spinal AP biosynthesis are involved in the pathogenesis of neuropathic pain following peripheral nerve injury, and pharmacological manipulation of this phenomenon may provide a potential therapeutic target for neuropathic pain.

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Increased neurosteroids synthesis after brain and spinal cord injury in rats

Cited by 56 publications

References 14 publications

Progesterone Effects on Neuronal Ultrastructure and Expression of Microtubule-associated Protein 2 (MAP2) in Rats with Acute Spinal Cord Injury

Progesterone Effects on Neuronal Ultrastructure and Expression of Microtubule-associated Protein 2 (MAP2) in Rats with Acute Spinal Cord Injury

Neuroactive Steroids and Peripheral Neuropathy

Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats

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