Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats

Cui, Shusen; Yang, Christine; Bowen, Rudy; Bai, Ou; Li, Xinmin; Jiang, Wen; Zhang, Xia

doi:10.1016/s0006-8993(03)02699-4

Cited by 50 publications

(41 citation statements)

References 27 publications

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“…Here, we identified the BMP4-mimicking effects of VPA, which could lead to usage of VPA in the control of BMP4-activation-related diseases as well for its identified pharmacological effects such as in treatment of epilepsy (Perucca, 2002). VPA is more commonly known as an inhibitor of histone deacetylases (HDAC) (Hsieh et al, 2004), and has various pharmacological effects including brain tumor suppression, neuroprotection, peripheral nerve injury enhancement, cell cycle arrest, apoptosis, terminal differentiation of neoplastic cells, antiepileptic properties, as well as antineoplastic and antiangiogenesis effects (Cui et al, 2003). In a recent study, BMP4 also was identified as a potential inhibitor of the growth of brain-tumor-initiating cells (Piccirillo et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway

et al. 2009

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Bone morphogenic protein 4 (BMP4), a member of the TGF-β superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/β-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3β (GSK3β) activating the Wnt/β-catenin pathway. The BMP4-mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.

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Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway

et al. 2009

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“…These actions include induction of BDNF expression (Nibuya et al, 1995(Nibuya et al, , 1996Fukumoto et al, 2001;Hashimoto et al, 2002;Altar et al, 2003;Einat et al, 2003), activation of CREB (Nibuya et al, 1996;Chen et al, 1997;Ozaki and Chuang, 1997;Thome et al, 2000;Grimes and Jope, 2001;Einat et al, 2003), increases in numbers and lengths of neuronal processes (Vaidya et al, 1999;Yuan et al, 2001;Williams et al, 2002;Cui et al, 2003) (Fig. 5), and enhancement of neurogenesis (Chen et al, 2000;Malberg et al, 2000;Santarelli et al, 2003) (Figs.…”

Section: Induction Of Neurotrophic or Neurotrophic-related Actions Ismentioning

confidence: 99%

“…2, 3). Recent animal and cell-culture studies demonstrate that valproate enhances axonal regeneration and neuronal survival against a variety of insults (Cui et al, 2003;Dou et al, 2003;Jeong et al, 2003). Valproate may be an appropriate alternative or complementary neurotrophic treatment for brain trauma, ischemia, and neurodegenerative diseases (Loy and Tariot, 2002).…”

Section: Valproate As An Alternative or Complementary Neurotrophic Thmentioning

confidence: 99%

Mood Stabilizer Valproate Promotes ERK Pathway-Dependent Cortical Neuronal Growth and Neurogenesis

Hao¹,

Creson²,

Zhang³

et al. 2004

J. Neurosci.

377

300

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Manic-depressive illness has been conceptualized as a neurochemical illness. However, brain imaging and postmortem studies reveal gray-matter reductions, as well as neuronal and glial atrophy and loss in discrete brain regions of manic-depressive patients. The roles of such cerebral morphological deficits in the neuropathophysiology and therapeutic mechanisms of manic-depressive illness are unknown. Valproate (2-propylpentanoate) is a commonly used mood stabilizer. The ERK (extracellular signal-regulated kinase) pathway is used by neurotrophic factors to regulate neurogenesis, neurite outgrowth, and neuronal survival. We found that chronic treatment of rats with valproate increased levels of activated phospho-ERK44/42 in neurons of the anterior cingulate, a region in which we found valproateinduced increases in expression of an ERK pathway-regulated gene, bcl-2. Valproate time and concentration dependently increased activated phospho-ERK44/42 and phospho-RSK1 (ribosomal S6 kinase 1) levels in cultured cortical cells. These increases were attenuated by Raf and MEK (mitogen-activated protein kinase/ERK kinase) inhibitors. Although valproate affects the functions of GSK-3 (glycogen synthase kinase-3) and histone deacetylase (HDAC), its effects on the ERK pathway were not fully mimicked by selective inhibitors of GSK-3 or HDAC. Similar to neurotrophic factors, valproate enhanced ERK pathway-dependent cortical neuronal growth. Valproate also promoted neural stem cell proliferation-maturation (neurogenesis), demonstrated by bromodeoxyuridine (BrdU) incorporation and double staining of BrdU with nestin, Tuj1, or the neuronal nuclei marker NeuN (neuronal-specific nuclear protein). Chronic treatment with valproate enhanced neurogenesis in the dentate gyrus of the hippocampus. Together, these data demonstrate that valproate activates the ERK pathway and induces ERK pathway-mediated neurotrophic actions. This cascade of events provides a potential mechanism whereby mood stabilizers alleviate cerebral morphometric deficits associated with manic-depressive illness.

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“…Its yearly incidence is 1/1000 [1]. Significant histopathological changes occur after damage occurring due to post-traumatic nerve stretching, crushing and cutting.…”

Section: Introductionmentioning

confidence: 99%

“…Impulse cannot be transmitted to the muscle or sensory organs stimulated by the damaged nerve cell, and a neurological dysfunction develops depending on the affected area [4].Disruption of blood flow due to crushing over the nerve and the presence of reperfusion after the restoration of the damage causes the formation of acute phase reactants (cytokines such as TNF-α and IL-1β) and free oxygen radicals. Furthermore, these cytokines that form in the neuro-inflammation cascade intensify the damage and result in myelin phagocytosis and the prevention of regeneration in damaged nerve cell [5,6].Although the efficiency of neurotrophic drugs, steroids, hormones, low dose radiation and different chemical materials in increasing nerve regeneration is reported today, and the highest level is technically reached in nerve repair with the development of microsurgical techniques, a total recovery cannot be provided in motor and sensory terms in nerve regeneration [1][2][3]7,8]. The peripheral nervous system is more successful in axonal regeneration as inhibitor myelin proteins are less dominant and Schwann cells are more active in distal.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory efficiency of erythropoietin in sciatic nerve damage

Aydın¹

2018

Ann Clin Anal Med

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Aim: Peripheral nerve injuries are the major health problem in the world. Several neurotrophic agents have been evaluated for their efficacy in nerve injury. We aimed to compare the effects of erythropoietin (EPO), known to have neuroprotective, neuroregenerative and anti-inflammatory properties like gabapentin, on the sciatic nerve in experimental crush injury to the sciatic nerve in rats. Material and Method: We classified four groups for this study. Aneurysm clips were used for the sciatic nerve crush injury for trauma groups. Sciatic nerve and blood samples were taken for the experimental procedures. ELISA method was used to evaluate the tissue. Results: Average values of IL-1β and TNF-α levels of the groups and the relationship between the groups are presented. After EPO and gabapentin treatment, IL-1β levels were significantly lower in the trauma group. TNF-α levels were statistically significantly higher in the trauma group than in other groups. According to the EPO and gabapentin treatment, TNF-α levels were significantly lower than those in the trauma group. Discussion: In this study, the effects of EPO and gabapentin on the rat sciatic nerve injury were examined by biochemical methods. EPO is a drug that has an advantage of the treatment of anemia and used for the nerve damage in the experimental studies. We suggest that the EPO has beneficial effects on the trauma models with the blood loss and the nerve damage.

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Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats

Cited by 50 publications

References 27 publications

Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway

Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway

Mood Stabilizer Valproate Promotes ERK Pathway-Dependent Cortical Neuronal Growth and Neurogenesis

Anti-inflammatory efficiency of erythropoietin in sciatic nerve damage

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