We know from the fluorogold data and the caspase-3 data that the right control retinas of both Ringer's- and VPA-treated rats had similar RGC densities and the same low quantity of caspase activity. We thus assume that these cells have the same vitality. The finding that even the control retinal explants of VPA treated rats regenerated more axons in culture might be indicative of a direct action of VPA on neurite outgrowth.
In damaged RGC, different interpretations are possible. HDAC inhibitors have also been shown to activate the ERK pathway, 13 , 47 thereby enhancing axonal regeneration and neuronal survival. VPA is a well established substance for the long-term treatment of epilepsy and is generally well tolerated.
The most common side effects are somnolence and fatigue, which were apparent to a lesser extent in the rats during sc therapy in this investigation. Changes in visual function have recently been studied extensively in animals and in epilepsy patients treated with different antiepileptic drugs. In the literature, VPA's effect on retinal function is controversially discussed. Goto et al. Other reports stated that VPA can cause significantly impaired color perception in patients.
Furthermore, morphologic retinal alterations modifications of retinal nerve fiber layer or macular thickness have not been reported in patients after 1 year of VPA treatment. We have demonstrated for the first time that VPA administered at a clinically-relevant dosage significantly delayed cell death in injured rat RGC and stimulated RGC axons to regrow in vitro.
Alterations were observed in several pathways thought to be critical in VPA activity; however, the precise mechanism or pathway of VPA-mediated protection is yet unclear, as previously described VPA-mediated hyperacetylation via HDAC inhibition was not reproduced in this investigation. Further experiments needs to investigate which proteins and transcription factors are critically involved in VPA-mediated neuroprotection.
Furthermore, studies in chronic optic nerve injury models e. Disclosure: J. Biermann , None; P. Grieshaber , None; U.
Goebel , None; G. Martin , None; S. Thanos , None; S. Di Giovanni , None; W. Rogawski MA Loscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain. Brain Res. Lithium and valproate decrease inositol mass and increase expression of the yeast INO1 and INO2 genes for inositol biosynthesis.
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Neuropeptides in neuroprotection and neuroregeneration pdf
Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. Cytoarchitecture of the retinal ganglion cells in the rat. In vitro regeneration of adult rat ganglion cell axons from retinal explants. Exp Brain Res.
Survival and axonal elongation of adult rat retinal ganglion cells. Eur J Neurosci. Benowitz LI Routtenberg A. GAP an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. Brain-derived neurotrophic factor modulates GAP but not T alpha1 expression in injured retinal ganglion cells of adult rats. J Neurosci Res. J Neurobiol.
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Robinson GA. Immediate early gene expression in axotomized and regenerating retinal ganglion cells of the adult rat. Regeneration of retinal ganglion cell axons in organ culture is increased in rats with hereditary buphthalmos. Exp Eye Res. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats.