Effects of inosine on axonal regeneration of axotomized retinal ganglion cells in adult rats

Wu, Mei‐Hwan; You, Song; Hou, Bing; Jiao, Xi-Ying; Li, Yao-Yu; Ju, Gong

doi:10.1016/s0304-3940(03)00151-4

Cited by 19 publications

(12 citation statements)

References 14 publications

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“…It is also possible that alterations in Aδ fibers, as reflected by NF200 staining, contributed to the changes in non-voiding contractions observed in our study. As noted earlier, inosine has axogenic and neurotrophic activity [45,46], consistent with an ability to promote regeneration of Aδ fibers. However the extent to which this applies to Aδ fibers in the bladder remains be to determined.…”

Section: Inosinesupporting

confidence: 73%

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

Doyle¹,

Cristofaro²,

Sullivan³

et al. 2018

Cell Physiol Biochem

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Spinal cord injury (SCI) caused by trauma or disease leads to motor and sensory abnormalities that depend on the level, severity and duration of the lesion. The most obvious consequence of SCI is paralysis affecting lower and upper limbs. SCI also leads to loss of bladder and bowel control, both of which have a deleterious, life-long impact on the social, psychological, functional, medical and economic well being of affected individuals. Currently, there is neither a cure for SCI nor is there adequate management of its consequences. Although medications provide symptomatic relief for the complications of SCI including muscle spasms, lower urinary tract dysfunction and hyperreflexic bowel, strategies for repair of spinal injuries and recovery of normal limb and organ function are still to be realized. In this review, we discuss experimental evidence supporting the use of the naturally occurring purine nucleoside inosine to improve the devastating sequelae of SCI. Evidence suggests inosine is a safe, novel agent with multifunctional properties that is effective in treating complications of SCI and other neuropathies.

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Section: Inosinesupporting

confidence: 73%

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

Doyle¹,

Cristofaro²,

Sullivan³

et al. 2018

Cell Physiol Biochem

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“…Thus, administration of inosine in vivo can induce massive sprouting of the normal corticospinal tract into the lesioned side of the cord, 14 stimulate significant axonal rewiring and improve functional outcome after stroke, 28 and protect axotomized retinal ganglion cells from optic nerve transection. 19,20 Inosine is also capable of protecting astrocytes and neurons against hypoxia, ischemia and zinc sulfate in vitro. 15,18,29 The present study demonstrated that inosine could reduce apoptosis after crushing injury of the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16][17][18][19][20][21] These effects kindle the hope for its use in SCI to conquer secondary degeneration. The aim of the present study was to investigate the possible neuroprotective and ameliorating effects and the time window of inosine in an experimental spinal cord clip compression injury model in adult rats.…”

Section: Introductionmentioning

confidence: 99%

Secondary degeneration reduced by inosine after spinal cord injury in rats

et al. 2005

Spinal Cord

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Study design: Assessment of the potential protective effects of inosine on an animal model of spinal cord injury. Objectives: Our previous studies have demonstrated that inosine can directly protect neurons in vitro from zinc-induced injury and axotomized retinal ganglion cells of rats in vivo. This investigation was carried out to examine the possible protective effects of inosine on spinal cord secondary degeneration. Setting: Institute of Neurosciences, The Fourth Military Medical University, Xi'an, China. Methods: Compressive spinal cord injury (95-g load for 1 min) model was established in rats, and inosine was administrated beginning at different time points (2, 12, or 24 h) after spinal cord injury. Results: Using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and hematoxylin and eosin staining, our study demonstrated that administration of inosine as late as 12 h after injury significantly reduced the total volume of spinal cord degenerative areas and the number of apoptotic cells 3 days following the trauma. Conclusion: Inosine can significantly reduce the spread of secondary degeneration and the cell death following spinal cord injury in adult rats. These findings may find a clinical application in the treatment of acute spinal cord injury.

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“…Even though few studies have focused on the physiological roles of inosine, there is a growing body of evidence suggesting that this nucleoside has significant biological effects. It has been suggested that inosine elicits neuroprotective effects in neurons and astrocytes subjected to hypoxia, glucose-oxygen deprivation, and oxidative damage [18,19]; stimulates neurite outgrowth in vitro [20]; and induces axonal outgrowth in vivo and in vitro studies [21][22][23][24][25]. Moreover, systemic administration of inosine causes antinociceptive, antiallodynic, and antihyperalgesic effects in mice [26,27].…”

Section: Introductionmentioning

confidence: 99%

Signaling pathways underlying the antidepressant-like effect of inosine in mice

Gonçalves

Neis

Rieger

et al. 2016

Purinergic Signalling

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Inosine is a purine nucleoside formed by the breakdown of adenosine that elicits an antidepressant-like effect in mice through activation of adenosine A 1 and A 2A receptors. However, the signaling pathways underlying this effect are largely unknown. To address this issue, the present study investigated the influence of extracellular-regulated protein kinase (ERK)1/2, Ca 2+ /calmoduline-dependent protein kinase (CaMKII), protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase 3beta (GSK-3β) modulation in the antiimmobility effect of inosine in the tail suspension test (TST) in mice. In addition, we attempted to verify if inosine treatment was capable of altering the immunocontent and phosphorylation of the transcription factor cyclic adenosine monophosphatate (cAMP) responsebinding element protein (CREB) in mouse prefrontal cortex and hippocampus. Intracerebroventricular administration of U0126 (5 μg/mouse, MEK1/2 inhibitor), KN-62 (1 μg/ mouse, CaMKII inhibitor), H-89 (1 μg/mouse, PKA inhibitor), and wortmannin (0.1 μg/mouse, PI3K inhibitor) prevented the antiimmobility effect of inosine (10 mg/kg, intraperitoneal (i.p.)) in the TST. Also, administration of a subeffective dose of inosine (0.1 mg/kg, i.p.) in combination with a sub-effective dose of AR-A014418 (0.001 μg/mouse, GSK-3β inhibitor) induced a synergic antidepressant-like effect. None of the treatments altered locomotor activity of mice. Moreover, 24 h after a single administration of inosine (10 mg/kg, i.p.), CREB phosphorylation was increased in the hippocampus. Our findings provided new evidence that the antidepressant-like effect of inosine in the TST involves the activation of PKA, PI3K/Akt, ERK1/2, and CaMKII and the inhibition of GSK-3β. These results contribute to the comprehension of the mechanisms underlying the purinergic system modulation and indicate the intracellular signaling pathways involved in the antidepressant-like effect of inosine in a preclinical test of depression.

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Effects of inosine on axonal regeneration of axotomized retinal ganglion cells in adult rats

Cited by 19 publications

References 14 publications

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

Secondary degeneration reduced by inosine after spinal cord injury in rats

Signaling pathways underlying the antidepressant-like effect of inosine in mice

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