Vet Med - Czech, 2015, 60(4):186-193 | DOI: 10.17221/8106-VETMED
The effects of inosine on clinical and histological findings after experimental spinal cord injury in ratsOriginal Paper
- 1 University of Veterinary Medicine and Pharmacy, Kosice, Slovak Republic
- 2 Institute of Neurobiology, Slovak Academy of Sciences, Centre of Excellence for Brain Research, Kosice, Slovak Republic
Inosine is a naturally occurring purine nucleoside, the effect of which was discovered only in recent decades. It has potential to prevent neuronal and glial death and can stimulate axonal outgrowth. This study evaluated the effect of inosine (400 mg per rat) administered orally two hours after experimental spinal cord injury and continuously daily for 12 days. We observed the effect of inosine on clinical and histological changes by means of measurement of recovery of hind leg motor function and urinary bladder function, frequency of spasms, neuronal profile and spinal cord tissue sparing. The rats were randomly divided into three groups, SCI-Aqua and SCI-Inosine, with daily administration of aqua for injection or inosine, and SCI-Sham group without spinal injury. The motor function of hind legs and urinary bladder function were evaluated daily for 12 days after the spinal cord injury. In the SCI-Inosine group we recorded lower incidence of spasms due to spinal cord irritation in the early postoperative period when compared to the SCI-Aqua group. We used immunohistochemistry with specific neuronal antibodies to determine the neuronal profiles and the Luxol fast blue staining method to detect the white and grey matter tissue sparing. In our study we recorded significant differences in recovery between the SCI-Aqua and SCI-Inosine group from eighth days after surgery. Moreover, the post mortem investigation of transverse spinal cord sections revealed significantly higher numbers in the SCI-Inosine group (more neurons, greater tissue sparing). According to our findings inosine accelerates the recovery of neurological functions.
Keywords: spinal compression; secondary injury; locomotor function; urinary bladder function; axonal rewiring
Published: April 30, 2015 Show citation
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References
- Basso DM, Beattie MS, Bresnahan JC (1995): A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of Neurotrauma 12, 1-21.
Go to original source...
Go to PubMed...
- Beattie MS, Farooqui AA, Bresnahan JC (2000): Review of current evidence for apoptosis after spinal cord injury. Journal of Neurotrauma 17, 915-925.
Go to original source...
Go to PubMed...
- Benowitz LI, Goldberg DE, Madsen JR, Soni D, Irwin N (1999): Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury. Proceedings of National Academic Science USA 96, 13486-13490.
Go to original source...
Go to PubMed...
- Bohnert DM, Purvines S, Shapiro S, Borgens RB (2007): Simultaneous application of two neurotrophic factors after spinal cord injury. Journal of Neurotrauma 24, 846-863.
Go to original source...
Go to PubMed...
- Coates JR (2000): Intervertebral disk disease. Veterinary Clinics of North America Small Animal Practice 30, 77-110.
Go to original source...
Go to PubMed...
- Conta AC, Stelzner DJ (2008): Immunomodulatory effect of the purine nucleoside inosine following spinal cord contusion injury in rat. Spinal Cord 46, 39-44.
Go to original source...
Go to PubMed...
- Fawcet W (2006): Overcoming inhibition in the damaged spinal cord. Journal of Neurotrauma 23, 371-383.
Go to original source...
Go to PubMed...
- Fawcet W, Asher RA (1999): The glial scar and central nervous system repair. Brian Research Bulletin 49, 377-391.
Go to original source...
Go to PubMed...
- Fehlings MG, Tator CH, Linden RD (1989): The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury. Journal of Neurosurgery 71, 403-416.
Go to original source...
Go to PubMed...
- Gomez G, Sitkovsky MV (2003): Differential requirement for A2a andA3 adenosine receptors for the protective effect of inosine in vivo. Blood 102, 4472-4478.
Go to original source...
Go to PubMed...
- Hasko G, Cronstein BN (2004): Immunomodulatory and neuroprotective effects of inosine. Trends in Pharmaceutical Sciences 25, 152-157.
Go to original source...
Go to PubMed...
- Hasko G, Linden J, Cronstein B, Pacher P (2008): Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nature Reviews: Drug Discovery 7, 759-770.
Go to original source...
Go to PubMed...
- Jurkowitz MS, Litsky ML, Browning MJ, Hohl ChM (1998): Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitochondrial inhibition: correlation between protection and ATP preservation. Journal of Neurochemistry 71, 535-548.
Go to original source...
Go to PubMed...
- Lee YS, Lin ChY, Jiang HH, MacArthur L, McAtee M, Nash C, Bregman BS (2013): Nerve regeneration restores supraspinal control of bladder function after complete spinal cord injury. Journal of Neuroscience 33, 10591-10606.
Go to original source...
Go to PubMed...
- Li GL, Farooque M, Holtz A, Olsson Y (1999): Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord. Acta Neuropathologica (Berlin) 98, 473-480.
Go to original source...
Go to PubMed...
- Litsky ML, Hohl CM, Lucas JH, Jurkowitz MS (1999): Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia. Brain Research 821, 426-432.
Go to original source...
Go to PubMed...
- Liu F, You SW, Yao LP, Liu HL, Jiao XY, Shi M, Z1hao QB, Ju G (2006): Secondary degeneration reduced by inosine after spinal cord injury in rats. Spinal Cord 44, 421-426.
Go to original source...
Go to PubMed...
- Liu F, Yao L, Yuan J, Liu H, Yang X, Qin W, Wu G, Yang L, Wang H, Takahashi N, Yamaguchi O (2009): Protective effects of inosine on urinary bladder function in rats with partial bladder outlet obstruction. Urology 73, 1417-1422.
Go to original source...
Go to PubMed...
- Markowitz CE, Spitsin S, Zimmerman V, Jacobs D, Udupa JK, Hooper DC, Koprowski H (2009): The Treatment of multiple sclerosis with inosine. Journal of Alternative and Complementary Medicine 15, 619-625.
Go to original source...
Go to PubMed...
- Mautes AEM, Weinzierl MR, Donovan F, Noble LJ (2000): Vascular events after spinal cord injury: Contribution to secondary pathogenesis. Physical Therapy 80, 673-687.
Go to original source...
- McKee WM (1990): Spinal trauma in dogs and cats: A review of 51 cases. Veterinary Record 26, 285-289.
- Mubagwa K, Flameng W (2001): Adenosine, adenosine receptors and myocardial protection" an updated overview. Cardiovascular Research 52, 25-39.
Go to original source...
Go to PubMed...
- Park EH, White GA, Tieber LM (2012): Mechanisms of injury and emergency care of acute spinal cord injury in dogs and cats. Journal of Veterinary Emergency and Critical Care 22, 160-178.
Go to original source...
Go to PubMed...
- Petrausch B, Tabibiazar R, Roser T, Jing Y, Goldman D, Stuermer CAO, Irwin N, Benowitz LI (2000): A purinesensitive pathway regulates multiple genes involved in axon regeneration in goldfish retinal ganglion cells. Journal of Neuroscience 20, 8031-8041.
Go to original source...
Go to PubMed...
- Pope MH, Goh KL, Magnuson M (2002): "Spine ergonomics". Annual Review of Biomedicine Engineering 4, 49-68.
Go to original source...
Go to PubMed...
- Schwab ME (2004): Nogo and axon regeneration. Current Opinion in Neurobiology 14, 118-124.
Go to original source...
Go to PubMed...
- Sherwood AM, Graves DE, Priebe MM (2000): Altered motor control and spasticity after spinal cord injury: Subjective and objective assessment. Journal of Rehabilitation Research and Development 37, 41-52.
Go to PubMed...
- Tator CH, Koyanagi I (1997): Vascular mechanisms in the pathophysiology of human spinal cord injury. Journal of Neurosurgery 86, 483-492.
Go to original source...
Go to PubMed...
- Vanicky I, Urdzikova L, Saganova K, Cizkova D, Galik J (2001): Simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. Journal of Neurotrauma 18, 1399-1407.
Go to original source...
Go to PubMed...
- Wakai A, Winter DC, Street JT, O´Sullivan RG, Wang JH, Redmond HP (2001): Inosine attenuates tourniquet-induced skeletal muscle reperfusion injury. Journal of Surgical Research 99, 311-315.
Go to original source...
Go to PubMed...
- Webb AA, Ngan S, Fowler D (2010): Spinal cord injury. II: Prognostic indicators, standards of care and clinical trials. Canadian Veterinary Journal 51, 598-604.
- Wu Z, Liu F, Wang Y, Jiao X, Shi M, Zhao Q, Ju G, You S (2008): Reduced cell death by inosine pretreatment after photochemically induced cerebral ischemia in adult rats. Progress in Natural Science 18, 1513-1518.
Go to original source...
- Yu W, Zacharia LC, Jackson EK, Apodaca G (2006): Adenosine receptor expression and function in bladder uroepithelium. American Journal of Physiology Cell Physiology 291, C254-C265.
Go to original source...
Go to PubMed...
- Zai L, Ferrari Ch, Subbaiah S, Havton LA, Coppola G, Strittmatter S, Irwin N, Geschwind D, Benowitz LI (2009): Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb. Journal of Neuroscience 29, 8187-8197.
Go to original source...
Go to PubMed...
- Zai L, Ferrari C, Dice C, Subbaiah S, Havton LA, Coppola G, Geschwind D, Irwin N, Huebner E, Strittmatter SM, Benowitz LI (2011): Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke. Journal of Neuroscience 31, 5977-5988.
Go to original source...
Go to PubMed...
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