EFFECT OF AMINOGUANIDINE ON SPINAL CORD EDEMA OF ACUTE SPINAL CORD INJURY IN RATS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

FAN Zhongkai ¹ , CAO Yang ¹ , ZHANG Zhe ² , WANG Yansong ¹ , YU Deshui ¹ , ZHANG Mingchao ¹ , MEI Xifan ¹ , LUuml ¹

1Department of Orthopedics, First Affiliated Hospital, Liaoning Medical College, Jinzhou Liaoning, 121001, P.R.China;;
2Department of Orthopaedics, Jinzhou 2th Hospital. Corresponding author: LÜ;
Gang, E-mail: ganglv_sy@163.com;

Corresponding author：

Keywords：

Acute spinal cord injury; Spinal cord edema; Aminoguanidine; Aquaporins 4; Rat

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Objective Aminoguanidine (AG) can reduce brain edema and increase the recovery of neuron functions in surgical brain injury and stroke. To investigate the effect of AG on spinal cord injury (SCI) in rats and its mechanism. Methods A total of 150 adult male Sprague Dawley rats (weighing, 230-255 g) were divided into control group (group A, 25 rats without treatment), the sham-operated group (group B, 25 rats undergoing laminectomy), SCI group (group C, 25 SCI rats with injection of 5%DMSO), SCI + AG groups (groups D, E, and F, 25 SCI rats and AG injection of 75, 150, and 300 mg/kg, respectively). The optimal dosage of AG was screened by dry-wet weight method with the percentage of water content at 0, 12, 24, and 48 hours after injury. The blood-spinal cord barriar permeability was further detected by Evans blue (EB) method, aquaporins 4 (AQP4) mRNA expression by RT-PCR, AQP4 protein expression by immunohistochemistry and Western blot. Results AG injection at dosage of 150 mg/kg can significantly reduce edema of spinal cords at 12, 24, and 48 hours after SCI (P lt; 0.05), so 150 mg/kg was the optimal dosage. The EB content in group E was significantly lower than that in group C at 12, 24, and 48 hours after SCI, and the permeability of blood-spinal cord barrier was significantly decreased compared with group C (P lt; 0.05). The AQP4 mRNA expressions in groups B and E were significantly lower than that in group C at 12, 24, and 48 hours after SCI (P lt; 0.05). AQP4 protein expressions in groups B and E were significantly lower than that in group C at 24 and 48 hours after SCI (P lt; 0.05) by Western blot. Immunohistochemical staining revealed that AQP4 protein expression in group C was significantly higher than that in groups B and E (P lt; 0.05) at 48 hours after SCI, but no significant difference was found between group B and group E (P gt; 0.05). Conclusion AG injection at dosage of 150 mg/kg can induce spinal cord edema and injury in rats, which could be correlated with the down-regulation of AQP4 expression.

Citation： FAN Zhongkai,CAO Yang,ZHANG Zhe,WANG Yansong,YU Deshui,ZHANG Mingchao,MEI Xifan,LUuml,Gang. EFFECT OF AMINOGUANIDINE ON SPINAL CORD EDEMA OF ACUTE SPINAL CORD INJURY IN RATS. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(8): 984-988. doi: Copy

1.	Yang YB, Piao YJ. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin, 2003, 24(7): 703-710.
2.	Verkman AS, Ratelade J, Rossi A, et al. Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica. Acta Pharmacol Sin, 2011, 32(6): 702-710.
3.	Wang YF, Fan ZK, Cao Y, et al. 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury. Brain Res, 2011, 1370: 220-226 .
4.	Sun M, Zhao Y, Gu Y, et al. Neuroprotective actions of aminoguanidine involve reduced the activation of calpain and caspase-3 in a rat model of stroke. Neurochem Int, 2010, 56(4): 634-641.
5.	Hao W, Wu XQ, Xu RT. The molecular mechanism of aminoguanidine-mediated reduction on the brain edema after surgical brain injury in rats. Brain Res, 2009, 1282: 156-161.
6.	Xu WB, Lv G, Wang YF, et al. Combination of dexamethasone and aminoguanidine reduces secondary damage in compression spinal cord injury. Cell Mol Neurobiol, 2009, 29(5): 683-689.
7.	Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med, 2000, 6(2): 159-163.
8.	Marsala M, Hefferan MP, Kakinohana O, et al. Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. J Neurotrauma, 2005, 22(11): 1348-1361.
9.	Huang WL, George KJ, Ibba V, et al. The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. Eur J Neurosc, 2007, 25(2): 362-372.
10.	Yu Y, Matsuyama Y, Nakashima S, et al. Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury. Neuroreport, 2004, 15(13): 2103-2107.
11.	Di F, Yan-Ting G, Hui L, et al. Role of aminoguanidine in brain protection in surgical brain injury in rat. Neurosci Lett, 2008, 448(2): 204-207.
12.	Xu M, Su W, Xu QP. Aquaporin-4 and traumatic brain edema. Chin J Traumatol, 2010, 13(2): 103-110.
13.	Yang B, Zador Z, Verkman AS. Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem, 2008, 283(22): 15280-15286.
14.	Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol, 2007, 22(6): 778-784.
15.	Nesic O, Lee J, Ye Z, et al. Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Neuroscience, 2006, 143(3): 779-792.
16.	Saadoun S, Bell BA, Verkman AS, et al. Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain, 2008, 131(Pt 4): 1087-1098.
17.	Galea E, Regunathan S, Eliopoulos V, et al. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J, 1996, 316(Pt 1): 247-249.
18.	Zhu SM, Xiong XX, Zheng YY, et al. Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent pathway in an astrocyte model of cerebral ischemia/reoxygenation. Anesth Analg, 2009, 109(5): 1493-1499.
19.	Tang Y, Cai D, Chen Y. Thrombin inhibits aquaporin 4 expression through protein kinase C-dependent pathway in cultured astrocytes. J Mol Neurosci, 2007, 31(1): 83-93.
20.	Gunnarson E, Zelenina M, Axehult G, et al. Identification of a molecular target for glutamate regulation of astrocyte water permeability. Glia, 2008, 56(6): 587-596.

1. Yang YB, Piao YJ. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin, 2003, 24(7): 703-710.
2. Verkman AS, Ratelade J, Rossi A, et al. Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica. Acta Pharmacol Sin, 2011, 32(6): 702-710.
3. Wang YF, Fan ZK, Cao Y, et al. 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury. Brain Res, 2011, 1370: 220-226 .
4. Sun M, Zhao Y, Gu Y, et al. Neuroprotective actions of aminoguanidine involve reduced the activation of calpain and caspase-3 in a rat model of stroke. Neurochem Int, 2010, 56(4): 634-641.
5. Hao W, Wu XQ, Xu RT. The molecular mechanism of aminoguanidine-mediated reduction on the brain edema after surgical brain injury in rats. Brain Res, 2009, 1282: 156-161.
6. Xu WB, Lv G, Wang YF, et al. Combination of dexamethasone and aminoguanidine reduces secondary damage in compression spinal cord injury. Cell Mol Neurobiol, 2009, 29(5): 683-689.
7. Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med, 2000, 6(2): 159-163.
8. Marsala M, Hefferan MP, Kakinohana O, et al. Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. J Neurotrauma, 2005, 22(11): 1348-1361.
9. Huang WL, George KJ, Ibba V, et al. The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. Eur J Neurosc, 2007, 25(2): 362-372.
10. Yu Y, Matsuyama Y, Nakashima S, et al. Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury. Neuroreport, 2004, 15(13): 2103-2107.
11. Di F, Yan-Ting G, Hui L, et al. Role of aminoguanidine in brain protection in surgical brain injury in rat. Neurosci Lett, 2008, 448(2): 204-207.
12. Xu M, Su W, Xu QP. Aquaporin-4 and traumatic brain edema. Chin J Traumatol, 2010, 13(2): 103-110.
13. Yang B, Zador Z, Verkman AS. Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem, 2008, 283(22): 15280-15286.
14. Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol, 2007, 22(6): 778-784.
15. Nesic O, Lee J, Ye Z, et al. Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Neuroscience, 2006, 143(3): 779-792.
16. Saadoun S, Bell BA, Verkman AS, et al. Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain, 2008, 131(Pt 4): 1087-1098.
17. Galea E, Regunathan S, Eliopoulos V, et al. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J, 1996, 316(Pt 1): 247-249.
18. Zhu SM, Xiong XX, Zheng YY, et al. Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent pathway in an astrocyte model of cerebral ischemia/reoxygenation. Anesth Analg, 2009, 109(5): 1493-1499.
19. Tang Y, Cai D, Chen Y. Thrombin inhibits aquaporin 4 expression through protein kinase C-dependent pathway in cultured astrocytes. J Mol Neurosci, 2007, 31(1): 83-93.
20. Gunnarson E, Zelenina M, Axehult G, et al. Identification of a molecular target for glutamate regulation of astrocyte water permeability. Glia, 2008, 56(6): 587-596.

Chinese Journal of Reparative and Reconstructive Surgery

EFFECT OF AMINOGUANIDINE ON SPINAL CORD EDEMA OF ACUTE SPINAL CORD INJURY IN RATS

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