Investigation of the neuroprotective effect of kefir in experimental spinal cord injury

Abstract

In this study, the antioxidant, anti-inflammatory, and neuroprotective effects of kefir were investigated in spinal cord injury that was experimentally created on rats with a compression trauma model. A total of 56 Wistar-Albino male rats were used in the study. Daily freshly prepared 18 ml/kg/day of kefir was given by oral gavage to animals 7 days before and during the trauma and during the trauma. Spinal cord injury was created according to the weight drop method. On the 1st and 7th days before euthanasia, intracardiac blood was collected for analysis, and then they were sacrificed. The damaged spinal cord segments were examined biochemically, immunohistochemically, and histopathologically. When compared to the sham groups, kefir had a positive effect in the preconditioning and treatment groups by decreasing spinal cord bleeding, edema, myelin sheath damage, liquefactive necrosis, neuronal necrosis, selectivity of canalis centralis, and gitter cell levels significantly. When compared to the sham groups, kefir was found to have a positive effect in the treatment groups by decreasing the neuron specific enolase (NSE), ionized calcium binding adapter molecule 1 (IBA-1), inducible nitric oxide synthase (INOS), cyclooxygenase 2 (COX-2) and myelin basic protein (MBP) levels significantly on the 1st and 7th days, and by increasing the glial fibrillary acidic protein (GFAP) level significantly. As a result, it was demonstrated that kefir had a protective and therapeutic effect on spinal cord injury. 

Keywords

• Kefir
• neuroprotective agents
• spinal cord injuries

References

1. Banji OJ, Banji D, Ch K (2014): Curcumin and hesperidin improve cognition by suppressing mitochondrial dysfunction and apoptosis induced by D-galactose in rat brain. Food Chem Toxicol, 74, 51-59.
2. Bathina S, Das UN (2015): Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci, 11, 1164.
3. Binder DK, Scharfman HE (2004): Brain-derived neurotrophic factor. Growth Factors, 22, 123.
4. Delen E, Durmaz R, Oglakci A, et al (2015): Efficacy of kefir on the release of lysosomal proteases after expremintal spinal cord trauma. J Clin Anal Med, 6, 21-25.
5. Duitschaever C, Kemp N, Emmons D (1987): Pure culture formulation and procedure for the production of kefir. Milchwiss, 42, 80-82.
6. Eddleston M, Mucke L (1993): Molecular profile of reactive astrocytes—implications for their role in neurologic disease. Neurosci, 54, 15-36.
7. Eng LF, Ghirnikar RS (1994): GFAP and astrogliosis. Brain Pathol, 4, 229-237.
8. Erdem H, Oktay M, Yildirim U, et al (2013): Expression of AEG-1 and p53 and their clinicopathological significance in malignant lesions of renal cell carcinomas: a microarray study. Pol J Pathol, 64, 28-32.

9. Font-Nieves M, Sans-Fons MG, Gorina R, et al (2012): Induction of COX-2 enzyme and down-regulation of COX-1 expression by lipopolysaccharide (LPS) control prostaglandin E2 production in astrocytes. J Biol Chem, 287, 6454-6468.
10. Friques AG, Santos FD, Angeli DB, et al (2020): Bisphenol A contamination in infant rats: molecular, structural, and physiological cardiovascular changes and the protective role of kefir. J Nutr Biochem, 75, 108254.
11. Furukawa N, Matsuoka A, Yamanaka Y (1990): Effects of orally administered yogurt and kefir on tumor growth in mice. J Jpn Soc Nutr Food Sci, 43, 450-453.
12. Gale K, Kerasidis H, Wrathall JR (1985): Spinal cord contusion in the rat: behavioral analysis of functional neurologic impairment. Exp Neurol, 88, 123-134.
13. Gao J, Ding G, Li Q, et al (2019): Tibet kefir milk decreases fat deposition by regulating the gut microbiota and gene expression of Lpl and Angptl4 in high fat diet-fed rats. Food Res Int, 121, 278-287.
14. Gopez JJ, Yue H, Vasudevan R, et al (2005): Cyclooxygenase-2-specific inhibitor improves functional outcomes, provides neuroprotection, and reduces inflammation in a rat model of traumatic brain injury. Neurosurg, 56, 590-604.
15. Guo R, Overman M, Chatterjee D, et al (2014): Aberrant expression of p53, p21, cyclin D1, and Bcl2 and their clinicopathological correlation in ampullary adenocarcinoma. Hum Pathol, 45, 1015-1023.
16. Gurcan O, Gurcay AG, Kazanci A, et al (2017): Effect of asiatic acid on the treatment of spinal cord injury: An Experimental study in rats. Turk Neurosurg, 27, 259-264.
17. Guven M, Akman T, Yener AU, et al (2015): The neuroprotective effect of kefir on spinal cord ischemia/reperfusion injury in rats. J Korean Neurosurg Soc, 57, 335.
18. Hanci V, Kerimoğlu A, Koca K, et al (2010): The biochemical effectiveness of N-acetylcysteine in experimental spinal cord injury in rats. Turk J Trauma Emerg Surg, 16, 15-21.
19. Haque A, Ray SK, Cox A, et al (2016): Neuron specific enolase: a promising therapeutic target in acute spinal cord injury. Metab Brain Dis, 31, 487-495.
20. Hewett SJ, Bell SC, Hewett JA (2006): Contributions of cyclooxygenase-2 to neuroplasticity and neuropathology of the central nervous system. Pharmacol Ther, 112, 335-357.
21. Huang EJ, Reichardt LF (2001): Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci, 24, 677-736.
22. Imai Y, Kohsaka S (2002): Intracellular signaling in M‐CSF‐induced microglia activation: role of Iba1. Glia, 40, 164-174.
23. Jia Y, Lu T, Yao S, et al (2019): The effects of interferon-β on neuronal apoptosis and the expressions of BDNF and TrkB in rats with spinal cord injuries. Int J Clin Exp Med, 12,12693-12701.
24. Kato K (2012): Stem cells in human normal endometrium and endometrial cancer cells: characterization of side population cells. Kaohsiung J Med Sci, 28, 63-71.
25. Kavakli HS, Koca C, Alici O (2011): Antioxidant effects of curcumin in spinal cord injury in rats. Turk J Trauma Emerg Surg, 17, 14-18.
26. Kubo M, Odani T, Nakamura S, et al (1992): Pharmacological study on kefir--a fermented milk product in Caucasus. I. On antitumor activity (1). Yakugaku Zasshi, 112, 489-495.
27. Matsuu M, Shichijo K, Okaichi K, et al (2003): The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats. J Radiat Res, 44, 111-115.
28. Miller AD, Westmoreland SV, Evangelous NR, et al (2012): Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis). J Med Primatol, 41, 202-209.
29. Mumford A (2007): An Investigation into the spatial organization of kefir grains. Microb Divers, 1-11.
30. Özsoy S (2016): The Protective Effect of Kefir on Carbon Tetrachloride-induced Histopathological Changes in the Livers of Rats. Kafkas Univ Vet Fak Derg, 22, 403-408.
31. Resnick DK, Graham SH, Dixon CE, et al (1998): Role of cyclooxygenase 2 in acute spinal cord injury. J Neurotrauma, 15, 1005-1013.
32. Rollason V, Flora Samer C, Daali Y, et al (2014): Prediction by pharmacogenetics of safety and efficacy of non-steroidal anti-inflammatory drugs: a review. Curr Drug Metab, 15, 326-343.
33. Serarslan Y, Yönden Z, Özgiray E, et al (2010): Protective effects of tadalafil on experimental spinal cord injury in rats. J Clin Neurosci, 17, 349-352.
34. Siebels á, Rohrmann K, Oberneder R, et al (2011): A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients. World J Urol, 29, 121-126.
35. Sirin Y, Keles H, Besalti O, et al (2012): Comparison of ATP-MgCl2 and methylprednisolone in experimentally induced spinal cord trauma. J Clin Anal Med, 3, 442-447.
36. St-Onge M-P, Farnworth ER, Jones PJ (2000): Consumption of fermented and nonfermented dairy products: effects on cholesterol concentrations and metabolism. Am J Clin Nutr, 71, 674-681.
37. Toklu HZ, Hakan T, Celik H, et al (2010): Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats. J Spinal Cord Med, 33, 401-409.
38. Yu S, Yao S, Wen Y, et al (2016): Angiogenic microspheres promote neural regeneration and motor function recovery after spinal cord injury in rats. Sci Rep, 6, 1-13.
39. Zhang D, Ma G, Hou M, et al (2016): The neuroprotective effect of puerarin in acute spinal cord injury rats. Cell Physiol Biochem, 39, 1152-1164.
40. Zhang Z, Krebs CJ, Guth L (1997): Experimental analysis of progressive necrosis after spinal cord trauma in the rat: etiological role of the inflammatory response. Exp Neurol, 143, 141-152.