Therapeutic effects of eugenol in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study

10.1016/j.jtcme.2021.01.003

Jeetprakash Barot；Bhagawati Saxena

Traumatic brain injury ； Eugenol ； Blood-brain barrier permeability ； Brain edema ； Neuroprotection

Journal of Traditional and Complementary Medicine

11卷4期（2021 / 07 / 01）

318 - 327

英文

Background and aim: Traumatic brain injury (TBI) results in death or long term functional disabilities. Eugenol is demonstrated to be beneficial in a range of experimental models of neurological disorders via its anti-inflammatory and antioxidant properties. Thus, the present study was designed to investigate the neuroprotective effects of eugenol in a weight-drop induced rat model of TBI. Experimental procedure: Rats were assigned into five groups; control and TBI groups pretreated with vehicle, and three TBI groups pretreated with different doses of eugenol (25, 50, and 100 mg/kg/day, p.o., seven consecutive days). Except for the control, all other groups were subjected to TBI using Marmarou's weight-drop method. 24 h after TBI, locomotor functions and short term memory were evaluated. Lastly animals were scarified and the estimation of lipid peroxidation in brain tissue, blood-brain barrier (BBB) integrity, brain water content (brain edema) and histopathology of the brain tissue were performed. Results: Weight-drop induced TBI caused functional disabilities in the rats as indicated by impairment in locomotor activities and short term memory. The TBI also resulted in augmented neuronal cell death designated by chromatolysis. The results also showed disruption in the BBB integrity, increased edema, and lipid peroxidation in the brain of the rats exposed to trauma. Pretreatment with eugenol (100 mg/kg) ameliorated histopathological, neurochemical, and behavioral consequences of trauma. Conclusion: For the first time this study revealed that eugenol can be considered as a potential candidate for managing the functional disabilities associated with TBI because of its antioxidant activities.

1. Bor-Seng-Shu, E,Figueiredo, EG,Fonoff, ET,Fujimoto, Y,Panerai, RB,Teixeira, MJ(2013).Decompressive craniectomy and head injury: brain morphometry, ICP, cerebral hemodynamics, cerebral microvascular reactivity, and neurochemistry.Neurosurg Rev,36(3),361-370.
2. Capizzi, A,Woo, J,Verduzco-Gutierrez, M(2020).Traumatic brain injury: an overview of epidemiology, pathophysiology, and medical management.Med Clin,104(2),213-238.
3. Chavali, VD,Agarwal, M,Vyas, VK,Saxena, B(2020).Neuroprotective effects of ethyl pyruvate against aluminum chloride-induced Alzheimer’s disease in rats via inhibiting toll-like receptor 4.J Mol Neurosci.,70(6),836-850.
4. Chiu, CC,Liao, YE,Yang, LY(2016).Neuroinflammation in animal models of traumatic brain injury.J Neurosci Methods,272,38-49.
5. Cole, JT,Yarnell, A,Kean, WS(2011).Craniotomy: true sham for traumatic brain injury, or a sham of a sham?.J Neurotrauma,28(3),359-369.
6. Dellu, F,Mayo, W,Cherkaoui, J,Le Moal, M,Simon, H(1992).A two-trial memory task with automated recording: study in young and aged rats.Brain Res,588(1),132-139.
7. Deselms, H,Maggio, N,Rubovitch, V(2016).Novel pharmaceutical treatments for minimal traumatic brain injury and evaluation of animal models and methodologies supporting their development.J Neurosci Methods.,272,69-76.
8. DEWS, PB(1953).The measurement of the influence of drugs on voluntary activity in mice.Br J Pharmacol Chemother,8(1),46-48.
9. Draper, HH,Hadley, M(1990).Malondialdehyde determination as index of lipid peroxidation.Methods Enzymol,186,421-431.
10. Farooqui, AA,Horrocks, LA(1998).Lipid peroxides in the free radical pathophysiology of brain diseases.Cell Mol Neurobiol,18(6),599-608.
11. Garabadu, D,Shah, A,Ahmad, A(2011).Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress.Stress,14(2),145-155.
12. Garabadu, D,Sharma, M(2019).Eugenol attenuates scopolamine-induced hippocampal cholinergic, glutamatergic, and mitochondrial toxicity in experimental rats.Neurotox Res,35(4),848-859.
13. Goldstein, LB(2003).Model of recovery of locomotor ability after sensorimotor cortex injury in rats.ILAR J.,44(2),125-129.
14. Goldstein, LB,Davis, JN(1990).Beam-walking in rats: studies towards developing an animal model of functional recovery after brain injury.J Neurosci Methods,31(2),101-107.
15. Greve, MW,Zink, BJ(2009).Pathophysiology of traumatic brain injury.Mt Sinai J Med.,76(2),97-104.
16. Hamm, RJ,Pike, BR,O’Dell, DM,Lyeth, BG,Jenkins, LW(1994).The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.J Neurotrauma,11(2),187-196.
17. Honeybul, S(2017).Decompressive craniectomy for severe traumatic brain injury reduces mortality but increases survival with severe disability.Evid Base Med,22(2),61.
18. Hou, J,Nelson, R,Wilkie, Z(2017).Mild and mild-to-moderate traumatic brain injury-induced significant progressive and enduring multiple comorbidities.J Neurotrauma,34(16),2456-2466.
19. Ikeda, Y,Long, DM(1990).The molecular basis of brain injury and brain edema: the role of oxygen free radicals.Neurosurgery,27(1),1-11.
20. Júnior, PL,Câmara, DA,Costa, AS(2016).Apoptotic effect of eugenol involves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect on cancer cell in vitro.Phytomedicine,23(7),725-735.
21. Kabuto, H,Tada, M,Kohno, M(2007).Eugenol [2-methoxy-4-(2-propenyl)phenol] prevents 6-hydroxydopamine-induced dopamine depression and lipid perox-idation inductivity in mouse striatum.Biol Pharm Bull.,30(3),423-427.
22. Katayama, S,Shionoya, H,Ohtake, S(1978).A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in Guinea pigs and rats.Microbiol Immunol,22(2),89-101.
23. Kline, AE,Massucci, JL,Ma, X,Zafonte, RD,Dixon, CE(2004).Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma.J Neurotrauma,21(12),1712-1722.
24. Lad, KA,Maheshwari, A,Saxena, B(2019).Repositioning of an anti-depressant drug, agomelatine as therapy for brain injury induced by craniotomy.Drug Discov Ther,13(4),189-197.
25. Ma, L,Mu, Y,Zhang, Z,Sun, Q(2018).Eugenol promotes functional recovery and alleviates inflammation, oxidative stress, and neural apoptosis in a rat model of spinal cord injury.Restor Neurol Neurosci,36(5),659-668.
26. Maier NRF. The cortical area concerned with coordinated walking in the rat. J Comp Neurol. 1935;61(2):5-395. https://doi.org/10.1002/cne.900610209
27. Manaenko, A,Chen, H,Kammer, J,Zhang, JH,Tang, J(2011).Comparison Evans Blue injection routes: intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model.J Neurosci Methods,195(2),206-210.
28. Manikandan, P,Vinothini, G,Vidya Priyadarsini, R,Prathiba, D,Nagini, S(2011).Eugenol inhibits cell proliferation via NF-kB suppression in a rat model of gastric carcinogenesis induced by MNNG.Invest N Drugs,29(1),110-117.
29. Marmarou, A,Foda, MA,van den Brink, W,Campbell, J,Kita, H,Demetriadou, K(1994).A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics.J Neurosurg,80(2),291-300.
30. Menon, DK,Schwab, K,Wright, DW,Maas, AI(2010).Demographics and clinical assessment working group of the international and interagency initiative toward common data elements for Research on traumatic brain injury and psychological health. Position statement: definition of traumatic brain injury.Arch Phys Med Rehabil,91(11),1637-1640.
31. Mesole, SB,Alfred, OO,Yusuf, UA,Lukubi, L,Ndhlovu, D(2020).Apoptotic inducement of neuronal cells by aluminium chloride and the neuroprotective effect of eugenol in wistar rats.Oxid Med Cell Longev,2020,8425643.
32. Miotto, EC,Cinalli, FZ,Serrao, VT,Benute, GG,Lucia, MC,Scaff, M(2010).Cognitive deficits in patients with mild to moderate traumatic brain injury.Arq Neuropsiquiatr,68(6),862-868.
33. Mustafa, AG,Alshboul, OA(2013).Pathophysiology of traumatic brain injury.Neurosciences,18(3),222-234.
34. Namjoshi, DR,Good, C,Cheng, WH(2013).Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biome-chanical perspective.Dis Model Mech,6(6),1325-1338.
35. Narayan, RK,Michel, ME,Ansell, B(2002).Clinical trials in head injury.J Neurotrauma,19(5),503-557.
36. National Toxicology Program(1983).Carcinogenesis studies of eugenol (CAS No. 97-53-0) in F344/N rats and B6C3F1 mice (feed studies).Natl Toxicol Progr Tech Rep,223,1-159.
37. Pezzoli, M,Elhamdani, A,Camacho, S(2014).Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices.Sci Rep.,4,6825.
38. Prasad, SN,Muralidhara(2013).Neuroprotective efficacy of eugenol and isoeugenol in acrylamide-induced neuropathy in rats: behavioral and biochemical evidence.Neurochem Res,38(2),330-345.
39. Said, MM(2011).The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney.Fundam Clin Pharmacol,25(6),708-716.
40. Said, MM,Rabo, MM(2017).Neuroprotective effects of eugenol against aluminium induced toxicity in the rat brain.Arh Hig Rada Toksikol,68(1),27-37.
41. Schallert, T,Fleming, SM,Leasure, JL,Tillerson, JL,Bland, ST(2000).CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury.Neuropharmacology,39(5),777-787.
42. Shigeno, T,Brock, M,Shigeno, S,Fritschka, E,Cervós-Navarro, J(1982).The determination of brain water content: microgravimetry versus drying-weighing method.J Neurosurg,57(1),99-107.
43. Shlosberg, D,Benifla, M,Kaufer, D,Friedman, A(2010).Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury.Nat Rev Neurol,6(7),393-403.
44. Singh, V,Panwar, R.(2014).In vivo antioxidative and neuroprotective effect of 4-Allyl-2-methoxyphenol against chlorpyrifos-induced neurotoxicity in rat brain.Mol Cell Biochem,388(1-2),61-74.
45. Vincent, AS,Roebuck-Spencer, TM,Cernich, A(2014).Cognitive changes and dementia risk after traumatic brain injury: implications for aging military personnel.Alzheimers Dement,10(3 Suppl),S174-S187.
46. Walker, WC,Pickett, TC(2007).Motor impairment after severe traumatic brain injury: a longitudinal multicenter study.J Rehabil Res Dev.,44(7),975-982.
47. Werner, C,Engelhard, K(2007).Pathophysiology of traumatic brain injury.Br J Anaesth,99(1),4-9.
48. Won, MH,Lee, JC,Kim, YH(1998).Postischemic hypothermia induced by eugenol protects hippocampal neurons from global ischemia in gerbils.Neurosci Lett,254(2),101-104.
49. Xiong, Y,Mahmood, A,Chopp, M.(2013).Animal models of traumatic brain injury.Nat Rev Neurosci,14(2),128-142.
50. Zhang, LL,Zhang, LF,Xu, JG,Hu, QP(2017).Comparison study on antioxidant, DNA damage protective and antibacterial activities of eugenol and isoeugenol against several foodborne pathogens.Food Nutr Res.,61(1),1353356.