CC BY-NC-ND 4.0 · Indian Journal of Neurotrauma 2022; 19(02): 100-104
DOI: 10.1055/s-0041-1724148
Original Article

Neuroprotective Effects of Sildenafil on Traumatic Brain Injury in an Experimental Rat Model

Serdar Ercan
1   Department of Neurosurgery, Eskisehir City Hospital, Eskisehir, Turkey
,
Ayfer Aktaş
2   Dicle University, Medical Faculty, Department of Histology & Embryology, Diyarbakir, Diyarbakir, Turkey
› Author Affiliations
Funding None.

Abstract

Objective Not only primary injuries, secondary injuries such as posttraumatic biochemical cascades, ischemia, and hypoxia also affect the morbidity and mortality of traumatic brain injury (TBI). Sildenafil released the vasodilatation by relaxing the smooth muscle of the systemic artery and vein. Also, the effects of sildenafil are evidenced in multiple sclerosis, Alzheimer's disease, and memory loss as a part of experimental studies. Sildenafil decreases oxidative stress by increasing the cGMP level. We aimed to examine the protective effects of sildenafil on TBI with histopathological and biochemical parameters.

Method 21 Sprague–Dawley rats were separated into three groups (n = 7). “The weight drop injury model,” which was described by Marmou, was used for the head injury. Group 1: nontraumatic sham group, Group 2: nontreated TBI group, Group 3: sildenafil (100 mg/kg) treated TBI group. The whole brain and serum were collected for histopathological and biochemical study. The histopathological sections were examined under a light microscope.

Results On comparison of total antioxidant status (TAS), total oxidant status (TOS), nitric oxide (NO), and plasma nitrite/nitrate (PNOx) between groups, NO level was significantly high in group 3 (p = 0.013). Even though the TAS level was significantly high in group 3 (p = 0.02), there were no significant differences in TOS level in groups (p = 0.225). Disappearing Nissle granules occurred in a pyknotic situation in the cell nucleus, and acidophilic staining in neuron cells, which describe the neuron degeneration observed in the trauma group. The neuron degeneration markers were not seen in the sildenafil-treated trauma group.

Conclusion Our study has shown that sildenafil decreases the oxygen radicals and affects the recovery of experimental TBI in rats.



Publication History

Article published online:
18 February 2021

© 2021. Neurotrauma Society of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J Head Trauma Rehabil 2010; 25 (02) 72-80
  • 2 Bruns Jr J, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia 2003; 44 (s10) 2-10
  • 3 Kraus JF, McArthur DL. Epidemiologic aspects of brain injury. Neurol Clin 1996; 14 (02) 435-450
  • 4 Langlois JA, Rutland-Brown W, Thomas KE. The incidence of traumatic brain injury among children in the United States: differences by race. J Head Trauma Rehabil 2005; 20 (03) 229-238
  • 5 Chesnut RM, Marshall LF, Klauber MR. et al The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993; 34 (02) 216-222
  • 6 Ozsüer H, Görgülü A, Kiriş T, Cobanoğlu S. The effects of memantine on lipid peroxidation following closed-head trauma in rats. Neurosurg Rev 2005; 28 (02) 143-147
  • 7 Kayali H, Ozdag MF, Kahraman S. et al The antioxidant effect ofβ-Glucan on oxidative stress status in experimental spinal cord injury in rats. Neurosurg Rev 2005; 28 (04) 298-302
  • 8 Marmarou A, Signoretti S, Fatouros PP, Portella G, Aygok GA, Bullock MR. Predominance of cellular edema in traumatic brain swelling in patients with severe head injuries. J Neurosurg 2006; 104 (05) 720-730
  • 9 Hatton J. Pharmacological treatment of traumatic brain injury: a review of agents in development. CNS Drugs 2001; 15 (07) 553-581
  • 10 Hall ED, Vaishnav RA, Mustafa AG. Antioxidant therapies for traumatic brain injury. Neurotherapeutics 2010; 7 (01) 51-61
  • 11 Corbin JD, Francis SH. Cyclic GMP phosphodiesterase-5: target of sildenafil. J Biol Chem 1999; 274 (20) 13729-13732
  • 12 Chen J, Li Y, Wang L. et al Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001; 32 (04) 1005-1011
  • 13 Uthayathas S, Karuppagounder SS, Tamer SI. et al Evaluation of neuroprotective and anti-fatigue effects of sildenafil. Life Sci 2007; 81 (12) 988-992
  • 14 Uthayathas S, Karuppagounder SS, Thrash BM, Parameshwaran K, Suppiramaniam V, Dhanasekaran M. Versatile effects of sildenafil: recent pharmacological applications. Pharmacol Rep 2007; 59 (02) 150-163
  • 15 Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 1994; 80 (02) 291-300
  • 16 Unterberg AW, Stover J, Kress B, Kiening KL. Edema and brain trauma. Neuroscience 2004; 129 (04) 1021-1029
  • 17 Cernak I, Chapman SM, Hamlin GP, Vink R. Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats. J Clin Neurosci 2002; 9 (05) 565-572
  • 18 Khan M, Sekhon B, Jatana M. et al Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res 2004; 76 (04) 519-527
  • 19 Zhang R, Wang Y, Zhang L. et al Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 2002; 33 (11) 2675-2680
  • 20 Farooq MU, Naravetla B, Moore PW, Majid A, Gupta R, Kassab MY. Role of sildenafil in neurological disorders. Clin Neuropharmacol 2008; 31 (06) 353-362
  • 21 Devan BD, Bowker JL, Duffy KB. et al Phosphodiesterase inhibition by sildenafil citrate attenuates a maze learning impairment in rats induced by nitric oxide synthase inhibition. Psychopharmacology (Berl) 2006; 183 (04) 439-445
  • 22 Zhang RL, Zhang Z, Zhang L, Wang Y, Zhang C, Chopp M. Delayed treatment with sildenafil enhances neurogenesis and improves functional recovery in aged rats after focal cerebral ischemia. J Neurosci Res 2006; 83 (07) 1213-1219
  • 23 Wang L, Gang Zhang Z, Lan Zhang R, Chopp M. Activation of the PI3-K/Akt pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricular zone. J Cereb Blood Flow Metab 2005; 25 (09) 1150-1158