Neuroprotective effects of mildronate in a rat model of traumatic brain injury. Issue 10 (October 2019)

• Record Type: Journal Article
• Authors: Demir, Dilan; Kuru Bektaşoğlu, Pınar; Koyuncuoğlu, Türkan; Kandemir, Cansu; Akakın, Dilek; Yüksel, Meral; Çelikoğlu, Erhan; Yeğen, Berrak Ç.; Gürer, Bora
• Is Part Of: Injury. Volume 50:Issue 10(2019)
• Page Start: 1586
• Page End: 1592
• Publication Date: 2019-10
• Subjects: Antiapoptotic effect -- Diffuse brain injury -- Mildronate -- Neuroprotection; Wounds and injuries -- Surgery -- Periodicals; Accidents -- Periodicals; Wounds and Injuries -- surgery -- Periodicals; Lésions et blessures -- Chirurgie -- Périodiques; Electronic journals; Electronic journals; 617.1
• DOI: 10.1016/j.injury.2019.08.036
• Languages: English
• ISSNs: 0020-1383

Abstract

Highlights: Traumatic brain injury causes oxidative stress, inflammation and apoptosis in the brain tissue. Mildronate exerts anti-inflammatory, antiapoptotic and antioxidant effects. In this study, for the first time, neuroprotective effects of mildronate in traumatic brain injury have been documented. Abstract: Objective: Traumatic brain injury (TBI) is one of the most common preventable causes of mortality and morbidity. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophysiological mechanisms underlying neuronal loss after TBI. Mildronate is demonstrated to be beneficial in various experimental models of ischemic diseases via anti-inflammatory, antioxidant, and neuroprotective mechanisms. This study aimed to investigate possible antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of mildronate in a rat model of TBI. Methods: A total of 46 male rats were divided into three groups of control, saline-treated TBI, and mildronate-treated TBI. Both TBI groups were subjected to closed-head contusive weight-drop injuries followed by treatment with saline or mildronate (100 mg/kg) administered intraperitoneally. The forebrain was removed 24 h after trauma induction, the activities of myeloperoxidase (MPO) and caspase-3, levels of superoxide dismutase (SOD), luminol- and lucigenin-enhanced chemiluminescence were measured, and histomorphological evaluation of cerebral tissues was performed. Results: Increased MPO and caspase-3 activities in the vehicle-treated TBI group (p < 0.001) were suppressed in the mildronate-treated TBI group (p < 0.001). Similarly, increase in luminol and lucigenin levels (p < 0.001 and p < 0.01, respectively) in the vehicle-treated TBI group were decreased in the mildronate-treated TBI group (p < 0.001). Concomitantly, in the vehicle-treated TBI group, TBI-induced decrease in SOD activity (p < 0.01) was reversed with mildronate treatment (p < 0.05). On histopathological examination, TBI-induced damage in the cerebral cortex was lesser in the mildronate-treated TBI group than that in other groups. Conclusion: This study revealed for the first time that mildronate, exhibits neuroprotective effects against TBI because of its anti-inflammatory, antiapoptotic, and antioxidant activities.