Effects of atorvastatin on experimental spinal cord ischemia-reperfusion injury in rabbits

Abstract

ABSTRACT(ROS), and lipid peroxidation (43). Studies have demonstrated increased glutamate release, activation of glutamate receptors and accumulation of calcium result in increased glutamate (3,21).Statins are a group of drugs that competitively inhibit the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the first enzyme of the HMG-CoA reductase pathway. This inhibition impedes production of mevalonate, the next molecule in the cascade producing cholesterol. This action ultimately █ INTRODUCTION S pinal cord injury (SCI) is a mechanical insult followed by a secondary cascade of biologic events promoting permanent tissue damage. Excitotoxicity, oxidative stress and inflammatory response are the mediators of secondary injury, which is -theoretically-preventable (5,16). In the central nervous system (CNS), ischemic traumatic injury, cell loss and neuronal dysfunction, is thought to be the result of glutamatemediated excitotoxicity, formation of reactive oxygen species AIm: Extent of secondary injury is the determinant of tissue destruction and functional worsening after primary spinal cord injury (SCI). Data have accumulated on alleviation of secondary injury in SCI from many studies on the subject. Besides its cholesterol lowering effects, statins are known to have anti-inflammatory and anti-oxidant effects which are the main targets of spinal cord research. This study aims to evaluate the effects of atorvastatin on experimental spinal cord ischemia-reperfusion injury. mATERIAl and mEThODS: Thirty adult male New Zealand rabbits were allocated into control, ischemia-reperfusion (I/R) and treatment groups. Treatment group received 5 mg/kg of atorvastatin via lavage for the preceding 14 days. Other groups received placebo during the same time period. After two weeks, animals in the I/R and treatment groups underwent abdominal temporary aorta occlusion for 30 minutes. Neurological condition of the animals was recorded during the 48 hours of observation. Afterwards, animals were sacrificed and levels of malondialdehyde, glutathione and nitric oxide in spinal cord tissue and plasma and the histopathological tissue changes were determined. RESUlTS:Animals in the treatment groups demonstrated significantly better results than the I/R group regarding biochemical markers. Neurological evaluation using the Tarlov scale demonstrated significantly better results at the 48 th hour in treatment group. Histopathological results were also better in the treatment groups. CONClUSION:Results of this study demonstrate the neuroprotective effects of atorvastatin. Atorvastatin has favorable effects on biochemical markers of oxidative stress in SCI. Further studies with larger cohorts and different time periods are also needed.

Potential immunotherapies for traumatic brain and spinal cord injury

“…Among statins, atorvastatin exhibits neuroprotective effect in many preclinical studies on both TBI 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 and SCI. 155 , 156 , 157 , 158 Although many mechanisms may contribute to atorvastatin's neuroprotective effects, the microglia/macrophage polarization may play a more predominant role. 159 Acute atorvastatin administration in mice with TBI effectively reduced inflammatory responses by suppressing microglia/macrophage activation and immune cell invasion.…”

Pathophysiology and Therapeutic Approaches for Spinal Cord Injury

“…In acute SCI context, atorvastatin was evaluated in a 5 mg/kg dosage administered via oral gavage [148] and by intraperitoneal injection [149]. Atorvastatin revealed neuroprotective effects by decreasing biochemical markers of oxidative stress, mild glial cell infiltration, p53, and MMP-9, increasing spare axons [150], and upregulating MBP levels [151]. In addition, Haazza and colleagues also found atorvastatin to improve hindlimb function, sensory response to noxious stimuli, and placing/stepping reflex in a model of ischemia-reperfusion injury of the spinal cord.…”

Effects of Lipoic Acid on Ischemia‐Reperfusion Injury

“…Spinal I/R injury further induces nerve injuries and damages of sensation and movement (even paraplegia) [ 110 ]. Oxidative stress, inflammation, and excitotoxicity were considered playing vital roles in spinal I/R injury [ 111 ]. In previous studies, some therapeutic measures had been used to cure spinal I/R injury (e.g., the preconditionings of hyperbaric oxygen [ 112 ] and remote ischemia [ 113 ], pharmacologic administrations such as progesterone [ 114 ], and the application of pluripotent stem cells [ 115 ]), but the effects of treatments were yet unsatisfied.…”