Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperTopiramate promotes neurological recovery in a new model of traumatic brain injury in rats
Highlights
▶Neuroprotective properties of topiramate in a traumatic brain injury model in rats. ▶Topiramate promotes neurological recovery in injured rats. ▶Topiramate exerts no effect on traumatic lesion volume. ▶Topiramate might play a role in reduction of brain edema. ▶There is no difference in outcome between the 40 and 60 mg/kg doses.
Section snippets
Experimental procedures
The study took place in the animal facilities of the Center for Experimental Surgery of the Biomedical Research Foundation of the Academy of Athens. The facilities are properly approved by the Veterinary Authority of the Prefect of Athens, in accordance with the provisions of the Presidential Decree 160/91 on the protection of animals used for experimental and other scientific purposes in compliance with Directive 86/609 of the European Union. The unit is also implementing a health surveillance
Study I—first part (neurological evaluation)
The groups that were treated with topiramate (groups B and C) presented substantially better clinical scores compared with the control group (group A) throughout the course of the study (Fig. 2). The differences became statistically significant in the tests that were performed 10 (P<0.05) and 20 (P<0.001) days after the injury (Table 1). All the animals had clinical improvement over time, but the rate of improvement was significantly faster for groups B and C. The animals that received the
Discussion
The serious socioeconomic consequences of brain injury in conjunction with the progress in the understanding of the traumatic brain injury pathophysiology, provoked great interest for the development of neuroprotective techniques and neuroprotective substances. However, the initial enthusiasm from the encouraging results of pre-clinical experimental studies was subsequently tempered by the negative results obtained in clinical studies. While there were more than 475 clinical studies concerning
Acknowledgments
We would like to thank the personnel of Janssen-Cilag Pharmaceutical SACI, Greece for assisting us with the required procedures regarding the provision of 5 g of topiramate powder that were used in the study. There are no personal or financial circumstances that constitute a conflict of interest.
References (41)
- et al.
Topiramate protects against glutamate- and kainate-induced neurotoxicity in primary neuronal-astroglial cultures
Epilepsy Res
(2003) - et al.
Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration
Life Sci
(2001) - et al.
Amelioration of water maze performance deficits by topiramate applied during pilocarpine-induced status epilepticus is negatively dose-dependent
Epilepsy Res
(2007) - et al.
Protective effect of topiramate against hippocampal neuronal damage after global ischemia in the gerbils
Neurosci Lett
(2000) - et al.
Anti-epileptic drugs as possible neuroprotectants in cerebral ischemia
Brain Res Brain Res Rev
(2003) - et al.
Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model
Neuroscience
(1989) - et al.
Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats
Exp Neurol
(2006) - et al.
Effects of the NMDA antagonist CP-98,113 on regional cerebral edema and cardiovascular, cognitive, and neurobehavioral function following experimental brain injury in the rat
Brain Res
(1998) - et al.
Neuroprotective effects of topiramate after hypoxia-ischemia in newborn piglets
Brain Res
(2005) - et al.
Topiramate prevents excitotoxic damage in the newborn rodent brain
Neurobiol Dis
(2005)
Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat
Brain Res
Critical appraisal of neuroprotection trials in head injury: what have we learned?
NeuroRx
Enhanced neuroprotection and reduced hemorrhagic incidence in focal cerebral ischemia of rat by low dose combination therapy of urokinase and topiramate
Neuropharmacology
Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization
Brain Res
Evaluation of topiramate neuroprotective effect in severe TBI using microdialysis
Ann N Y Acad Sci
Current status of neuroprotection trials for traumatic brain injury: lessons from animal models and clinical studies
Neurosurgery
Attenuation of brain edema, blood-brain barrier breakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-d-aspartate receptor antagonist, after experimental traumatic brain injury in rats
Neurosurgery
Neuroprotection and traumatic brain injury: theoretical option or realistic proposition
Curr Opin Neurol
Neuroprotection: challenges and opportunities
Arch Neurol
The effect of cyclosporin A on brain edema formation following experimental cortical contusion
Acta Neurochir Suppl
Cited by (0)
- 1
Present address: Department of Neurosurgery, Athens Naval and Veterans Hospital, Athens, Greece.
- 2
Present address: Department of Neurosurgery, Nicosia General Hospital, Nicosia, Cyprus.