Ultrastructure protection and attenuation of lipid peroxidation after blockade of presynaptic release of glutamate by lamotrigine in experimental spinal cord injury

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>Lamotrigine is an antiepileptic drug that inhibits presynaptic voltage-gated sodium channels and reduces the presynaptic release of glutamate in pathological states. Neuroprotective effects of this drug have already been demonstrated in cerebral ischemia models. The aim of the present study was to determine the effects of presynaptic glutamate release inhibition on experimental spinal cord injury (SCI).</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A total of 66 adult Wistar rats were randomly allocated into 6 groups. Group I was the control group used to obtain normal blood samples and spinal cord specimens. Spinal cord injury was introduced by using the extradural clip compression technique, but no medication was given to Group II (trauma group) rats. Group III was treated with vehicle, and the same amount of dimethyl sulfoxide used in treatment groups was administered to these rats. A dose of 50 mg/kg lamotrigine was administered intraperitoneally to Group IV (pretreatment), Group V (peritreatment), and Group VI (posttreatment) rats 30 minutes before, during, and 30 minutes after SCI, respectively. Oxidative stress parameters and transmission electron microscopic findings were examined.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Blockade of presynaptic release of glutamate by lamotrigine treatment yielded protective effects on the spinal cord ultrastructure even when administered after the SCI, but it prevented oxidative stress only when it was administered before or during the SCI.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Currently, no available agent has been identified, that can block all the glutamate receptors at the same time. To prevent excitotoxicity in SCI, inhibiting glutamate release from the presynaptic buttons instead of blocking the postsynaptic glutamate receptors seems to be a more rational approach. Further research, such as neurobehavioral assessment, is warranted to demonstrate the probable neuroprotective effects of presynaptic glutamate release inhibition in SCI.</jats:p></jats:sec>

Neuroprotective effects of lacosamide in experimental traumatic spinal cord injury in rats

“…In humans, SCI is most commonly caused by a combination of acute impact and persistent compression and shows two consecutive stages (5). First, the vertebral fracture fragments Several studies have investigated pharmacologic agents that were presumed to have neuroprotective effects after SCI, but only methylprednisolone has shown beneficial effects in large clinical studies (13-15, 30,31,33). Although it has beneficial effects on parenchymal damage, there is no significant improvement of functional recovery (25).…”

Possible Effects of Lamotrigine on Liver of Wister Rats Exposed to Chemoconvulsion and Chronic Restraint Model

“…Although the anti-oxidant effect of LTG in an experimental model of spinal cord injury (15), however, hepatic reactions to LTG ranged from transient elevation of hepatic enzymes without clinical signs or symptoms of hepatic dysfunctions to fatal hepatotoxicity . In the light of potential toxicity, clinicians prescribing LTG as a single therapy or polytherapy must have attention to the possibility of occurance of an autoimmune LTG-induced hepatitis up to reaching many serious hepatic reactions particularly in case of polytherapy with enzyme inducing drugs as carbamazepine, keeping in mind that many antiepileptic drugs, possess an apparent anti-oxidant effect on different body organs e.g.…”

Lamotrigine, a mood stabilizer, may have beneficial effects on memory acquisition and retrieval in mice

“…It has been previously reported that possible GABAergic mechanism has a role in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity (Kumar et al, 2012). Neuroprotective effects of LMG have been demonstrated in cerebral ischemia models (Tufan et al, 2008). Lamotrigine acts as a mood stabilizer by inhibiting excessive glutamate release but NMDA receptor-mediated glutamate transmission is important in the formation of long term potentiation and learning and memory.…”