Neuroprotective, Neuroplastic, and Neurobehavioral Effects of Daily Treatment With Levetiracetam in Experimental Traumatic Brain Injury

Zou, Huichao; Brayer, Samuel W.; Hurwitz, Maxwell; Niyonkuru, Christian; Fowler, Lorraine E.; Wagner, Amy K.

doi:10.1177/1545968313491007

Cited by 77 publications

(55 citation statements)

References 44 publications

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“…To offer more detail, LEV has recently been shown to be neuroprotective in a rodent model of controlled cortical impact (CCI) and subarachnoid hemorrhage (effect that has not been observed with PHT); administration of LEV but not PHT improved functional outcomes 34. Another rodent study showed that 20 days of LEV treatment following CCI, when compared with placebo, promoted neuronal sparing, decreased the volume of injury, and reduced release of pro-inflammatory interleukin (IL)-1β 35. Finally, LEV alone or in combination with diazepam decreased seizure-related hippocampal neurodegeneration 36.…”

Section: Seizure and Epilepsy Prevention After Tbimentioning

confidence: 99%

“…Animal studies indicate that brain trauma causes global, in addition to focal, abnormalities, and that these abnormalities are most pronounced in the most vulnerable areas – ie, hippocampus 49. Further, animal model research has documented the relationship between TBI and seizures50–52 and the positive impact of seizure medication treatments on improving neurobehavioral outcomes in TBI 35,53. Recently, human studies have shown that seizures in patients with TBI disproportionately contribute to hippocampal atrophy,54 that seizures cause increases in intracranial pressure and increased lactate/pyruvate ratio, both of which have deleterious effects on post-TBI recovery,55,56 and that patients with seizures related to any type of brain injury, when compared with matched patients without injury, have poorer outcomes and higher mortality 57–60.…”

Section: Seizure and Epilepsy Prevention After Tbimentioning

confidence: 99%

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Post-traumatic epilepsy: current and emerging treatment options

Szaflarski¹,

Nazzal²,

Dreer³

2014

NDT

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Traumatic brain injury (TBI) leads to many undesired problems and complications, including immediate and long-term seizures/epilepsy, changes in mood, behavioral, and personality problems, cognitive and motor deficits, movement disorders, and sleep problems. Clinicians involved in the treatment of patients with acute TBI need to be aware of a number of issues, including the incidence and prevalence of early seizures and post-traumatic epilepsy (PTE), comorbidities associated with seizures and anticonvulsant therapies, and factors that can contribute to their emergence. While strong scientific evidence for early seizure prevention in TBI is available for phenytoin (PHT), other antiepileptic medications, eg, levetiracetam (LEV), are also being utilized in clinical settings. The use of PHT has its drawbacks, including cognitive side effects and effects on function recovery. Rates of recovery after TBI are expected to plateau after a certain period of time. Nevertheless, some patients continue to improve while others deteriorate without any clear contributing factors. Thus, one must ask, ‘Are there any actions that can be taken to decrease the chance of post-traumatic seizures and epilepsy while minimizing potential short- and long-term effects of anticonvulsants?’ While the answer is ‘probably,’ more evidence is needed to replace PHT with LEV on a permanent basis. Some have proposed studies to address this issue, while others look toward different options, including other anticonvulsants (eg, perampanel or other AMPA antagonists), or less established treatments (eg, ketamine). In this review, we focus on a comparison of the use of PHT versus LEV in the acute TBI setting and summarize the clinical aspects of seizure prevention in humans with appropriate, but general, references to the animal literature.

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Section: Seizure and Epilepsy Prevention After Tbimentioning

confidence: 99%

Section: Seizure and Epilepsy Prevention After Tbimentioning

confidence: 99%

Post-traumatic epilepsy: current and emerging treatment options

Szaflarski¹,

Nazzal²,

Dreer³

2014

NDT

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“…LEV was found to act through the inhibition of the synaptic vesicle protein 2A [43], but also the inhibition of HVA-Ca 2+ channels (N-type). Moreover, it can negate the inhibition of negative allosteric modulators, such as zinc and β-carbolines of γ-aminobutyric acid (GABA)-and glycine-gated currents, and diminish the calcium release from intraneuronal stores [43,44].…”

Section: Discussionmentioning

confidence: 99%

“…SV2A appears to be important for the availability of calcium dependent neurotransmitter vesicles ready to release their content [8]. Numerous studies have suggested that levetiracetam has considerable neuroprotective properties in both epileptic and nonepileptic disorders [9][10][11][12][13]. Its neuroprotection was demonstrated in several brain injury as well as neurodegenerative disease prototypes.…”

Section: Introductionmentioning

confidence: 99%

Increased neurogenesis after ACEA and levetiracetam treatment in mouse pilocarpine model of epilepsy

Zagaja¹,

Szewczyk²,

Haratym-Maj³

et al. 2017

J Pre Clin Clin Res.

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Introduction and objectives. The aim of the study was to asses the impact of long-term therapy with the second generation antiepileptic drug levetiracetam (LEV) with arachidonyl-2'-chloroethylamide (ACEA), a highly selective cannabinoid CB1 receptor agoniston the process of neurogenesis in a mouse pilocarpine model of epilepsy (PILO). Additionally, a relationship was established between the treatment with ACEA in combination with LEV, and hippocampal neurogenesis in mouse PILO brain. Materials and method. All experiments were performed on adolescent male CB57/BL mice injected i.p. with LEV (10 mg/kg), ACEA (10 mg/kg) and PMSF (30 mg/kg) (phenylmethylsulfonyl fluoride -a substance protecting ACEA against degradation by the fatty-acid amidohydrolase), pilocarpine (PILO, a single dose 290 mg/kg) and methylscopolamine (30 min before PILO to stop the peripheral cholinergic effects of the pilocarpine, 1 mg/kg). The process of neurogenesis was evaluated after10 days treatment with LEV and ACEA. Results. Obtained results indicated that the combinations of ACEA+PMSF+LEV and ACEA +PMSF increased the total number of total newborn cells compared to the control. Moreover, ACEA+PMSF administered alone and in combination with LEV had a significant impact on neurogenesis increasing the total number of newborn neurons compared to the control group. Neither LEV nor PMSF had a significant impact on the number of proliferating cells and newborn neurons when compared to the control PILO group. In turn, LEV administered alone decreased significantly the number of astrocytes. However, ACEA+PMSF has demonstrated significant increase of astrocytes compare to control mice. Conclusions. These data provide substantial evidence that the combination of LEV+ACEA significantly increases the level of newborn neurons in the PILO dentate subgranular zone.

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“…It has shown a high affinity for synaptic vesicle protein 2A, a molecule involved in the release of neurotransmitters [35]. Zou et al [36] suggested that daily LEV treatment has beneficial effects on improvement of neurological recovery after TBI, via modulation of neuroinflammatory and excitatory pathways. Moreover, its dosage is between 1000-3000 mg, with a half-life between 6-8 hours, with minimal drug-drug interactions [37].…”

Section: Sensitivity Analysis and Publication Biasmentioning

confidence: 99%

The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: A systematic review and meta-analysis

Xu¹,

Shen²,

Shao

et al. 2016

Brain Injury

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Neuroprotective, Neuroplastic, and Neurobehavioral Effects of Daily Treatment With Levetiracetam in Experimental Traumatic Brain Injury

Abstract: These results suggest that daily LEV treatment has beneficial effects on histological, molecular, and behavioral elements of neurological recovery after TBI, in part, via modulation of neuroinflammatory and excitatory pathways.

Cited by 77 publications

References 44 publications

Post-traumatic epilepsy: current and emerging treatment options

Post-traumatic epilepsy: current and emerging treatment options

Increased neurogenesis after ACEA and levetiracetam treatment in mouse pilocarpine model of epilepsy

The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: A systematic review and meta-analysis

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