Epilepsy Related to Traumatic Brain Injury

Pitkänen, Asla; Immonen, Riikka

doi:10.1007/s13311-014-0260-7

Cited by 132 publications

(94 citation statements)

References 98 publications

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“…More recent clinical trials, in which the development of epilepsy was the primary or secondary outcome measure investigated molecules with neuroprotective properties, in addition to newer AEDs (Pitkänen and Immonen 2014;Trinka and Brigo 2014). The first proofof-concept experimental AEG studies 15 years ago were also performed using standard AEDs, and treatments targeting the molecular and cellular mechanisms related to circuitry reorganization were introduced more recently (see Pitkänen and Kubova 2004;Pitkänen and Lukasiuk 2011).…”

Section: Antiepileptogenesis Proof-of-concept Studies In In Vivo Modelsmentioning

confidence: 99%

Epileptogenesis

Pitkänen

Łukasiuk²,

Dudek

et al. 2015

Cold Spring Harb Perspect Med

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173

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Epileptogenesis is a chronic process that can be triggered by genetic or acquired factors, and that can continue long after epilepsy diagnosis. In 2015, epileptogenesis is not a treatment indication, and there are no therapies available in clinic to treat individuals at risk of epileptogenesis. However, thanks to active research, a large number of animal models have become available for search of molecular mechanisms of epileptogenesis. The first glimpses of treatment targets and biomarkers that could be developed to become useful in clinic are in sight. However, the heterogeneity of the epilepsy condition, and the dynamics of molecular changes over the course of epileptogenesis remain as challenges to overcome.

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Section: Antiepileptogenesis Proof-of-concept Studies In In Vivo Modelsmentioning

confidence: 99%

Epileptogenesis

Pitkänen

Łukasiuk²,

Dudek

et al. 2015

Cold Spring Harb Perspect Med

Self Cite

275

173

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“…The incidence of emergency department visits due to TBI varies depending on patient age, with the highest incidences occurring in children aged 0-4 y (1,256 per 100,000 per year) and in older adolescents aged 15-19 y (757 per 100,000 per year) (2). TBI can result in a myriad of chronic comorbidities, including behavioral and cognitive impairment as well as epileptogenesis, which significantly compromise quality of life (3). In 2010, the estimated cost of TBI, including both direct and indirect medical costs, was approximately $76.5 billion in the United States and V33 billion in Europe (4,5).…”

mentioning

confidence: 99%

Ex Vivo Tracing of NMDA and GABA-A Receptors in Rat Brain After Traumatic Brain Injury Using ¹⁸F-GE-179 and ¹⁸F-GE-194 Autoradiography

et al. 2016

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In vivo imaging of N-methyl-D-aspartate (NMDA) glutamate receptor and γ-aminobutyric acid (GABA)-A receptor during progression of brain pathology is challenging because of the lack of imaging tracers with high affinity and specificity. Methods: We monitored changes in NMDA receptor and GABA-A receptor in a clinically relevant model of traumatic brain injury (TBI) induced by lateral fluid percussion in adult rats, using 2 new ligands for PET: 18 F-GE-179 for the open/active state of the NMDA receptor ion channel and 18 F-GE-194 for GABA-A receptor. Ex vivo brain autoradiography of radioligands was performed at subacute (5-6 d) and chronic (40-42 d) time points after TBI. Results: At 5-6 d after TBI, 18 F-GE-179 binding was higher in the cortical lesion area, in the lesion core, and in the hippocampus than in the corresponding contralateral regions; this increase was probably related to increased permeability of the blood-brain barrier. At 40-42 d after TBI, 18 F-GE-179 binding was significantly higher in the medial cortex, in the corpus callosum, and in the thalamus than in the corresponding contralateral regions. Five to 6 days after TBI, 18 F-GE-194 binding was significantly higher in the lesion core and significantly lower in the ipsilateral thalamus. By 40-42 d after TBI, the reduction in 18 F-GE-194 binding extended to the cortical lesion, including the perilesional cortex around the lesion core. The reduction in thalamic binding was more extensive at 40-42 d than at 5-6 d after TBI, suggesting a progressive decrease in thalamic GABA-A receptor density. Immunohistochemistry against GABA-A α1 subunit revealed a similar decrease to 18 F-GE-194 binding, particularly during the chronic phase. Conclusion: Our data support the validity of novel 18 F-GE-179 and 18 F-GE-194 radioligands for the detection of changes in active NMDA receptor and GABA-A receptor in the injured brain. These tools are useful for follow-up evaluation of secondary postinjury pathologies.

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“…Currently there is no cure nor prophylaxis available and all therapeutic choices are only symptomatic, with the goal to eliminate seizures without interfering with normal function (Glauser et al, 2013;Jacobs et al, 2009). This sparked a renewed focus on the understanding of the pathophysiology of epileptogenesis in order to reverse the epileptogenic process or cure the disorder (Pitkanen and Immonen, 2014).…”

Section: Introductionmentioning

confidence: 99%