A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats

Kharatishvili, Irina; Nissinen, Jari; McIntosh, Tracy K.; Pitkänen, Asla

doi:10.1016/j.neuroscience.2006.03.012

Cited by 333 publications

(384 citation statements)

References 45 publications

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“…and all seem to relate to severity on some continuum (Anderson et al, 2003;Vorst et al, 2007). Taken together, in well controlled animal models there is a continuum associated with severity of impact injury supporting the contention that injury is on a continuum (Gurkoff et al, 2006;Igarashi et al, 2007;Kharatishvili et al, 2006;Maegele et al, 2005;Ucar et al, 2006). Understanding this continuum means that at the mildest level of brain perturbation there may, in fact, be no lasting effect.…”

Section: Is Brain Injury On a Continuum: Concussion R Severe Tbi?mentioning

confidence: 79%

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Bigler

2007

J Int Neuropsychol Soc

363

248

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On the mild end of the acquired brain injury spectrum, the terms concussion and mild traumatic brain injury (mTBI) have been used interchangeably, where persistent post-concussive syndrome (PPCS) has been a label given when symptoms persist for more than three months post-concussion. Whereas a brief history of concussion research is overviewed, the focus of this review is on the current status of PPCS as a clinical entity from the perspective of recent advances in the biomechanical modeling of concussion in human and animal studies, particularly directed at a better understanding of the neuropathology associated with concussion. These studies implicate common regions of injury, including the upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial temporal lobe, fornix, and corpus callosum. Limitations of current neuropsychological techniques for the clinical assessment of memory and executive function are explored and recommendations for improved research designs offered, that may enhance the study of long-term neuropsychological sequelae of concussion. (JINS, 2008, 14, 1-22.)

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Section: Is Brain Injury On a Continuum: Concussion R Severe Tbi?mentioning

confidence: 79%

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Bigler

2007

J Int Neuropsychol Soc

363

248

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“…Given the typical sustained SGC firing, the possibility that SGCs drive early postinjury increases in dentate excitability is compatible with the contribution of polysynaptic network activity to the increase in duration of granule cell and mossy cell firing after brain injury (Santhakumar et al, 2000). Furthermore, it remains to be seen whether SGCs undergo structural plasticity of hilar and molecular layer axon collaterals analogous to the aberrant recurrent mossy fiber sprouting after brain injury (Golarai et al, 2001;Santhakumar et al, 2001;Kharatishvili et al, 2006). While the relatively sparse distribution of SGCs pose a potential caveat to its ability to transform network activity, computational analyses predict that a few highly connected neurons could serve as "hubs" that shape network behavior in epilepsy (Morgan and Soltesz, 2008).…”

Section: Discussionmentioning

confidence: 97%

Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury

Gupta¹,

Elgammal²,

Proddutur³

et al. 2012

J. Neurosci.

106

234

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Brain injury is an etiological factor for temporal lobe epilepsy and can lead to memory and cognitive impairments. A recently characterized excitatory neuronal class in the dentate molecular layer, semilunar granule cell (SGC), has been proposed to regulate dentate network activity patterns and working memory formation. Although SGCs, like granule cells, project to CA3, their typical sustained firing and associational axon collaterals suggest that they are functionally distinct from granule cells. We find that brain injury results in an enhancement of SGC excitability associated with an increase in input resistance 1 week after trauma. In addition to prolonging miniature and spontaneous IPSC interevent intervals, brain injury significantly reduces the amplitude of tonic GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in direct contrast to the increase observed in granule cells after trauma. Although our observation that SGCs express Prox1 indicates a shared lineage with granule cells, data from control rats show that SGC tonic GABA currents are larger and sIPSC interevent intervals shorter than in granule cells, demonstrating inherent differences in inhibition between these cell types. GABA A receptor antagonists selectively augmented SGC input resistance in controls but not in head-injured rats. Moreover, post-traumatic differences in SGC firing were abolished in GABA A receptor blockers. Our data show that cell-type-specific post-traumatic decreases in tonic GABA currents boost SGC excitability after brain injury. Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute substantively to the enhanced risk for epilepsy and memory dysfunction after traumatic brain injury.

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“…Justification for the selection of the baseline and monitoring periods (time points, duration) would be important to report, particularly for chronic treatments in models that demonstrate progression, evolution, or seizure clustering with relatively long intercluster periods 27, 63, 64…”

Section: Opportunities To Narrow the Preclinical‐clinical Trial Gap Amentioning

confidence: 99%

Not all that glitters is gold: A guide to critical appraisal of animal drug trials in epilepsy

Galanopoulou

Mowrey

2016

Epilepsia Open

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SummaryPreclinical studies have produced numerous drugs with antiseizure properties that currently are the standard of care. One third of the human population with epilepsy still continues to have seizures despite the ongoing discoveries. The recognized clinical gaps of care that need to be addressed are the identification of antiepileptogenic and disease‐modifying treatments, and treatments for refractory seizures or for seizures and epilepsies with limited or unsatisfactory treatments, such as early life epileptic encephalopathies. In this invited review, we provide a historical summary of the international efforts to reevaluate the strategies adopted in preclinical epilepsy therapy discovery studies. We discuss issues that may affect the quality, interpretation, and validation of preclinical studies and their translation to successful therapies for humans affected with epilepsy. These include the selection of animal models and the study design; research practices that affect rigor (such as appropriate use of statistics and reporting of study methods and results, their validation across models, labs, and preclinical‐clinical studies); the need to harmonize research methods and outcome assessment; and the importance of improving translation to clinically appropriate situations. The epilepsy research community is incrementally adopting collaborative research, including consortia or multicenter studies to meet these needs. Improving the infrastructure that can support these efforts will be instrumental in future success.

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A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats

Cited by 333 publications

References 45 publications

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury

Not all that glitters is gold: A guide to critical appraisal of animal drug trials in epilepsy

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