Epileptic seizure activity in the acute phase following cortical impact trauma in rat

Nilsson, Pelle; Ronne-Engström, Elisabeth; Flink, Roland; Ungerstedt, Urban; Carlson, Hans; Hillered, Lars

doi:10.1016/0006-8993(94)91237-8

Cited by 127 publications

(72 citation statements)

References 27 publications

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“…Using TBI as an example, we showed robust tissue responses to physiologically relevant impact forces. The brain-like tissue model exhibited injury-induced Glu release and transient hyperactivity that are consistent with in vivo studies (28)(29)(30)(31)(32)(33). Whereas realtime monitoring of electrophysiological activities of the brain is prohibitive with human or animal subjects, this model provides a unique opportunity for mapping out the temporal evolution of neurophysiological events and functional studies in vitro.…”

Section: Discussionsupporting

confidence: 73%

“…The similarity of the brain-like tissue mechanical properties with those of rodent brains suggested use as a model for mechanical injuries, such as TBI. In particular, the 3D brain-like tissue could provide real-time concurrent functional assessments that cannot be readily performed on patients or animals [for example, injuryinduced surge of excitatory neurotransmitter Glu (28-31) and transient seizure activities post-TBI (32,33)]. The 3D brain-like tissue allowed us to examine multiple end points postinjury, including cellular damage, electrophysiological activity, and neurochemical changes in real time (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Bioengineered functional brain-like cortical tissue

Tang-Schomer¹,

White²,

Tien³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

261

299

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The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.electrophysiology | connectivity | silk | scaffold | traumatic brain injury

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Section: Discussionsupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Bioengineered functional brain-like cortical tissue

Tang-Schomer¹,

White²,

Tien³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

261

299

View full text Add to dashboard Cite

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“…Susceptibility for either kainic acid or pentylenetetrazole induced seizures is increased after TBI in adult rats (Golarai, et al, 2001;Zanier, et al, 2003). Spontaneous generalized tonic clonic seizures are reported immediately after TBI in adult rats and adenosine A1 A receptor knock-out mice (Kochanek, et al, 2006;Nilsson, et al, 1994). Post-traumatic epilepsy is reported after TBI induced by fluid percussion injury in both adolescent and adult rats (D'Ambrosio, et al, 2004;D'Ambrosio, et al, 2005;Kharatishvili, et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Post-traumatic epilepsy is reported after TBI induced by fluid percussion injury in both adolescent and adult rats (D'Ambrosio, et al, 2004;D'Ambrosio, et al, 2005;Kharatishvili, et al, 2006). The mechanisms underlying neuronal excitability, increased seizure susceptibility, and spontaneous seizures post-TBI have not been well defined, but may include the acute release of excitatory amino acids, altered NMDA receptor expression, inhibitory interneuron loss, mossy fiber sprouting, and/or gliosis (D 'Ambrosio, et al, 2004;Giza, et al, 2006;Nilsson, et al, 1994;Statler, 2006). In adult rats, post-traumatic dentate gyrus hyperexcitability is specifically associated with mossy fiber sprouting and inhibitory interneuron loss (Golarai, et al, 2001;Statler, 2006;Toth, et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Traumatic brain injury during development reduces minimal clonic seizure thresholds at maturity

et al. 2008

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Post-traumatic seizures affect 12 -35% of children after traumatic brain injury (TBI) and are associated with worse cognitive and functional outcome, even after adjustment for severity of injury. Unfortunately, experimental models of pediatric post-traumatic epilepsy are lacking, and pathogenesis remains poorly understood. We have applied a standard model of TBI in immature rats to determine the effect of TBI on electroconvulsive seizure thresholds later in life.Male rats underwent controlled cortical impact to left parietal cortex on post-natal day (PND) 16-18. Hindbrain, forebrain, and limbic seizure thresholds were assessed, respectively, by tonic hindlimb extension (THE), minimal clonic, and partial psychomotor seizure responses during adolescence and at maturity (PND 60 -63). Post-traumatic seizure thresholds were compared to those obtained in age-and litter-matched sham craniotomy and naïve controls.TBI during immaturity had no clear effect on THE seizure thresholds. In contrast, TBI lowered minimal clonic seizure thresholds at maturity (p < 0.05 vs. sham or naïve rats), but not during adolescence. Consequently, minimal clonic seizure thresholds increased with age for sham and naïve rats but remained similar for TBI rats during adolescence and at maturity. TBI also tended to lower partial psychomotor seizure thresholds, which were determined only during adolescence (p < 0.1 vs. naive).Controlled cortical impact causes both focal cortical injury at the site of impact and ipsilateral hippocampal neuronal death. Since minimal clonic seizures are mediated by the forebrain, partial psychomotor seizures by the limbic system, and THE seizures by the brainstem, the observed pattern of changes in post-traumatic seizure thresholds is not surprising. The apparent age-dependent effects of TBI, however, are unexpected and likely due to a combination of attenuated maturational increases

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“…Studies of energy metabolism after human and rodent TBI demonstrate large dynamic changes occurring within the first hour after TBI, such that a hypermetabolic state lasting only 30 min (in rats) to a few hours (in humans) is followed by a profound depression lasting 5 and Ն30 days in rats and humans, respectively (19)(20)(21). Epileptic activity and reductions in ATP content are also restricted to the acute phase after brain injury in rats (22,23). These combined observations led us to hypothesize that NMDAR may undergo similarly large and dynamic changes in availability and responsiveness after TBI.…”

mentioning

confidence: 99%

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Biegon

Fry

Paden

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

220

164

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Traumatic brain injury is a leading cause of mortality and morbidity among young people. For the last couple of decades, it was believed that excess stimulation of brain receptors for the excitatory neurotransmitter glutamate was a major cause of delayed neuronal death after head injury, and several major clinical trials in severely head injured patients used blockers of the glutamate N-methyl-D-aspartate (NMDA) receptor. All of these trials failed to show efficacy. Using a mouse model of traumatic brain injury and quantitative autoradiography of the activity-dependent NMDA receptor antagonist MK801, we show that hyperactivation of glutamate NMDA receptors after injury is short-lived (<1 h) and is followed by a profound and long-lasting (>7 days) loss of function. Furthermore, stimulation of NMDA receptors by NMDA 24 and 48 h postinjury produced a significant attenuation of neurological deficits (blocked by coadministration of MK801) and restored cognitive performance 14 days postinjury. These results provide the underlying mechanism for the well known but heretofore unexplained short therapeutic window of glutamate antagonists after brain injury and support a pharmacological intervention with a relatively long (>24 h) time window easily attainable for treatment of human accidental head injury.H ead trauma is a leading cause of mortality and morbidity among young people in the western world (1). Traumatic and ischemic brain injury triggers a large, transient increase in excitatory amino acid transmitter efflux in the brain of experimental animals and human subjects (2-6). Glutamate activation of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which is a ligand-gated ion (calcium and sodium) channel, results in channel opening and ion influx into the cell. It has been suggested that this process mediates delayed excitotoxic neuronal death after brain ischemia and trauma (7,8), although the concept is not universally accepted (9, 10). Support for the involvement of NMDAR activation in neuronal death after brain injury has come from numerous studies showing that NMDAR antagonists reduce cell death and improve outcome in animal models of traumatic brain injury (TBI) and stroke. NMDAR antagonists appear to be most efficacious when given before or immediately after the insult and lose efficacy if administered Ͼ30-60 min postinjury (11)(12)(13)(14)(15).Microdialysis studies of extracellular glutamate in human TBI and stroke patients suggested that the increase in glutamate in humans is more sustained [6 h to several days (7, 8)] than in rodents, where it only lasts minutes (2-6). This result may have contributed to a decision to administer NMDAR antagonists in clinical trials of head injury for several days rather than once after severe nonpenetrating injury. All clinical trials of NMDAR antagonists to date failed to show efficacy. Furthermore, some of these trials had to be stopped prematurely because of increases in mortality and morbidity in the drug arm of the stroke trials (16-18), suggesting that prolonged bloc...

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Epileptic seizure activity in the acute phase following cortical impact trauma in rat

Cited by 127 publications

References 27 publications

Bioengineered functional brain-like cortical tissue

Bioengineered functional brain-like cortical tissue

Traumatic brain injury during development reduces minimal clonic seizure thresholds at maturity

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

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