Exciting Your Neurons to Death: Can We Prevent Cell Loss after Brain Injury?

Duhaime, Ann‐Christine

doi:10.1159/000120825

Cited by 14 publications

(4 citation statements)

References 30 publications

(35 reference statements)

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“…5,7,9 Several categories of excitatory amino acid inhibitors exist: pre- and postsynaptic blockers, which inhibit the activation of different receptors; competitive antagonists, which bind directly to the receptor site; and noncompetitive antagonists. 7,13 In 2004 a Cochrane review was conducted to assess the efficacy of excitatory amino acid inhibitors in improving outcome following TBI in humans.…”

Section: Discussionmentioning

confidence: 99%

Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury

Chamoun

Suki

Gopinath

et al. 2010

JNS

214

138

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Object Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors’ objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value. Methods A prospective study of patients with severe TBI was conducted with an inclusion criterion of a Glasgow Coma Scale score ≤ 8 within 48 hours of injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO2, jugular venous O2 saturation, and cerebral microdialysis. Patients received standard care including mass evacuation when indicated and treatment of elevated intracranial pressure values. Demographic data, CT findings, and outcome at 6 months of follow-up were recorded. Results One hundred sixty-five patients were included in the study. Initially high glutamate values were predictive of a poor outcome. The mortality rate was 30.3% among patients with glutamate levels > 20 µmol/L, compared with 18% among those with levels ≤ 20 µmol/L. Two general patterns were recognized: Pattern 1, glutamate levels tended to normalize over the monitoring period (120 hours); and Pattern 2, glutamate levels tended to increase with time or remain abnormally elevated. Patients showing Pattern 1 had a lower mortality rate (17.1 vs 39.6%) and a better 6-month functional outcome among survivors (41.2 vs 20.7%). Conclusions Glutamate levels measured by microdialysis appear to have an important role in TBI. Data in this study suggest that glutamate levels are correlated with the mortality rate and 6-month functional outcome.

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Section: Discussionmentioning

confidence: 99%

Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury

Chamoun

Suki

Gopinath

et al. 2010

JNS

214

138

View full text Add to dashboard Cite

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“…Preliminary studies of agents for combatting delayed brain injury in children are underway [65], Concern has been expressed regarding whether we can measure the outcome of therapy in these investigations [66], We would propose the incidence and severity of delayed and pro gressive lesions on serial CT scans as suitable outcome parameters.…”

Section: Discussionmentioning

confidence: 99%

Delayed and Progressive Brain Injury in Children and Adolescents with Head Trauma

Stein

Spettell

1995

Pediatr Neurosurg

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We performed serial CT scans on 351 children and adolescents with serious closed-head injury. Delayed or progressive lesions were encountered in 145 (41%). The occurrence of such delayed cerebral injuries correlated with the severity of the initial head trauma, with the presence of major extracranial injury and with studies of coagulopathy on admission. The presence of delayed cerebral injury had a profound influence on survival and recovery from head trauma, especially when the initial severity of the head injury was taken into account. We conclude that serial CT scans provide a reliable means of diagnosing and following the progress of delayed cerebral injury in the pediatric population.

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“…Glutamate reuptake is diminished due to the ionic imbalance, and the concentration is further elevated. The increase in calcium ion leads to neuronal death, while the efflux of potassium ion leads to swelling in the brain [72]. Neuroprotective therapy is aimed at interrupting the excitotoxic cascade in brain tissues before neuronal toxicity is irreversible [70], leading to a reduction in severity of damage.…”

Section: Neuroprotective Approachesmentioning

confidence: 99%

Emerging treatments for traumatic brain injury

Xiong

Mahmood

Chopp

2009

Expert Opinion on Emerging Drugs

242

190

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Background This review summarizes promising approaches for the treatment of traumatic brain injury (TBI), which are either in preclinical or clinical trials. Objective The pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented. Methods A literature review of pre-clinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided. Results/conclusion Nearly all phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials which seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.

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Exciting Your Neurons to Death: Can We Prevent Cell Loss after Brain Injury?

Cited by 14 publications

References 30 publications

Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury

Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury

Delayed and Progressive Brain Injury in Children and Adolescents with Head Trauma

Emerging treatments for traumatic brain injury

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