Pediatric Traumatic Brain Injury: Quo Vadis?

Kochanek, Patrick M.

doi:10.1159/000094151

Cited by 88 publications

(49 citation statements)

References 230 publications

(130 reference statements)

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“…To model this scenario in mice we applied a closed controlled impact in P7 mice, a postnatal age which approximately corresponds to the neonatal and infant periods of child development (Yager and Thornhill, 1997;Rice and Barone, 2000;Kochanek, 2006), and studied the neuropathological changes following TBI.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the state of white matter development and myelinization in the P7 rodent is similar to that in the human infant (Craig et al, 2003). Based on these and other comparative data, immature rodents 7-14 days of age are considered to correspond to the infant age (up to 12 months) in humans, whereas rodents 17-21 days of age are equivalent to toddlers (2-3 years of age) (Yager and Thornhill, 1997;Rice and Barone, 2000;Kochanek, 2006). Accordingly, these two age groups have been widely used to model the neurodegenerative and neurophatological consequences of TBI in infants and toddlers (Adelson et al, 1996;Prins et al, 1996;Tong et al, 2002;Bittigau et al, 2003;Pullela et al, 2006;Huh et al, 2007).…”

Section: Introductionmentioning

confidence: 98%

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Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons

Dikranian

Cohen

Donald

et al. 2008

Experimental Neurology

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The immature brain in the first several years of childhood is very vulnerable to trauma. Traumatic brain injury (TBI) during this critical period often leads to neuropathological and cognitive impairment. Previous experimental studies in rodent models of infant TBI were mostly concentrated on neuronal degeneration, while axonal injury and its relationship to cell death have attracted much less attention. To address this, we developed a closed controlled head injury model in infant (P7) mice and characterized the temporospatial pattern of axonal degeneration and neuronal cell death in the brain following mild injury. Using amyloid precursor protein (APP) as marker of axonal injury we found that mild head trauma causes robust axonal degeneration in the cingulum/external capsule as early as 30 min post-impact. These levels of axonal injury persisted throughout a 24 hr period, but significantly declined by 48 hrs. During the first 24 hrs injured axons underwent significant and rapid pathomorphological changes. Initial small axonal swellings evolved into larger spheroids and clublike swellings indicating the early disconnection of axons. Ultrastructural analysis revealed compaction of organelles, axolemmal and cytoskeletal defects. Axonal degeneration was followed by profound apoptotic cell death in the posterior cingulate and retrosplenial cortex and anterior thalamus which peaked between 16 and 24 hrs post-injury. At early stages post-injury no evidence of excitotoxic neuronal death at the impact site was found. At 48 hrs apoptotic cell death was reduced and paralleled with the reduction in the number of APP-labeled axonal profiles. Our data suggest that early degenerative response to injury in axons of the cingulum and external capsule may cause disconnection between cortical and thalamic neurons, and lead to their delayed apoptotic death.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons

Dikranian

Cohen

Donald

et al. 2008

Experimental Neurology

View full text Add to dashboard Cite

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“…Decreased CSF levels of anti-apoptotic proteins and increased CSF levels of pro-apoptotic proteins have been found in children following TBI [56]. A delayed increase in CSF levels of neuron-specific enolase, suggestive of apoptotic cell death, has also been described [41,57]. More recently, a serum biomarker "trajectory," with late or sustained increases in neuron-specific enolase and consistent with apoptotic or delayed cell death, has also been demonstrated.…”

Section: How Is Tbi Different In Children?mentioning

confidence: 98%

“…Although not unique to pediatric brain injury, diffuse brain swelling is an important feature of pediatric TBI and has been reported to be 3 times as common in pediatric TBI as compared with adult TBI [40,41]. Diffuse cerebral swelling has been associated with rapid neurological deterioration and is the most common cause of brain death following severe TBI in both children and adults [42].…”

Section: How Is Tbi Different In Children?mentioning

confidence: 99%

Pediatric Neurocritical Care

Murphy

2012

Neurotherapeutics

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Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.

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“…Anderson et al (2009c) revealed results that supported the vulnerability perspective for focal injuries as well, since injury before 2 years of age was linked to global and often significant cognitive deficits, while children injured when older performed more closely to normal expectations. Kochanek (2006) argues, without specifying the type of recovery, that the plasticity concept of Kennard might be too broad for CTBI and that an optimal age-window might exist during in which neural plasticity and the associated recovery is most pronounced.…”

Section: Vulnerability Versus Plasticitymentioning

confidence: 99%

Long-term cognitive outcome of childhood traumatic brain injury

Jonsson¹

2010

PsycEXTRA Dataset

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There is limited knowledge of cognitive outcome extending beyond 5 years after childhood traumatic brain injury, CTBI. The main objectives of this thesis were to investigate cognitive outcome at 6 14 years after CTBI, and to evaluate if advancements in the neurosurgical care, starting 1992, did influence long-term outcome and early epidemiology. An additional aim was to study the relationship between early brain injury parameters and early functional outcome. Study 1 evaluated cognitive progress during 14 years after CTBI, over three neuropsychological assessments in 8 patients with serious CTBI. Study 2 used patient records to investigate early epidemiology, received rehabilitation and medical follow up in two clinical cohorts, n=82 and n=46, treated neurosurgically for CTBI before and after 1992. An exploratory cluster analysis was applied to analyse the relation between early brain injury severity parameters and early functional outcome. In Study 3, participants in the two cohorts, n=18 and n=23, treated neurosurgically for CTBI before and after 1992, were subject to an extensive neuropsychological assessment, 13 and 6 years after injury, respectively. Assessment results of the two cohorts were compared with each other and with controls. Data were analysed with multivariate analyses of variance. Results and discussion. There were significant long-term cognitive deficits of similar magnitude and character in the two cohorts with CTBI, treated before and after the advancements in neurosurgical care. At 6 14 years after injury, long-term deficits in verbal intellectual and executive functions were found, and were discussed in terms of their late maturation and a decreased executive control over verbal memory-functions after CTBI. Visuospatial functions had a slightly better long-term recovery. The amount of rehabilitation received was equally low in both cohorts. The length of time spent in intensive care and the duration of care in the respirator may have a stronger relationship to early outcome than does a single measure of level of consciousness at admission. Main conclusions are that cognitive deficits are apparent at longterm follow up, 6 13 years after neurosurgically treated CTBI, even after advancements in the neurosurgical care in Sweden. Measures of verbal IQ, verbal memory and executive functions were especially low while visuospatial intellectual functions appear to have a better long-term recovery.

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Pediatric Traumatic Brain Injury: Quo Vadis?

Cited by 88 publications

References 230 publications

Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons

Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons

Pediatric Neurocritical Care

Long-term cognitive outcome of childhood traumatic brain injury

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