Fluid percussion brain injury in the developing and adult rat: a comparative study of mortality, morphology, intracranial pressure and mean arterial blood pressure

Prins, Mayumi L.; Lee, Stefan M.; Cheng, Charles L.Y.; Becker, Donald P.; Hovda, David A.

doi:10.1016/0165-3806(96)00098-3

Cited by 161 publications

(104 citation statements)

References 52 publications

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“…Seizures were defined as abnormal posturing or spontaneous movement during the period of righting reflex suppression. Apnea was recorded when breathing ceased for greater than 5 s immediately following injury, as previous published [22]. The righting reflex time is the total time from the initial impact until the rat spontaneously rights itself from a supine position.…”

Section: Methodsmentioning

confidence: 99%

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats

Rowe¹,

Ziebell

Harrison

et al. 2016

Dev Neurosci

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Development and aging are influenced by external factors with the potential to impact health throughout the life span. Traumatic brain injury (TBI) can initiate and sustain a lifetime of physical and mental health symptoms. Over 1.7 million TBIs occur annually in the USA alone, with epidemiology suggesting a higher incidence for young age groups. Additionally, increasing life spans mean more years to age with TBI. While there is ongoing research of experimental pediatric and adult TBI, few studies to date have incorporated animal models of pediatric, adolescent, and adult TBI to understand the role of age at injury across the life span. Here, we explore repeated behavioral performance between rats exposed to diffuse TBI at five different ages. Our aim was to follow neurological morbidities across the rodent life span with respect to age at injury. A single cohort of male Sprague-Dawley rats (n = 69) was received at postnatal day (PND) 10. Subgroups of this cohort (n = 11-12/group) were subjected to a single moderate midline fluid percussion injury at age PND 17, PND 35, 2 months, 4 months, or 6 months. A control group of naïve rats (n = 12) was assembled from this cohort. The entire cohort was assessed for motor function by beam walk at 1.5, 3, 5, and 7 months of age. Anxiety-like behavior was assessed with the open field test at 8 months of age. Cognitive performance was assessed using the novel object location task at 8, 9, and 10 months of age. Depression-like behavior was assessed using the forced swim test at 10 months of age. Age at injury and time since injury differentially influenced motor, cognitive, and affective behavioral outcomes. Motor and cognitive deficits occurred in rats injured at earlier developmental time points, but not in rats injured in adulthood. In contrast, rats injured during adulthood showed increased anxiety-like behavior compared to uninjured control rats. A single diffuse TBI did not result in chronic depression-like behaviors or changes in body weight among any groups. The interplay of age at injury and aging with an injury are translationally important factors that influence behavioral performance as a quality of life metric. More complete understanding of these factors can direct rehabilitative efforts and personalized medicine for TBI survivors.

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Section: Methodsmentioning

confidence: 99%

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats

Rowe¹,

Ziebell

Harrison

et al. 2016

Dev Neurosci

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“…Caspases contribute to cell cleavage via inactivation of nuclease inhibitors and survival proteins, direct disassembly of cell structures, destruction of proteins involved in cytoskeleton regulation, and inactivation of proteins involved in DNA repair and replication. 54 Pioneering attempts to model pediatric head trauma were made by Prins and associates, 55 Prins and Hovda, 56 and Adelson and colleagues, 57,58 who adopted the lateral fluid percussion and closed head injury model, initially described by Marmarou and collaborators, 59 to 17-day-old rats. Our goal was to study the response of the rat brain to head trauma in even earlier developmental stages, and examine mechanisms that contribute to unfavorable outcomes of very young pediatric patients to head trauma.…”

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confidence: 99%

Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain

et al. 1999

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Age dependency of apoptotic neurodegeneration was studied in the developing rat brain after percussion head trauma. In 7‐day‐old rats, mechanical trauma, applied by means of a weight drop device, was shown to trigger widespread cell death in the hemisphere ipsilateral to the trauma site, which first appeared at 6 hours, peaked at 24 hours, and subsided by 5 days after trauma. Ultrastructurally, degenerating neurons displayed features consistent with apoptosis. A decrease of bcl‐2 in conjunction with an increase of c‐jun mRNA levels, which were evident at 1 hour after trauma and were accompanied by elevation of CPP 32‐like proteolytic activity and oligonucleosomes in vulnerable brain regions, confirmed the apoptotic nature of this process. Severity of trauma‐triggered apoptosis in the brains of 3‐ to 30‐day‐old rats was age dependent, was highest in 3‐ and 7‐day‐old animals, and demonstrated a subsequent rapid decline. Adjusting the mechanical force in accordance with age‐specific brain weights revealed a similar vulnerability profile. Thus, apoptotic neurodegeneration contributes in an age‐dependent fashion to neuropathological outcome after head trauma, with the immature brain being exceedingly vulnerable. These results help explain unfavorable outcomes of very young pediatric head trauma patients and imply that, in this group, an antiapoptotic regimen may constitute a successful neuroprotective approach. Ann Neurol 1999;45:724–735

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“…Following experimental brain concussion, adult animals develop severity-dependent neurological and cognitive deficits in tasks such as beam walking and spatial learning (Dixon et al, 1987;McIntosh et al, 1989;Prins et al, 1996). Additionally, experimental concussive brain injury leads to impairment in neuroplastic mechanisms such as long-term potentiation in adult animals (D'Ambrosio et al, 1998;Reeves et al, 1995;Sanders et al, 2000;Sick et al, 1998).…”

Section: Introductionmentioning

confidence: 96%

“…Additionally, experimental concussive brain injury leads to impairment in neuroplastic mechanisms such as long-term potentiation in adult animals (D'Ambrosio et al, 1998;Reeves et al, 1995;Sanders et al, 2000;Sick et al, 1998). Immature animals show minimal cognitive deficits following mild to moderate traumatic brain injury (Adelson et al, 1997;Prins et al, 1996;Prins et al, 1998), but develop dysfunctional hippocampal ionic homeostasis (D'Ambrosio et al, 1999) and impaired neuroplasticity (Fineman et al, 2000). Given this postconcussive attenuation of plasticity in the absence of substantial morphological change, we have turned our attention to investigating potential molecular mechanisms of trauma-induced neurological and developmental deficits.…”

Section: Introductionmentioning

confidence: 97%

Genes Preferentially Induced by Depolarization after Concussive Brain Injury: Effects of Age and Injury Severity

Giza

Prins

Hovda

et al. 2002

Journal of Neurotrauma

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Fluid percussion (FP) brain injury leads to immediate indiscriminate depolarization and massive potassium efflux from neurons. Using Northern blotting, we examined the post-FP expression of primary response/immediate early genes previously described as induced by depolarization in brain. RNA from ipsilateral and contralateral hippocampus was harvested from immature and adult rats 1 h following mild, moderate, or severe lateral fluid percussion injury and compared against age-matched sham animals. C-fos gene expression was used as a positive control and showed marked induction in both pups (6-25-fold with increasing severity) and adults (9.7-17.1-fold). Kinase-induced-by-depolarization-1 (KID-1) and salt-inducible kinase (SIK) gene expression was increased in adult (KID-1 1.5-1.6-fold; SIK 1.3-3.9-fold) but not developing rats. NGFI-b RNA was elevated after injury in both ages (pups 1.8-6.1-fold; adults 3.5-5-fold), in a pattern similar to that seen for c-fos. Secretogranin I (sec I) demonstrated no significant changes. Synaptotagmin IV (syt IV) was induced only following severe injury in the immature rats (1.4-fold). Our results reveal specific severity- and age-dependent patterns of hippocampal immediate early gene expression for these depolarization-induced genes following traumatic brain injury. Differential expression of these genes may be an important determinant of the distinct molecular responses of the brain to varying severities of trauma experienced at different ages.

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Fluid percussion brain injury in the developing and adult rat: a comparative study of mortality, morphology, intracranial pressure and mean arterial blood pressure

Cited by 161 publications

References 52 publications

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats

Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain

Genes Preferentially Induced by Depolarization after Concussive Brain Injury: Effects of Age and Injury Severity

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