Traumatic brain injury in rat produces changes of β-amyloid precursor protein immunoreactivity

Lewén, Anders; Li, Gui Lin; Nilsson, Pelle; Olsson, Yngve; Hillered, Lars

doi:10.1097/00001756-199501000-00032

Cited by 83 publications

(49 citation statements)

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“…These structures were confirmed in all areas of positive staining with APP antibody in the damaged white matter. These findings were consistent with previous descriptions of traumatic axonal injury (Gentleman et al, 1993;Lewen et al, 1995;Sherriff et al, 1994). CCI produced a large area of necrosis and tissue loss that was readily apparent histologically in mice sacrificed 4-6 hrs and 24 hrs after injury ( Figure 1C).…”

Section: Resultssupporting

confidence: 92%

“…Previous studies have shown that the histological characterization of axonal injury by neurofilament and APP immunostaining serve as complementary markers of axonal injury (Marmarou et al, 2005;Stone et al, 2001). APP, which normally traverses the length of the axon (Koo et al, 1990), accumulates at axonal retraction bulbs and varicosities in response to injury (Gentleman et al, 1993;Lewen et al, 1995;Sherriff et al, 1994;Smith et al, 1999;Stone et al, 2000;Stone et al, 2001). In addition, it is thought that the structural integrity of the axonal cytoskeleton breaks down leading to increased neurofilament immunoreactivity following injury (Grady et al, 1993;Maxwell et al, 1997;Povlishock and Katz, 2005;Stone et al, 2001;Yaghmai and Povlishock, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Donald

Dikranian

Song

et al. 2007

Experimental Neurology

277

209

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Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 hours and 24 hours post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters -axial diffusivity and relative anisotropy -were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectible on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP tained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure.Corresponding Author: David Brody, MD PhD, Department of Neurology, Washington University, 660 S. Euclid, Campus Box 8111, St. Louis, MO 63110, Phone: 314-747-0286, Fax: 314-362-2244 Email: brodyd@neuro.wustl.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose. NIH Public Access

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Donald

Dikranian

Song

et al. 2007

Experimental Neurology

277

209

View full text Add to dashboard Cite

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“…It is not known at present whether the long-lasting changes we observed in GH, IL-1b and GFAP could be upstream precursors of other pathological lesions observed post-TBI-e.g., the deposition of beta-amyloid and=or amyloid precursor proteins in the cortical regions or the neuronal loss reported in an experimental model of TBI (Lewen et al, 1995;Pierce et al, 1996;Iwata et al, 2002). It is also possible that in pediatric TBI, symptoms and deficits are exacerbated by GH deficiency occurring weeks or months after the initial insult, as happens in aged subjects (Aimaretti et al, 2005a;McDonald et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Traumatic Brain Injury Causes Long-Term Reduction in Serum Growth Hormone and Persistent Astrocytosis in the Cortico-Hypothalamo-Pituitary Axis of Adult Male Rats

Kasturi

Stein

2009

Journal of Neurotrauma

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In humans, traumatic brain injury (TBI) causes pathological changes in the hypothalamus (HT) and the pituitary. One consequence of TBI is hypopituitarism, with deficiency of single or multiple hormones of the anterior pituitary (AP), including growth hormone (GH). At present no animal model of TBI with ensuing hypopituitarism has been demonstrated. The main objective of this study was to investigate whether cortical contusion injury (CCI) could induce long-term reduction of serum GH in rats. We also tested the hypothesis that TBI to the medial frontal cortex (MFC) would induce inflammatory changes in the HT and AP. Methods: Nine young adult male rats were given sham surgery (n ¼ 4) or controlled impact contusions (n ¼ 5) of the MFC. Two months postinjury they were killed, trunk blood collected and their brains and AP harvested. GH was measured in serum and AP using ELISA and Western blot respectively. Interleukin-1b (IL-1b) and glial fibrillary acidic protein (GFAP) were measured in the cortex (Cx), HT, and AP by Western blot. Results: Lesion rats had significantly (p < 0.05) lower levels of GH in the AP and serum, unaltered serum IGF-1, and significantly (p < 0.05) higher levels of IL-1b in the Cx and HT and GFAP in the Cx, HT, and AP compared to that of shams. Conclusion: CCI leads to a long-term depletion of serum GH in male rats. This chronic change in GH post-TBI is probably the result of systemic and persistent inflammatory changes observed at the level of HT and AP, the mechanism of which is not yet known.

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“…Others have reported impaired long-term potentiation 24 fluid percussion injury in hippocampal tissue, despite no change in cortical tissue. 25 Additionally, inflammatory processes, such as early intense increased glial fibrillary acidic protein immunoreactivity, 26 upregulation of ß-Amyloid precursor protein, 27,28 alterations in regional metabolism, 29 seizures, 30 as well as hypoxia, ischemia, and hyperemia, 31,32 may further exacerbate injury in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate‐to‐severe traumatic brain injury

Wilde

Bigler

Hunter

et al. 2007

Develop Med Child Neuro

108

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While closed head injury frequently results in damage to the frontal and temporal lobes, damage to deep cortical structures, such as the hippocampus, amygdala, and basal ganglia, has also been reported. Five deep central structures (hippocampus, amygdala, globus pallidus, putamen, and caudate) were examined in 16 children (eight males, eight females; aged 9-16y), imaged 1 to 10 years after moderate-tosevere traumatic brain injury (TBI), and in 16 individuallymatched uninjured children. Analysis revealed significant volume loss in the hippocampus, amydala, and globus pallidus of the TBI group. Investigation of relative volume loss between these structures and against five cortical areas (ventromedial frontal, superomedial frontal, lateral frontal, temporal, and parieto-occipital) revealed the hippocampus to be the most vulnerable structure following TBI (i.e. greatest relative difference between the groups). In a separate analysis excluding children with focal hippocampal abnormalities (e.g. lesions), group differences in hippocampal volume were still evident, suggesting that hippocampal damage may be diffuse rather than focal.Although frontal and temporal areas have been considered most susceptible to focal injury following traumatic brain injury (TBI), deep central brain structures, such as the hippocampal/amygdalar complex and the basal ganglia, are also vulnerable to TBI-related injury. Structural neuroimaging studies of adult patients with TBI, using T 2 -weighted fast field echo (FFE), 1 T 2 -weighted 2 and susceptibility-weighted 3 gradient echo imaging pulse sequences, have recently identified increased evidence for diffuse axonal injury and 'microbleeds' in the basal ganglia and medial temporal lobes. Similarly, functional neuroimaging has implicated deep central areas, with evidence of long-term reduction in cerebral blood flow, 4 hypoperfusion, 5 and decreased cerebral metabolic rate 6 in the basal ganglia/striatum following TBI. Medial temporal lobe vulnerability is also suggested by positron emission tomography and single-photon emission computed tomography, 7 with an association between brain injuryinduced abnormalities and neurocognitive deficits. Finally, proton magnetic resonance spectroscopy has revealed a significantly decreased N-acetylaspartate/choline ratio in the basal ganglia and hippocampus of patients with TBI. 8 Quantitative magnetic resonance imaging (MRI) studies of adult patients with TBI have found hippocampal atrophy which correlated with injury severity as measured by the Glasgow Coma Scale score. 9-12 However, only three studies have examined hippocampal volume in individuals experiencing TBI as children or adolescents, [13][14][15] and only a single study has examined caudate volume in this population. 14 Despite growing evidence of injury to the amygdala and the basal ganglia from various mechanisms, there has been no examination of the amygdala, globus pallidus, or putamen using quantitative brain imaging in pediatric patients with TBI. This absence is notable, given that thes...

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Traumatic brain injury in rat produces changes of β-amyloid precursor protein immunoreactivity

Cited by 83 publications

References 0 publications

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Traumatic Brain Injury Causes Long-Term Reduction in Serum Growth Hormone and Persistent Astrocytosis in the Cortico-Hypothalamo-Pituitary Axis of Adult Male Rats

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate‐to‐severe traumatic brain injury

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