Amyloid β-protein precursor deposition in rat hippocampus lesioned by ibotenic acid injection

Nakamura, Yu; Takeda, Masatoshi; Niigawa, Hisayoshi; Hariguchi, Shiro; Nishimura, Tsuyoshi

doi:10.1016/0304-3940(92)90656-r

Cited by 72 publications

(17 citation statements)

References 7 publications

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“…␤-APP is a protein found in the neuronal cell and is associated with the cytoskeleton's being transported by fast anterograde axonal transport (12). ␤-APP accumulation is a sensitive marker of axonal injury and dysfunction in traumatic (13), ischemic (14), or chemical (15) injury. In this study, the accumulation of ␤-APP immunostaining in cell bodies and axons with retracted processes was considered as positive for axonal disruption.…”

Section: Methodsmentioning

confidence: 99%

Distinctive Neuropathologic Alterations in the Deep Layers of the Parietal Cortex after Moderate Ischemic-Hypoxic Injury in the P3 Immature Rat Brain

et al. 2005

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Moderate focal brain hypoxic-ischemic (HI) injury in the immature P3 rat leads to loss of cortical volume and disruptions of cortical myelination. In this study, we characterized the time course and pattern of cellular degeneration, axonal disruption, astrogliosis, and microglia activation. After moderate transient unilateral hypoxia-ischemia, brains were collected at set time points and positive staining was assessed. Cellular degeneration stained with Fluoro-Jade B (FJ-B) was distributed in a columnar pattern, primarily within the deep cortical layers V-VII extending up to layer IV of the parietal cortex (pCx). FJ-B staining increased in the ipsilateral pCx 12 and 24 h (p Ͻ 0.05) after the injury. ␤-Amyloid precursor protein immunoreactivity indicating axonal disruption increased at 24 h (p Ͻ 0.05) and showed the same distribution as FJ-B. Glial fibrillary acidic protein-positive astrocytes increased dramatically within the ipsilateral pCx from 24 h (p Ͻ 0.05) to 18 d (p Ͻ 0.001) after HI injury and displayed a columnar pattern extending from the deep cortical layers to layers IV. Isolectin-B4 and ED1-labeled microglia were also increased within the ipsilateral deep pCx and underlying white matter between 12 and 24 h (p Ͻ 0.01), and increased Isolectin-B4 lasted up to 7 d after injury. These observations are consistent with the hypothesis that neuronal loss, astrogliosis, and microglia activation precede the subsequent disruption of cortical growth and myelination. This model offers new possibilities for investigating the cellular and molecular mechanisms of damage and repair after neonatal HI injury. Approximately 5-10% of infants who are born at Ͻ1500 g show severe spastic motor deficit, and an additional 25-50% exhibit less severe neurodevelopmental disabilities involving motor, cognition, and behavioral deficits (1). Neuropathologic features in the premature infant include the distinct cystic white matter lesions termed periventricular leukomalacia (PVL) and, commonly, a more subtle and diffuse lesion with loss of white matter volume and ventriculomegaly (1,2). Magnetic resonance imaging in preterm infants has revealed abnormal diffusion signal within the white matter of preterm infants with subsequent PVL (3) and also alterations in cerebral grey and white matter development (4,5). Most animal models of hypoxia-ischemia in the immature brain are pathologically relevant to the mildly preterm infant (30 -34 wk) and term infants with neuronal loss in the cortex and deeper nuclear regions, including striatum, thalamus, and hippocampus (6,7). Models that closely resemble the alterations of brain development with loss of grey matter and diffuse white matter injury with ventriculomegaly seen more frequently in the more preterm infant are less available. The P3 rat shares some similarities in terms of cortical neuronal, glial, and oligodendroglial development to Received October 3, 2003; accepted September 29, 2004

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Section: Methodsmentioning

confidence: 99%

Distinctive Neuropathologic Alterations in the Deep Layers of the Parietal Cortex after Moderate Ischemic-Hypoxic Injury in the P3 Immature Rat Brain

et al. 2005

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“…In addition to A␤, changes in the expression of APPs have been reported following various forms of brain injury, such as intraparenchymal injections of excitotoxins (Siman et al, 1989;Kawarabayashi et al, 1991;Wallace et al, 1991;Nakamura et al, 1992;Topper et al, 1995) and cerebral ischemia (Stephenson et al, 1992;Kalaria et al, 1993). Increases in immunoreactivity (IR) for APPs have also been observed in the perikarya of neurons and in damaged axons following brain trauma in both humans (Sherriff et al, 1994) and rats (Lewen et al, 1995;.…”

mentioning

confidence: 96%

Twofold overexpression of human ?-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury

et al. 1998

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By using transgenic mice that overexpress human beta-amyloid precursor proteins (APPs) at levels twofold higher than endogenous APPs, following introduction of the human APP gene in a yeast artificial chromosome (YAC), we examined the effects of controlled cortical impact (CCI) brain injury on neuromotor/cognitive dysfunction and the development of Alzheimer's disease (AD)-like neuropathology. Neuropathological analyses included Nissl-staining and immunohistochemistry to detect APPs, beta-amyloid (Abeta), neurofilament proteins, and glial fibrillary acidic protein, whereas Abeta levels were measured in brain homogenates from mice subjected to CCI and control mice by using a sensitive sandwich enzyme-linked immunosorbent assay. Twenty APP-YAC transgenic mice and 17 wild type (WT) littermate controls were anesthetized and subjected to CCI (velocity, 5 m/second; deformation depth, 1 mm). Sham (anesthetized but uninjured) controls (n = 10 APP-YAC; n = 8 WT) also were studied. Motor function was evaluated by using rotarod, inclined-plane, and forelimb/hindlimb flexion tests. The Morris water maze was used to assess memory. Although CCI induced significant motor dysfunction and cognitive deficits, no differences were observed between brain-injured APP-YAC mice and WT mice at 24 hours and 1 week postinjury. By 1 week postinjury, both cortical and hippocampal CA3 neuron loss as well as extensive astrogliosis were observed in all injured animals, suggesting that overexpression of human APPs exhibited no neuroprotective effects. Although AD-like pathology (including amyloid plaques) was not observed in either sham or brain-inj ured animals, a significant decrease in brain concentrations of only Abeta terminating at amino acid 40 (Abeta x-40) was observed following brain injury in APP-YAC mice (P < 0.05 compared with sham control levels). Our data show that the APP-YAC mice do not develop AD-like neuropathology following traumatic brain injury. This may be because this injury does not induce elevated levels of the more amyloidogenic forms of human Abeta (i.e., Abeta x-42/43) in these mice.

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“…Some reports have shown that the expression of APP is enhanced by various forms of brain injury, including traumatic (Otsuka et al, 1991), chemical (Nakamura et al, 1992) , and ischemic injury (Stephenson et al, 1992). Further, the overexpression of APP suggests the possibility of an Alzheimer disease-like pathology after traumatic brain injury (Rumble et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Expression and Cerebral Function of Amyloid Precursor Protein After Rat Traumatic Brain Injury

Itoh¹,

Imano²,

Nishida³

et al. 2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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Amyloid β-protein precursor deposition in rat hippocampus lesioned by ibotenic acid injection

Cited by 72 publications

References 7 publications

Distinctive Neuropathologic Alterations in the Deep Layers of the Parietal Cortex after Moderate Ischemic-Hypoxic Injury in the P3 Immature Rat Brain

Distinctive Neuropathologic Alterations in the Deep Layers of the Parietal Cortex after Moderate Ischemic-Hypoxic Injury in the P3 Immature Rat Brain

Twofold overexpression of human ?-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury

Expression and Cerebral Function of Amyloid Precursor Protein After Rat Traumatic Brain Injury

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