Microtubular Proteolysis in Focal Cerebral Ischemia

Pettigrew, L. Creed; Holtz, Mary L.; Craddock, Susan D.; Minger, Stephen; Hall, Nathan C.; Geddes, James W.

doi:10.1097/00004647-199611000-00013

Cited by 128 publications

(83 citation statements)

References 41 publications

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“…Calpain-mediated truncation of the L-type calcium channel occurs both in vitro Pettigrew et al (1996), Buddle et al (2003), and Ziemka-Na"ecz et al (2003) Abbreviations: AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; MAP, microtubule-associated protein; NMDA, N-methyl-D-aspartic acid; PSD, postsynaptic density protein; SAP-97, synapse associated protein-97. (De Jongh et al, 1994) and in hippocampal neurons exposed to NMDA (Hell et al, 1996).…”

Section: Plasma Membrane and Synapsementioning

confidence: 99%

“…Microtubule-associated protein II is susceptible to calpain-mediated cleavage, as in vivo excitotoxicity leads to calpainmediated loss of MAP2 immunoreactivity (Siman and Noszek, 1988). Similar degradation of MAP2 occurs after oxygen-glucose deprivation in hippocampal slice culture (Buddle et al, 2003) and in in vivo focal (Pettigrew et al, 1996) and global ischemia (Ziemka-Na"ecz et al, 2003). This degradation of MAP2 is preceded by calpain activation, and is prevented by calpain inhibition (Inuzuka et al, 1990).…”

Section: Plasma Membrane and Synapsementioning

confidence: 99%

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Mechanistic Role of Calpains in Postischemic Neurodegeneration

Bevers

Neumar

2007

J Cereb Blood Flow Metab

138

132

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The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular locations are explored. Calpain substrates within synapses, plasma membrane, endoplasmic reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall effect of postischemic calpain activity on calcium regulation and cell death signaling are considered. Finally, potential pathways for calpain-mediated neurodegeneration are outlined in an effort to guide future studies aimed at understanding the downstream pathology of postischemic calpain activity and identifying optimal therapeutic strategies.

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Section: Plasma Membrane and Synapsementioning

confidence: 99%

Section: Plasma Membrane and Synapsementioning

confidence: 99%

Mechanistic Role of Calpains in Postischemic Neurodegeneration

Bevers

Neumar

2007

J Cereb Blood Flow Metab

138

132

View full text Add to dashboard Cite

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“…and adult brain. This idea is supported by dynamic regulation of MAP2 expression and its involvement in dynamic changes in neuronal morphology caused by excitotoxins (Siman and Noszek, 1988;Bigot et al, 1991;Felipo et al, 1993;Arias et al, 1997;Faddis et al, 1997;Hoskison and Shuttleworth, 2006;Hoskison et al, 2007), traumatic brain injury (Taft et al, 1992;Folkerts et al, 1998), or focal ischemia (Pettigrew et al, 1996;Schwab et al, 1998). In addition, manipulations of synaptic activity alter the immunoreactivity for MAP2 in dendrites (Hendry and Bhandari, 1992;Steward and Halpain, 1999;Vaillant et al, 2002), further suggesting that synaptic activity either directly or indirectly regulates MAP2 expression.…”

mentioning

confidence: 94%

Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

Wang

Rubel

2008

Neuroscience

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Differential innervation of segregated dendritic domains in the chick nucleus laminaris (NL), composed of third-order auditory neurons, provides a unique model to study synaptic regulation of dendritic structure. Altering the synaptic input to one dendritic domain affects the structure and length of the manipulated dendrites while leaving the other set of unmanipulated dendrites largely unchanged. Little is known about the effects of neuronal input on the cytoskeletal structure of NL dendrites and whether changes in the cytoskeleton are responsible for dendritic remodeling following manipulations of synaptic inputs. In this study, we investigate changes in the immunoreactivity of high-molecular weight microtubule associated protein 2 (MAP2) in NL dendrites following two different manipulations of their afferent input. Unilateral cochlea removal eliminates excitatory synaptic input to the ventral dendrites of the contralateral NL and the dorsal dendrites of the ipsilateral NL. This manipulation produced a dramatic decrease in MAP2 immunoreactivity in the deafferented dendrites. This decrease was detected as early as three hours following the surgery, well before any degeneration of afferent axons. A similar decrease in MAP2 immunoreactivity in deafferented NL dendrites was detected following a midline transection that silences the excitatory synaptic input to the ventral dendrites on both sides of the brain. These changes were most distinct in the caudal portion of the nucleus where individual deafferented dendritic branches contained less immunoreactivity than intact dendrites. Our results suggest that the cytoskeletal protein MAP2, which is distributed in dendrites, perikarya, and postsynaptic densities, may play a role in deafferentation-induced dendritic remodeling. Keywordsdeafferentation; dendritic plasticity; afferent regulation; cytoskeleton Microtubules are a major cytoskeletal component of neuronal dendritic structure. It is well established that microtubule associated protein 2 (MAP2) binding increases the stability of the microtubule network and dendritic structure (Serrano et al., 1984;Kowalski and Williams, 1993;Yamauchi et al., 1993;Sánchez et al., 2000;Harada et al., 2002). MAP2 has been proposed to play a fundamental role as a regulator of dendritic morphology in the developing 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 errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and adult brain. This idea is supported by dynamic regulation of MAP2 expression and its involvement in dynamic changes in neuronal morphology caused by excitotoxins (Siman and Noszek, 1988;Bigot et al., 1991;Felipo et al., 199...

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“…was blinded to the coding. A three-point score was used, were 1 ϭ optimal positive MAP2 staining (no cerebral cortical tissue damage); 2 ϭ suboptimal positive MAP2 staining (minor cerebral cortical tissue damage); 3 ϭ no/minimal positive MAP2 staining (extensive cerebral cortical tissue damage and neuronal degeneration) (11,16,17).…”

Section: Methodsmentioning

confidence: 99%

Cerebral Cortical Tissue Damage After Hemorrhagic Hypotension in Near-Term Born Lambs

Tweel

Egberts

et al. 2006

Pediatr Res

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Hypotension reduces cerebral O 2 supply, which may result in brain cell damage and loss of brain cell function in the near-term neonate. The aim is to elucidate 1) to what extent the functional disturbance of the cerebral cortex, as measured with electrocortical brain activity (ECBA), is related to cerebral cortical tissue damage, as estimated by MAP2; and 2) whether there is a relationship between the glutamate, nitric oxide (NO), cGMP pathway and the development of cerebral cortical tissue damage after hemorrhagic hypotension. Seven lambs were delivered at 131 d of gestation. Hypotension was induced by withdrawal of blood until mean arterial blood pressure was reduced to 30% of normotension. Cerebral O 2 supply, consumption, and ECBA were calculated in normotensive conditions and after 2.5 h of hypotension. Concentrations of glutamate and aspartate in cerebrospinal fluid (CSF), NO 2 and NO 3 (NOx) in plasma, and cGMP in cortical brain tissue were determined in both conditions. CSF and brain tissue from siblings were used to determine normotensive values. Cortical neuronal damage was detected after 2.5 h of hypotension. ECBA was negatively related to the severity of the cortical damage. ECBA was related to respectively glutamate, NOx, and cGMP concentrations. In conclusion, cortical neuronal damage is detected after 2.5 h of hemorrhagic hypotension in the near-term born lamb. The damage is reflected by a reduction of ECBA. The glutamate, NOx, cGMP pathway is likely to be involved in the pathogenesis of cerebral cortical damage. T he developing brain requires an adequate supply of oxygen and substrates for function and growth. In immature newborns, cerebral oxygenation and hemodynamics are easily disturbed because of the immaturity of various organ systems, e.g. pulmonary and cardiovascular systems. Sufficient cerebral O 2 supply is therefore frequently jeopardized in those infants. Hypotension may diminish or disrupt the cerebral blood flow (CBF), with a consequent reduction of the supply of oxygen and substrates to the brain, thereby hindering the brain in normal functioning and growth (1).Neurons are very sensitive to reduced supplies of oxygen and glucose (2,3). Reduced cerebral O 2 supply results in a cascade of events. The excess release of excitatory amino acids, in particular glutamate, during conditions of energy failure initiates a massive influx of Ca 2ϩ into the cell. The increased intracellular Ca 2ϩ concentration triggers Ca 2ϩ -dependent processes (4), such as the formation of NO from L-arginine by nitric oxide synthase (NOS) (5). NO increases the concentrations of cyclic GMP (cGMP) through the activation of soluble guanylate cyclase (sGC) (5). Ultimately, this cascade may lead to brain cell dysfunction and cell death (6). Whereas brain cell dysfunction can be measured in vivo noninvasively by neurophysiological methods (7,8), brain cell death can only be assessed histologically. Microtubuleassociated proteins (MAP) are a diverse family of cytoskeletal proteins apparently present in all ...

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Microtubular Proteolysis in Focal Cerebral Ischemia

Cited by 128 publications

References 41 publications

Mechanistic Role of Calpains in Postischemic Neurodegeneration

Mechanistic Role of Calpains in Postischemic Neurodegeneration

Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

Cerebral Cortical Tissue Damage After Hemorrhagic Hypotension in Near-Term Born Lambs

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