Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice

Thompson, Stephanie; Gibson, Tonya; Thompson, Brian M.; Deng, Ying; Hall, Edward D.

doi:10.1016/j.expneurol.2006.04.013

Cited by 77 publications

(83 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, for these two reasons, we have more confidence in the accuracy of the current results in regards to the time course of post-traumatic cytoskeletal degradation. Furthermore, the current time course of α-spectrin degradation in the CCI-injured cortex is similar in pattern to the time course of α-spectrin degradation we have seen in the injured hippocampus using the same injury device, injury severity and infrared imaging of the blots (Thompson et al, 2006) Quantitative Post-Traumatic Time Course of Neurodegeneration Figure 5 shows the quantitative de Olmos aminocupric silver staining analysis of neurodegeneration in the ipsilateral hemisphere of mice subjected to CCI along with histological examples of the spatial and temporal characteristics of silver staining between 6 hrs and 7 days after injury. At 6 hrs after injury, there was a significant increase of silver staining volume compared to minimal level seen in sham, non-injured mouse brains.…”

Section: Quantitative Post-traumatic Time Course Of Calpain-mediated supporting

confidence: 75%

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Deng

Thompson

Gao

et al. 2007

Experimental Neurology

135

171

View full text Add to dashboard Cite

We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time-course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 hrs, 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca ++ -activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein α-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 hrs before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. α-Spectrin breakdown products, which was used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 hrs post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 hrs post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca ++ homeostatic mechanisms which causes a massive Ca ++ overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.

show abstract

Section: Quantitative Post-traumatic Time Course Of Calpain-mediated supporting

confidence: 75%

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Deng

Thompson

Gao

et al. 2007

Experimental Neurology

135

171

View full text Add to dashboard Cite

show abstract

“…Similar results have been found in MS lesions [33] and in the brains of Alzheimer's patients [34], reflecting a loss of plasticity of functionally impaired neurones. Furthermore, severe CNS injury in mice leads to diminished GAP-43 expression, reflecting the loss of endogenous repair mechanisms [35].…”

Section: Discussionmentioning

confidence: 99%

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor‐1 knockout mice: the effect of fibrinolysis during neuroinflammation

East

Gverić

Baker

et al. 2007

Neuropathology Appl Neurobio

View full text Add to dashboard Cite

During neuroinflammation in multiple sclerosis (MS) fibrinogen, not normally present in the brain or spinal cord, enters the central nervous system through a compromised blood-brain barrier. Fibrin deposited on axons is ineffectively removed by tissue plasminogen activator (tPA), a key contributory factor being the upregulation of plasminogen activator inhibitor-1 (PAI-1). Aims: This study investigated the role of PAI-1 during experimental neuroinflammatory disease. Methods: Chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of MS, was induced with spinal cord homogenate in PAI-1 knockout (PAI-1 -/-) and wild type (WT) mice, backcrossed onto the Biozzi background. Results: Disease incidence and clinical severity were reduced in PAI-1 -/-mice, with animals developing clinical signs significantly later than WTs. Clinical relapses were absent in PAI-1 -/-mice and the subsequent reduction in neuroinflammation was coupled with a higher capacity for fibrinolysis in spinal cord samples from PAI-1 -/-mice, in association with increased tPA activity. Axonal damage was less apparent in PAI-1 -/-mice than in WTs, implicating fibrin in both inflammatory and degenerative events during CREAE. Conclusions: PAI-1 is a potential target for therapy in neuroinflammatory degenerative diseases, allowing effective fibrin removal and potentially reducing relapse rate and axonal damage.

show abstract

“…In TBI models, markers of plasticity measured early post-injury are typically increased in more mild injury models like FPI, versus more severe models such as CCI (Hall and Lifshitz, 2010;Thompson et al, 2006). For example, expression of GAP-43 in the ipsilateral cortex following severe CCI is depressed (Thompson et al, 2006), whereas mild FPI results in increased GAP-43 expression out to 28 days post-injury (Hall and Lifshitz, 2010). In the current study, the injury produced by CCI would be categorized as moderate to severe, and therefore early decreases in plasticity markers would be consistent with the literature.…”

Section: Figmentioning

confidence: 99%

“…However, as in TBI, these neuronal growth responses are very sensitive to the size and extent of damage (Hsu and Jones, 2006). In TBI models, markers of plasticity measured early post-injury are typically increased in more mild injury models like FPI, versus more severe models such as CCI (Hall and Lifshitz, 2010;Thompson et al, 2006). For example, expression of GAP-43 in the ipsilateral cortex following severe CCI is depressed (Thompson et al, 2006), whereas mild FPI results in increased GAP-43 expression out to 28 days post-injury (Hall and Lifshitz, 2010).…”

Section: Figmentioning

confidence: 99%

“…In studies of the hippocampus, measures of gene expression, dendritic structure, and long-term potentiation (LTP) indicate that reactive neural plasticity can be remarkably limited after TBI (Ansari et al, 2008a;Li et al, 2004;Phillips and Reeves, 2001;Scheff et al, 2005). In neocortex, growth-associated protein-43 (GAP-43, a marker of axonal growth) does not increase, at least within 21 days post-CCI (Thompson et al, 2006), and synaptic proteins, such as post-synaptic density protein 95 (PSD-95), synapse-associated protein-07 (SAP-07), and synapsin I, decrease in a time-dependent manner out to 96 h post-CCI (Ansari et al, 2008b). These instances of decreased plasticity following TBI may be related to the upregulation of inhibitory molecules such as Nogo-A.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

Jones

Liput

Maresh

et al. 2012

Journal of Neurotrauma

View full text Add to dashboard Cite

Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.

show abstract

Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice

Cited by 77 publications

References 86 publications

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor‐1 knockout mice: the effect of fibrinolysis during neuroinflammation

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

Contact Info

Product

Resources

About