Cytoskeletal protein degradation and neurodegeneration evolves differently in males and females following experimental head injury

Kupina, Nancy C.; Detloff, Megan Ryan; Bobrowski, Walter F.; Snyder, Bradley J.; Hall, Edward D.

doi:10.1016/s0014-4886(02)00048-1

Cited by 102 publications

(86 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is an important issue, as interaction between gender and genotype may contribute to susceptibility to seizures after TBI (Kochanek et al, 2006) and gender may influence cell death after experimental TBI depending on the model used. Gender differences in CA3 cell death and hippocampal or cortical tissue damage were not observed in WT mice subjected to CCI (Bruce-Keller et al, 2007;Hall et al, 2005), but were reported in mice subjected to closed head diffuse TBI (Kupina et al, 2003). Further studies are needed to examine a potential interaction between MBL deficiency and gender in the CCI model as well as in TBI patients.…”

Section: Discussionmentioning

confidence: 89%

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Yager

You

Qin

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Mannose binding lectin (MBL) initiates complement activation and exacerbates tissue damage after systemic ischemia/reperfusion. We tested the hypothesis that MBL activates complement and worsens outcome using two levels of controlled cortical impact (CCI) in mice. After moderate CCI (0.6 mm depth), MBL immunostaining was detected on injured endothelial cells of wild-type (WT) mice and C3d was detected in MBL KO (deficient in MBL A/C) and WT mice, suggesting that MBL is dispensable for terminal complement activation after CCI. Brain neutrophils, edema, blood-brain barrier permeability, gross histopathology, and motor dysfunction were similar in injured MBL KO and WT mice. In mice subjected to mild CCI (0.2 mm), MBL KO mice had almost two-fold increased acute CA3 cell degeneration at 6 h (P < 0.01 versus WT). Naive MBL KO mice had decreased brain volume but performed similar to WT mice in two distinct Morris water maze (MWM) paradigms. However, injured MBL KO mice had impaired performance in cued platform trials (P < 0.05 versus WT), suggesting a transient nonspatial learning deficit in injured MBL KO mice. The data suggest that MBL deficiency increases susceptibility to CCI through C3-independent mechanisms and that MBL-deficient patients may be at increased risk of poor outcome after traumatic brain injury.

show abstract

Section: Discussionmentioning

confidence: 89%

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Yager

You

Qin

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…However, TBI is a complex disorder that is impossible to fully reproduce in a single model. For example, we have found significant differences between the time courses of neurodegeneration in mouse models of diffuse (Kupina et al, 2003) and focal (Hall et al, 2005a;Hall et al, 2005b) TBI. Hence, the magnitude and timing of post-traumatic secondary injury mechanisms probably varies across head injury models.…”

Section: Introductionmentioning

confidence: 92%

“…The injured mice were allowed to survive from 30 min to 7 days depending on their experimental group. For the neurochemical studies (measurement of oxidative damage markers and cytoskeletal degradation, see below), the N for each timepoint group was 8 animals based upon our experience with the variability seen with these measurements in previous studies (Hall et al, 2004;Hall et al, 2005b;Kupina et al, 2003). For each timepoint, two sham animals were included which were mice that received craniotomy but not cortical contusion.…”

Section: Mouse Model Of Controlled Cortical Impact (Focal) Traumatic mentioning

confidence: 99%

“…The different time courses of PN-mediated oxidative damage and calpain-mediated cytoskeletal degradation seen in focal and diffuse (Kupina et al, 2003) TBI models suggests that the therapeutic window and optimum treatment durations for either PN-directed antioxidant agents or calpain inhibitor treatment may differ between the two types of TBI. Summary-Our working hypothesis, based upon the findings in this study, is illustrated in Figure 6.…”

Section: Interaction Of Peroxynitrite-induced Oxidative and Calpain-mmentioning

confidence: 99%

See 1 more Smart Citation

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

133

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

“…One potential clinical application of calpain inhibitors is in the treatment of cataract. In fact, calpain inhibitors such as SJA6017 (a reversible and cell-permeable calpain inhibitor) and E-64-d, an epoxysuccinyl derivative and irreversible, general inhibitor of cysteine proteases [(L-3-trans-ethoxycarbonyloxirane-2-carbonyl)-L-leucine-(3-methylbutyl) amide] have shown anti-cataract efficacy in lens culture models (22,31,44). Transcorneal permeability of SJA6017 has been improved by introduction of cyclic hemiacetal into the chemical structure of SJA6017.…”

Section: Potential Use Of Calpain Inhibitors In Neurodegenerative Dismentioning

confidence: 99%

Involvement of Calpain Activation in Neurodegenerative Processes

et al. 2006

View full text Add to dashboard Cite

One of the challenges in the coming years will be to better understand the mechanisms of neuronal cell death with the objective of developing adequate drugs for the treatment of neurodegenerative disorders. Caspases and calpains are among the best-characterized cysteine proteases activated in brain disorders. Likewise, during the last decade, extensive research revealed that the deregulation of calpains activity is a key cytotoxic event in a variety of neurodegenerative disorders. Moreover, interest in the role of calpain in neurodegenerative processes is growing due to implication of the involvement of cdk5 in neurodegenerative diseases. Since calpain inhibitors appear to not only protect brain tissue from ischemia, but also to prevent neurotoxicity caused by such neurotoxins as â-amyloid or 3-nitropropionic acid, the currently available data suggest that calpain and cdk5 play a key role in neuronal cell death. It seems clear that the inappropriate activation of cysteine proteases occurs not only during neuronal cell death, but may also contribute to brain pathology in ischemia and traumatic brain disorders. Pharmacological modulation of calpain activation may, therefore, be useful in the treatment of neurodegenerative disorders. It is possible, although difficult, to develop synthetic inhibitors of cysteine proteases, specifically calpains. The inhibition of calpain activation has recently emerged as a potential therapeutic target for the treatment of neurodegenerative diseases. 135

show abstract

Cytoskeletal protein degradation and neurodegeneration evolves differently in males and females following experimental head injury

Cited by 102 publications

References 71 publications

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

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

Involvement of Calpain Activation in Neurodegenerative Processes

Contact Info

Product

Resources

About