Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade

Fink, Klaus; Andrews, L. John; Butler, William E.; Ona, Victor; Li, M.; Богданов, М. Б.; Endres, Matthias; Khan, Sohail Q.; Namura, Shobu; Stieg, Philip E.; Beal, M. Flint; Moskowitz, Michael A.; Yuan, Junying; Friedlander, Robert M.

doi:10.1016/s0306-4522(99)00345-0

Cited by 101 publications

(69 citation statements)

References 49 publications

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“…Transgenic mice expressing the mutant gene of caspase-1 (ICE C285G ) when subjected to CCI brain injury showed lower levels of caspase-1, reduced motor deficits, and smaller lesion volume compared with brain-injured WT mice. This neuroprotection was associated with a decrease in oxygen free radical release and was replicated by pharmacologic inhibition of caspase-1 using the selective peptide inhibitor AcYVAD-cmk and the nonselective pan-caspase inhibitor zVAD-fmk (Fink et al, 1999).…”

Section: Interleukins and Metallothioneinsmentioning

confidence: 99%

A Review and Rationale for the Use of Genetically Engineered Animals in the Study of Traumatic Brain Injury

Longhi

Saatman

Raghupathi

et al. 2001

J Cereb Blood Flow Metab

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Summary:The mechanisms underlying secondary cell death after traumatic brain injury (TBI) are poorly understood. Animal models of TBI recapitulate many clinical and pathologic aspects of human head injury, and the development of genetically engineered animals has offered the opportunity to investigate the specific molecular and cellular mechanisms associated with cell dysfunction and death after TBI, allowing for the evaluation of specific cause-effect relations and mechanistic hypotheses. This article represents a compendium of the current literature using genetically engineered mice in studies designed to better understand the posttraumatic inflammatory response, the mechanisms underlying DNA damage, repair, and cell death, and the link between TBI and neurodegenerative diseases.

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Section: Interleukins and Metallothioneinsmentioning

confidence: 99%

A Review and Rationale for the Use of Genetically Engineered Animals in the Study of Traumatic Brain Injury

Longhi

Saatman

Raghupathi

et al. 2001

J Cereb Blood Flow Metab

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“…That a less severe inflammatory challenge is also sufficient to induce acute neuronal death may have important consequences for patients with chronic neurodegenerative disease subsequently exposed to common low-grade peripheral infections. Proinflammatory cytokines, including IL-1␤ and TNF␣, are known to exacerbate neuronal damage in acute injury models (Stroemer and Rothwell, 1998), and this may occur through IL-1␤-activated pathways such as induction of inducible COX-2 (Serou et al, 1999), tissue plasminogen activator (Eberhardt et al, 2002), iNOS (Tamatani et al, 1998), and increased synthesis of the damaging reactive oxygen species superoxide and peroxynitrite (Fink et al, 1999). There is already clinical evidence that infections are deleterious in dementia.…”

Section: Mechanisms and Implicationsmentioning

confidence: 99%

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Cunningham¹,

Wilcockson²,

Campion³

et al. 2005

J. Neurosci.

676

575

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The contribution of inflammation to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion diseases is poorly understood. Brain inflammation in animal models of these diseases is dominated by chronic microglial activation with minimal proinflammatory cytokine expression. However, these inflammatory cells are "primed" to produce exaggerated inflammatory responses to subsequent lipopolysaccharide (LPS) challenges. We show that, using the ME7 model of prion disease, intracerebral challenge with LPS results in dramatic interleukin-1␤ (IL-1␤) expression, neutrophil infiltration, and inducible nitric oxide synthase expression in the brain parenchyma of prion-diseased mice compared with the same challenge in normal mice. Systemic inflammation evoked by LPS also produced greater increases in proinflammatory cytokines, pentraxin 3, and inducible nitric oxide synthase transcription in priondiseased mice than in control mice and induced microglial expression of IL-1␤. These systemic challenges also increased neuronal apoptosis in the brains of ME7 animals. Thus, both central and peripheral inflammation can exacerbate local brain inflammation and neuronal death. The finding that a single acute systemic inflammatory event can induce neuronal death in the CNS has implications for therapy in neurodegenerative diseases.

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“…Several endogenous activators and inhibitors have been described that modulate the activity of different members of the caspase family (Goyal, 2001;Shi, 2002). Caspase-1 plays an important role in pathological cell death, particularly in neurological diseases including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and cerebral ischemia (Friedlander et al, 1997a;Schielke et al, 1998;Ona et al, 1999;Zhu et al, 1999;Chen et al, 2000;Li et al, 2000b;Rabuffetti et al, 2000;Ilzecka et al, 2001;Friedlander, 2003;W.H. Zhang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Receptor Interacting Protein-2 and Caspase Recruitment Domain Only Protein Mediates Aberrant Caspase-1 Activation in Huntington's Disease

Wang

Wang²,

Figueroa³

et al. 2005

J. Neurosci.

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Caspase-1 plays a role in the pathogenesis of a variety of neurological diseases. Caspase-1 activation is an early event in models of Huntington's disease (HD). However, mechanisms regulating the activation of this apical caspase in cell death are not known. Receptor interacting protein-2 (Rip2) and caspase recruitment domain (CARD) only protein (Cop) are two CARD proteins with significant homology to the caspase-1 CARD and modulate caspase-1 activation in inflammation. Rip2 is a caspase-1 activator, and Cop is a caspase-1 inhibitor. We demonstrate in models of HD that caspase-1 activation results from dysregulation of caspase-1 activation pathways. Associated with disease progression, we detect elevation of the caspase-1 activator Rip2 and reduction of the caspase-1 inhibitor Cop. Knocking down endogenous Rip2/Cop respectively results in reduced/increased sensitivity to neurotoxic stimuli. Our data provide evidence that caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop, and alterations of this balance may contribute to aberrant caspase-1-mediated pathogenesis in Huntington's disease.

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Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade

Cited by 101 publications

References 49 publications

A Review and Rationale for the Use of Genetically Engineered Animals in the Study of Traumatic Brain Injury

A Review and Rationale for the Use of Genetically Engineered Animals in the Study of Traumatic Brain Injury

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Dysregulation of Receptor Interacting Protein-2 and Caspase Recruitment Domain Only Protein Mediates Aberrant Caspase-1 Activation in Huntington's Disease

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