scholarly journals 867. Upregulated Matrix Metalloproteinase-2 Relates to Milder Hearing Impairment in Bacterial Meningitis

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S23-S23
Author(s):  
Okko Savonius ◽  
Irmeli Roine ◽  
Saeed Alassiri ◽  
Taina Tervahartiala ◽  
Otto Helve ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Matrix Metalloproteinase ◽  
Hearing Impairment ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Pure Tone Audiometry ◽  
Protective Role ◽  
Matrix Metalloproteinase 2 ◽  
Previous Clinical Trial ◽  
Brain Stem Evoked Response

Abstract Background Hearing impairment is a well-recognized sequela caused by bacterial meningitis, but the underlying pathophysiology remains largely unknown. Matrix metalloproteinase-2 (MMP-2) is known to affect neuronal cell damage and survival in different diseases of the brain. We investigated whether levels of MMP-2 in the cerebrospinal fluid (CSF) relate to the extent of hearing impairment in children with bacterial meningitis. Methods Clinical data of 179 children were obtained from a previous clinical trial examining the adjuvant treatment of bacterial meningitis in Latin America in 1996–2003. At discharge or shortly thereafter, the ability to hear was measured with brain stem evoked response audiometry or traditional pure tone audiometry. Levels of CSF MMP-2 on admission (CSF1, n = 161) and 12–24 hours later (CSF2, n = 133) were assessed by zymography. The combined results for the detected pro-form and active MMP-2 were compared with the audiological outcome of the patients. Results MMP-2 was detected in half of both the CSF1 and CSF2 samples. The median densitometric values with interquartile ranges (IQRs) were 0.04 (IQR 0.00–0.29) for CSF1 and 0.00 (IQR 0.00–0.33) for CSF2. Detectable MMP-2 associated with milder hearing impairment in CSF1 (P = 0.05), but not in CSF2 (P = 0.1). Patients who were deaf at discharge had lower levels of MMP-2 in both samples (CSF1, P = 0.05; CSF2, P = 0.04), compared with patients who were not deaf. A MMP-2 level over the 75th percentile in CSF1 predicted lower odds of any audiological sequelae (odds ratio 0.30, 95% confidence interval 0.14–0.68, P = 0.004). Conclusion The upregulation of MMP-2 in the CSF associated with a better audiological outcome in children with bacterial meningitis. The results suggest that MMP-2 might play a protective role in the development of hearing sequelae due to bacterial meningitis. Disclosures All authors: No reported disclosures.

scholarly journals Matrix metalloproteinase-9-mediated tissue injury overrides the protective effect of matrix metalloproteinase-2 during colitis

2009 ◽  
Vol 296 (2) ◽  
pp. G175-G184 ◽  
Author(s):  
Pallavi Garg ◽  
Matam Vijay-Kumar ◽  
Lixin Wang ◽  
Andrew T. Gewirtz ◽  
Didier Merlin ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Protective Role ◽  
Matrix Metalloproteinase 2 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Myeloperoxidase Activity ◽  
Double Knockout ◽  
Gut Barrier Function

Matrix metalloproteinases (MMP) play an important role in pathogenesis of inflammatory bowel disease (IBD). Two known gelatinases, MMP-2 and MMP-9, are upregulated during IBD. Epithelial-derived MMP-9 is an important mediator of tissue injury in colitis, whereas MMP-2 protects against tissue damage and maintains gut barrier function. It has been suggested that developing strategies to block MMP-9 activity in the gut might be of benefit to IBD. However, given that MMP-2 and MMP-9 are structurally similar, such approaches would also likely inhibit MMP-2. Thus, to gain insight into outcome of inhibiting both MMP-2 and MMP-9, MMP-2−/−/MMP-9−/− double knockout mice (dKO) lacking both MMP-2 and MMP-9 were used in this study. Three models of murine colitis were used: dextran sodium sulfate (DSS), Salmonella typhimurium (S.T.), and trinitrobenzene sulfonic acid (TNBS). Our data demonstrate that MMP-2 and MMP-9 activities were highly upregulated in wild-type (WT) mice treated with DSS, S.T., or TNBS whereas dKO mice were resistant to the development of colitis. WT mice had extensive inflammation and tissue damage compared with dKO mice as suggested by histological assessment and myeloperoxidase activity. In conclusion, these results suggest an overriding role of MMP-9 in mediating tissue injury compared with the protective role of MMP-2 in development of colitis. Thus inhibition of MMP-9 may be beneficial in treatment of colitis even if resulting in inhibition of MMP-2.

scholarly journals Protective Role of Matrix Metalloproteinase-2 in Allergic Bronchial Asthma

2019 ◽  
Vol 10 ◽  
Author(s):  
Yoshinori Takahashi ◽  
Tetsu Kobayashi ◽  
Corina N. D'Alessandro-Gabazza ◽  
Masaaki Toda ◽  
Kentaro Fujiwara ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Bronchial Asthma ◽  
Protective Role ◽  
Matrix Metalloproteinase 2 ◽  
Allergic Bronchial Asthma

scholarly journals Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling

2020 ◽  
Vol 21 (8) ◽  
pp. 2672 ◽  
Author(s):  
Sang Jin Kim ◽  
Min Jea Shin ◽  
Dae Won Kim ◽  
Hyeon Ji Yeo ◽  
Eun Ji Yeo ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Mapk Signaling ◽  
Protective Role ◽  
Mitogen Activated Protein Kinase ◽  
Biliverdin Reductase ◽  
Hippocampal Cell ◽  
Antioxidant Function ◽  
Mitogen Activated Protein

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H2O2-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.

scholarly journals Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Shyama Nandakumar ◽  
Emily Rozich ◽  
Laura Buttitta
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Protective Role ◽  
Cellular Growth ◽  
Model Organisms ◽  
Differentiated Cells ◽  
Cell Cycle Reentry

Terminally differentiated cells of the nervous system have long been considered to be in a stable non-cycling state and are often considered to be permanently in G0. Exit from the cell cycle during development is often coincident with the differentiation of neurons, and is critical for neuronal function. But what happens in long lived postmitotic tissues that accumulate cell damage or suffer cell loss during aging? In other contexts, cells that are normally non-dividing or postmitotic can or re-enter the cell cycle and begin replicating their DNA to facilitate cellular growth in response to cell loss. This leads to a state called polyploidy, where cells contain multiple copies of the genome. A growing body of literature from several vertebrate and invertebrate model organisms has shown that polyploidy in the nervous system may be more common than previously appreciated and occurs under normal physiological conditions. Moreover, it has been found that neuronal polyploidization can play a protective role when cells are challenged with DNA damage or oxidative stress. By contrast, work over the last two and a half decades has discovered a link between cell-cycle reentry in neurons and several neurodegenerative conditions. In this context, neuronal cell cycle re-entry is widely considered to be aberrant and deleterious to neuronal health. In this review, we highlight historical and emerging reports of polyploidy in the nervous systems of various vertebrate and invertebrate organisms. We discuss the potential functions of polyploidization in the nervous system, particularly in the context of long-lived cells and age-associated polyploidization. Finally, we attempt to reconcile the seemingly disparate associations of neuronal polyploidy with both neurodegeneration and neuroprotection.

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