scholarly journals Novel Strategy for Treatment of Viral Central Nervous System Infection by Using a Cell-Permeating Inhibitor of c-Jun N-Terminal Kinase

2007 ◽  
Vol 81 (13) ◽  
pp. 6984-6992 ◽  
Author(s):  
J. David Beckham ◽  
Robin J. Goody ◽  
Penny Clarke ◽  
Christophe Bonny ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Encephalitis ◽  
Viral Infections ◽  
Lethal Dose ◽  
Central Nervous System Infection ◽  
Cns Injury ◽  
Lethal Challenge ◽  
Reovirus Infection ◽  
A Cell

ABSTRACT Viral encephalitis is a major cause of morbidity and mortality worldwide, yet there is no proven efficacious therapy for most viral infections of the central nervous system (CNS). Many of the viruses that cause encephalitis induce apoptosis and activate c-Jun N-terminal kinase (JNK) following infection. We have previously shown that reovirus infection of epithelial cell lines activates JNK-dependent apoptosis. We now show that reovirus infection resulted in activation of JNK and caspase-3 in the CNS. Treatment of reovirus-infected mice with a cell-permeating peptide that competitively inhibits JNK activity resulted in significantly prolonged survival of intracerebrally infected mice following an otherwise lethal challenge with T3D (100× 50% lethal dose). Protection correlated with reduced CNS injury, reduced neuronal apoptosis, and reduced c-Jun activation without altering the viral titer or viral antigen distribution. Given the efficacy of the inhibitor in protecting mice from viral encephalitis, JNK inhibition represents a promising and novel treatment strategy for viral encephalitis.

scholarly journals Mitochondrial p53 Contributes to Reovirus-Induced Neuronal Apoptosis and Central Nervous System Injury in a Mouse Model of Viral Encephalitis

2016 ◽  
Vol 90 (17) ◽  
pp. 7684-7691 ◽  
Author(s):  
Yonghua Zhuang ◽  
Heather M. Berens-Norman ◽  
J. Smith Leser ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Fate ◽  
Tissue Injury ◽  
Ex Vivo ◽  
P53 Protein ◽  
Cns Injury ◽  
Expression Levels ◽  
Reovirus Infection ◽  
Protein Levels

ABSTRACTThe tumor suppressor p53 plays a critical part in determining cell fate both as a regulator of the transcription of several proapoptotic genes and through its binding interactions with Bcl-2 family proteins at mitochondria. We now demonstrate that p53 protein levels are increased in infected brains during reovirus encephalitis. This increase occurs in the cytoplasm of reovirus-infected neurons and is associated with the activation of caspase 3. Increased levels of p53 in reovirus-infected brains are not associated with increased expression levels of p53 mRNA, suggesting that p53 regulation occurs at the protein level. Increased levels of p53 are also not associated with the increased expression levels of p53-regulated, proapoptotic genes. In contrast, upregulated p53 accumulates in mitochondria. Previous reports demonstrated that the binding of p53 to Bak at mitochondria causes Bak activation and results in apoptosis. We now show that Bak is activated and that activated Bak is bound to p53 during reovirus encephalitis. In addition, survival is enhanced in reovirus-infected Bak−/−mice compared to controls, demonstrating a role for Bak in reovirus pathogenesis. Inhibition of the mitochondrial translocation of p53 with pifithrin μ prevents the formation of p53/Bak complexes following reovirus infection ofex vivobrain slice cultures and results in decreased apoptosis and tissue injury. These results suggest that the mitochondrial localization of p53 regulates reovirus-induced pathogenesis in the central nervous system (CNS) through its interactions with Bak.IMPORTANCEThere are virtually no specific treatments of proven efficacy for virus-induced neuroinvasive diseases. A better understanding of the pathogenesis of virus-induced CNS injury is crucial for the rational development of novel therapies. Our studies demonstrate that p53 is activated in the brain following reovirus infection and may provide a therapeutic target for virus-induced CNS disease.

scholarly journals An unusual presentation of encephalitis which mimicked generalised tetanus

2021 ◽  
Vol 8 (7) ◽  
pp. 1319
Author(s):  
Anushree M. Benny ◽  
Rajendra Prasad Nagar ◽  
Gautam Lal Nagori
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Movement Disorders ◽  
Viral Encephalitis ◽  
Central Nervous System Infection ◽  
Muscle Spasm ◽  
Temporal Lobes ◽  
Csf Analysis ◽  
Intravenous Acyclovir ◽  
New Onset

Movement disorders are frequent mimickers of more severe neurological presentations, whenever it is diagnosed one should suspect a central nervous system infection as an underlying cause. A 11 year old girl presented in casuality with intermittent generalised muscle spasm, clear sensorium, trismus and risus sardonicus. Initially managed as a case of tetanus, rapid resolution of spasms made suspicion of encephalitis as underlying cause of dystonia which mimicked tetanus. Blood investigation and CSF analysis were normal. CECT brain showed hyper dense lesions bilateral temporal lobes suggestive of viral encephalitis. Child was managed with intravenous acyclovir and dexamethasone after which child improved considerably. Acute dystonia is a close mimicker of tetanus. Any patient presenting with new onset movement disorder should be investigated for central nervous system infection even though it has been reported as a rare cause for the same.

scholarly journals Community-acquired Klebsiella pneumoniae central nervous system infection after acute suppurative otitis

IDCases ◽  
2021 ◽  
Vol 23 ◽  
pp. e01016
Author(s):  
Ruixue Sun ◽  
Hui Zhang ◽  
Yingchun Xu ◽  
Huadong Zhu ◽  
Xuezhong Yu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Klebsiella Pneumoniae ◽  
Central Nervous System Infection

scholarly journals Neonatal Ureaplasma parvum meningitis complicated with subdural hematoma: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Canyang Zhan ◽  
Lihua Chen ◽  
Lingling Hu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Subdural Hematoma ◽  
Central Nervous System Infection ◽  
Neonatal Meningitis ◽  
High Morbidity ◽  
Ureaplasma Parvum ◽  
Protein Levels ◽  
Csf Analysis ◽  
Empirical Antibiotics

Abstract Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

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