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Neuroprotection mediated by inhibition of calpain during acute viral encephalitis.
Howe, Charles L; LaFrance-Corey, Reghann G; Mirchia, Kanish; Sauer, Brian M; McGovern, Renee M; Reid, Joel M; Buenz, Eric J.
Afiliação
  • Howe CL; Departments of Neurology, Mayo Clinic, Rochester, Minnesota, 55905 USA.
  • LaFrance-Corey RG; Departments of Neuroscience, Mayo Clinic, Rochester, Minnesota, 55905 USA.
  • Mirchia K; Departments of Immunology, Mayo Clinic, Rochester, Minnesota, 55905 USA.
  • Sauer BM; Departments of Neurology, Mayo Clinic, Rochester, Minnesota, 55905 USA.
  • McGovern RM; Departments of Neurology, Mayo Clinic, Rochester, Minnesota, 55905 USA.
  • Reid JM; Neurobiology of Disease PhD program, Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, 55905 USA.
  • Buenz EJ; Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, Minnesota, 55905 USA.
Sci Rep ; 6: 28699, 2016 06 27.
Article em En | MEDLINE | ID: mdl-27345730
Neurologic complications associated with viral encephalitis, including seizures and cognitive impairment, are a global health issue, especially in children. We previously showed that hippocampal injury during acute picornavirus infection in mice is associated with calpain activation and is the result of neuronal death triggered by brain-infiltrating inflammatory monocytes. We therefore hypothesized that treatment with a calpain inhibitor would protect neurons from immune-mediated bystander injury. C57BL/6J mice infected with the Daniel's strain of Theiler's murine encephalomyelitis virus were treated with the FDA-approved drug ritonavir using a dosing regimen that resulted in plasma concentrations within the therapeutic range for calpain inhibition. Ritonavir treatment significantly reduced calpain activity in the hippocampus, protected hippocampal neurons from death, preserved cognitive performance, and suppressed seizure escalation, even when therapy was initiated 36 hours after disease onset. Calpain inhibition by ritonavir may be a powerful tool for preserving neurons and cognitive function and preventing neural circuit dysregulation in humans with neuroinflammatory disorders.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Calpaína / Inibidores de Cisteína Proteinase / Theilovirus / Infecções por Cardiovirus / Fármacos Neuroprotetores / Ritonavir Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Calpaína / Inibidores de Cisteína Proteinase / Theilovirus / Infecções por Cardiovirus / Fármacos Neuroprotetores / Ritonavir Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article