• Child Brain Project

Child Brain Project

Translational research for child brain

Project Leader Hiroshi Sakuma

Project Leader
Hiroshi Sakuma

Research Summary

Our research focuses on autoimmune and inflammatory neurological diseases (AINDs) in childhood. They are significant social burden because of poor prognosis and high mortality. We have established a sustainable platform (a multicenter registry of patients and sample repository) for a prospective cohort studies on AINDs based on nationwide collaborative study. We perform multi-omics analysis of biomarkers including inflammatory mediators, microRNAs, and metabolites. This multifaceted approach using high-throughput methods enables us to explore novel molecular targets associated with AINDs.

Recent studies have highlighted the importance of glial cells in the pathogenesis of AINDs. Our transgenic animal models are expected to shed new light on how gilal cells contribute to the pathomechanisms of AINDs by regulating brain metabolism and inflammation, and also provide a rationale for a novel therapeutic strategy.

Our main research areas include:

  1. Pathomechanisms of virus-associated acute encephalopathies
  2. The role of inflammation in febrile infection-related epilepsy syndrome
  3. Autoimmune encephalitis and acquired demyelinating syndromes
  4. Autoantibodies associated with neurological diseases
  5. New biomarkers for pediatric immune-mediated neurological diseases
Figure Pathomechanisms of inflammatory and autoimmune neurological diseases
Multiple sclerosis has been regarded as CD4 T-cell mediated disease, in which autoreactive T cells are activated, proliferate, migrate into brain, and cause myelin damage. Autoimmune encephalitis is caused by autoantibodies against neuronal surface antigens, produced by plasma cells in both periphery and central nervous system. Although the pathogenesis of virus-associated encephalopathy has not been fully elucidated, pro-inflammatory cytokines and chemokines are highly increased in biofluids, suggesting cytokine-mediated mechanisms.

Selected Publications

  • Nosadini M et al. (2021) “Use and safety of immunotherapeutic management of N-methyl-d-aspartate receptor antibody encephalitis: a meta-analysis.” JAMA Neurol. 78:1333-1344.
  • Nosadini M et al. (2021) International consensus recommendations for the treatment of pediatric NMDAR antibody encephalitis. Neurol Neuroimmunol Neuroinflamm. 8:e1052.
  • Nishida H et al. (2021) “Evaluation of the diagnostic criteria for anti-NMDA receptor encephalitis in Japanese children.” Neurology. 50:e2070-e2077.
  • Horino A, et al. (2021) “Intrathecal dexamethasone therapy for febrile infection-related epilepsy syndrome.” Ann. Clin. Transl. Neurol. 8:645-655.
  • Suzuki T, et al. (2020) “Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor.” Eur. J. Immunol. 50:205-219.
  • Sakuma H, et al. (2015) “Intrathecal overproduction of proinflammatory cytokines and chemokines in febrile infection-related refractory status epilepticus.” J. Neurol. Neurosurg. Psychiatr. 86:820-822