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Child Brain Project

A Consortium to Overcome Childhood Brain Diseases

Project Leader Hiroshi Sakuma

Project Leader
Hiroshi Sakuma

Backgrounds

Achievements in 2024

Chronic stressful environments are known to induce depressive and anxiety-like behaviors in mice. We demonstrated that chronic stress conditions induce depressive and anxiety-like behaviors by decreasing the expression of Neuritin, which in turn suppresses the activation of FGF signaling and reduces axonal branching of serotonergic neurons.

In clinical research, as a result of our multi-institutional clinical studies, we developed a diagnostic prediction score for NMDAR encephalitis in children and clarified the clinical characteristics of SARS-CoV-2 associated encephalopathy. We also led an international collaborative study on virus-related acute encephalopathy that proposed the new concept of infection-triggered encephalopathy syndrome (ITES) and published consensus guidelines for it.

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.

Publications

Papers in 2024

  • Shimada T, et al. (2024) “ Neuritin controls axonal branching in serotonin neurons: A possible mediator involved in the regulation of depressive and anxiety behaviors via FGF signaling. ” J Neurosci. 44: 1-17.
  • Kasai M, et al. (2024) “ Clinical characteristics of SARS-CoV-2-associated encephalopathy in children: Nationwide epidemiological study. ” J Neurol Sci. 457:122867.
  • Sakuma H, et al. (2024) “ International consensus definitions for infection-triggered encepha- lopathy syndromes. ” Dev Med Child Neurol. doi: 10.1111/dmcn.16067.

Key papers

  • 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.
  • Horino A, et al. (2021) “Intrathecal dexamethasone therapy for febrile infection-related epilepsy syndrome.” Ann. Clin. Transl. Neurol, 8:645-655.
  • Nishida H et al. (2021) “Evaluation of the diagnostic criteria for anti-NMDA receptor encephalitis in Japanese children.”Neurology. 50:e2070-e2077.