Cerebellar Demyelination and Synaptic Impairment-Induced Cerebellar Ataxia in Mice Heatstroke Model

First Author(s)

• 

  KAZUYUKI MIYAMOTO, MD, PhD

  Associate professor
  Showa University
  Tokyo, Japan

  Disclosure information not submitted.

  Slides

Co-Author(s)

• HO

  Hirokazu Ohtaki

  Associate professor
  Department of Anatomy, Showa University School of Medicine,, United States

  Disclosure information not submitted.
• MN

  Motoyasu Nakamura

  Assistant professor
  Department of Emergency, Critical care and Disaster medicine, Showa University School of Medicine, United States

  Disclosure information not submitted.
• KS

  Keisuke Suzuki

  Assistant professor
  Department of Emergency, Critical care and Disaster medicine, Showa University School of Medicine, United States

  Disclosure information not submitted.
• HY

  Hiroki Yamaga

  Assistant professor
  Department of Emergency, Critical care and Disaster medicine, Showa University School of Medicine, United States

  Disclosure information not submitted.
• KY

  Kaoru Yanagisawa

  Assistant professor
  Department of Emergency, Critical care and Disaster medicine, Showa University School of Medicine, United States

  Disclosure information not submitted.
• AM

  Atsuo Maeda

  Lecturer
  Showa University Fujigaoka Hospital, United States

  Disclosure information not submitted.
• MY

  Masaharu Yagi

  Associate professor
  Department of Emergency, Critical care and Disaster medicine, Showa University School of Medicine, United States

  Disclosure information not submitted.
• KH

  Kazuho Honda

  Professor
  Department of Anatomy, Showa University School of Medicine, United States

  Disclosure information not submitted.
• kD

  kenji Dohi, N/A

  Professor
  Showa University
  Tokyo, Japan

  Disclosure information not submitted.

Title: Cerebellar ataxia was appeared 3 weeks post heat exposure by the synaptic impairment at cerebellum

Introduction:
Brain is extremely sensitive to hyperthermia. Consciousness disturbance is inevitable in heatstroke patient. Such as consciousness disturbance improves once the core body temperature falls below the critical level in acute phase. However, there are cases that neurological sequelae remain after heatstroke that interrupts the patients getting the back to social life. Previously studies have reported that brain injury after heatstroke strong appeared in the cerebellum as its structures were vulnerable to heat. Interestingly, there are several reports cerebellar ataxia appeared several weeks post heatstroke. Thought, the mechanism of this delayed cerebellar ataxia after heatstroke is not well understood. We focused on the delayed cerebellar ataxia after heatstroke using the rodent heatstroke model.

Results:
Male C57BL/6J mice were subjected to heat exposure for 60 min as a heatstroke group (HS). The animals which were not exposed to heat as a control (Ct). Behavioral test (Rota-rod) was performed 1, 3, 5, 7 and 9 weeks post heat exposure and running time was compared between Ct and HS group. Motor coordination disorder in HS group significantly appeared 3 weeks post heat exposure and gradually improved to some extent over time. Then, another aligned ages two group (Ct, HS) were prepared and brains were removed 1, 3 and 9 weeks post heat exposure. Klüver-Barrera (KB) staining was performed to evaluate the demyelination at cerebellum and corpus callosum. Immunostaining of Calbindin was performed to semi-quantify of the Purkinje cells. Demyelination was detected 1, 3 weeks and the number of Purkinje cell significantly decreased 1,3 and 9 weeks post heat exposure. Moreover, we performed immunostaining of Synaptophysin and Postsynaptic density-95 (PSD-95) to evaluate the pre and post synapses around Purkinje cells. The expression of Synaptophysine and PSD-95 around Purkinje cells were weakest in 3 weeks post heat exposure and improved over the time.

Conclusion:
Delayed cerebellar ataxia in heatstroke appeared from 3 week and recovered to some extent over time. Our results suggested that permanent Purkinje cells loss, transient demyelination and synaptic impairment at cerebellum might correlated with delayed cerebellar ataxia of heatstroke.