Association of medullary reticular formation ventral part with spasticity in mice suffering from photothrombotic stroke
Shogo Isumi,
Daiki Futamura,
Takuto Hanasaki,
Yukito Sako,
Shotaro Miyata,
Hirohito Kan,
Yumika Suzuki,
Naoki Hasegawa,
Hajime Mushiake,
Satoshi Kametaka,
Yasushi Uchiyama,
Makoto Osanai,
Sachiko Lee-Hotta
Affiliations
Shogo Isumi
Graduate School of Medicine, Nagoya University, Nagoya, Japan
Daiki Futamura
Graduate School of Medicine, Nagoya University, Nagoya, Japan
Takuto Hanasaki
Graduate School of Medicine, Nagoya University, Nagoya, Japan
Yukito Sako
Graduate School of Medicine, Nagoya University, Nagoya, Japan
Shotaro Miyata
Graduate School of Medicine, Nagoya University, Nagoya, Japan
Hirohito Kan
Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Japan
Yumika Suzuki
Graduate School of Medicine, Nagoya University, Nagoya, Japan
Naoki Hasegawa
Department of Radiological Imaging and Informatics, School of Medicine, Tohoku University, Sendai, Japan
Hajime Mushiake
Department of Physiology, School of Medicine, Tohoku University, Sendai, Japan
Satoshi Kametaka
Division of Biofunctional Sciences, Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Japan
Yasushi Uchiyama
Division of Creative Physical Therapy, Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, Aichi 461-8673, Japan
Makoto Osanai
Department of Physiology, School of Medicine, Tohoku University, Sendai, Japan; Laboratory for Physiological Functional Imaging, Department of Medical Physics and Engineering, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Japan
Sachiko Lee-Hotta
Division of Creative Physical Therapy, Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, Aichi 461-8673, Japan; Corresponding author.
Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions.Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.
