Association of medullary reticular formation ventral part with spasticity in mice suffering from photothrombotic stroke

Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, while spastic symptoms, such as involuntary muscle contraction in the hands and fingers, severely restrict skilled hand movements. However, the underlying brain arc mechanisms remain unknown. Here, we demonstrated that neuronal activity increases within the contralesional brainstem nucleus medullary reticular formation (MdV) at the acute post-stroke phase, and the increase in neuronal activity markedly appears by electrostimulation for spasticity induction. Interestingly, ascending electrostimulation signals inhibited the ipsilateral MdV activity. Moreover, in the acute phase with spasticity, the GluA1 density at synapses in MdV neurons was significantly increased, and the ratio of AMPAR subunits transitioned from GluA1 to GluA2 at 2 weeks post-stroke. Thus, this homeostatic plasticity is a mechanism of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity symptoms at the acute post-stroke phase.

脑卒中可通过脊髓内的牵张反射过度兴奋引发痉挛，而手部及手指的不自主肌肉收缩等痉挛症状，会严重限制精细手部运动功能。然而，其背后的脑环路机制仍未明确。本研究证实，脑卒中急性期，对侧延髓网状核（medullary reticular formation, MdV）内的神经元活动会出现升高，且该神经元活动的增加会在诱发痉挛的电刺激下显著显现。值得注意的是，上行电刺激信号会抑制同侧MdV的神经元活动。此外，在伴有痉挛的脑卒中急性期，MdV神经元突触的GluA1密度显著升高；而在脑卒中发病2周时，AMPA受体（AMPAR）亚基的组成比例从GluA1向GluA2发生转变。综上，这种稳态可塑性是痉挛的潜在发病机制。本研究结果为脑卒中急性期精细运动受损与痉挛症状之间的关联提供了全新的认识。