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Microglial depletion under thalamic hemorrhage ameliorates mechanical allodynia and suppresses aberrant axonal sprouting
Shin-ichiro Hiraga, … , Mariko Nishibe, Toshihide Yamashita
Shin-ichiro Hiraga, … , Mariko Nishibe, Toshihide Yamashita
Published February 13, 2020
Citation Information: JCI Insight. 2020;5(3):e131801. https://doi.org/10.1172/jci.insight.131801.
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Research Article Inflammation Neuroscience

Microglial depletion under thalamic hemorrhage ameliorates mechanical allodynia and suppresses aberrant axonal sprouting

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Abstract

Central poststroke pain (CPSP) is one of the neuropathic pain syndromes that can occur following stroke involving the somatosensory system. However, the underlying mechanism of CPSP remains largely unknown. Here, we established a CPSP mouse model by inducing a focal hemorrhage in the thalamic ventrobasal complex and confirmed the development of mechanical allodynia. In this model, microglial activation was observed in the somatosensory cortex, as well as in the injured thalamus. By using a CSF1 receptor inhibitor, we showed that microglial depletion effectively prevented allodynia development in our CPSP model. In the critical phase of allodynia development, c-fos–positive neurons increased in the somatosensory cortex, accompanied by ectopic axonal sprouting of the thalamocortical projection. Furthermore, microglial ablation attenuated both neuronal hyperactivity in the somatosensory cortex and circuit reorganization. These findings suggest that microglia play a crucial role in the development of CPSP pathophysiology by promoting sensory circuit reorganization.

Authors

Shin-ichiro Hiraga, Takahide Itokazu, Maki Hoshiko, Hironobu Takaya, Mariko Nishibe, Toshihide Yamashita

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Figure 1

Thalamic hemorrhage induces mechanical allodynia without affecting motor functions.

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Thalamic hemorrhage induces mechanical allodynia without affecting motor...
(A) Schema of the thalamic hemorrhage (TH) induction method. VPL, ventral posterolateral nucleus; AP, anterior-posterior; ML, medial-lateral. (B) Anatomy of our injection target, the VPL, and its surrounding area. The ventrobasal complex (VB) consists of the VPL and ventral posteromedial nucleus (VPM). (C) Representative image of the Nissl-stained tissue sections. Scale bar: 1 mm. (D) An experimental design showing the time-course of TH induction and behavioral tests. (E) The 50% withdrawal threshold of the contralesional hind paw was significantly decreased 5 days after TH induction and persisted throughout the testing period (*P < 0.01, 2-way repeated measures ANOVA followed by Sidak’s multiple comparisons test). (F–H) No motor deficit was observed in TH mice. (F) The neurologic grade (P > 0.05, group effect by 2-way repeated measures ANOVA). (G) The ladder walk test (P > 0.05, group effect by 2-way repeated measures ANOVA). (H) The rotarod assessment (P > 0.05, group effect by 2-way repeated measures ANOVA). (I and J) There was no significant difference in the lesion area quantified on days 4, 7, and 21 after TH (P > 0.05, group effect by 1-way repeated measures ANOVA). Red outlines in images represent the edges of lesions. Scale bar: 1 mm.

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