Abstract
Objective
To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways.
Methods
Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot.
Results
Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05).
Conclusions
Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.
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Liu BH, Guo Y and Xu ZF participated in the design of the study. Liu BH, Zhou D, Guo TT, Tang HL and Chen XY carried out all of the experiments. Xu ZF and Zhang S performed the statistical analysis. Liu BH, Xu ZF, Gong YN and Guo YM drafted the manuscript and revised it. All authors have read and approved the final manuscript.
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The authors declare that they have no competing interests.
Supported by the National Natural Science Foundation of China (No. 81873369, 81704146, 81273868 and 81330088), the Tianjin Municipal Bureau of Labor and Social Security (No. 2018015)
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Liu, Bh., Zhou, D., Guo, Y. et al. Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway. Chin. J. Integr. Med. 27, 291–299 (2021). https://doi.org/10.1007/s11655-021-3326-5
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DOI: https://doi.org/10.1007/s11655-021-3326-5