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.
ABSTRACT
Objective To investigate the effect of hand twelve Jing-Well points bloodletting on blood-brain barrier (BBB) permeability in the early stage of focal cerebral ischemic injury in rats with permanent middle cerebral artery occlusion (pMCAO). Method Male Wister rats were randomized into sham operation, model and bloodletting groups. A model of middle cerebral artery occlusion was made by Longa's method. 2%Evans blue (EB) was injected into the caudal vein at three time points:5, 24 and 72 hrs after model making. EB exudation amount was assessed by measurement of EB absorbance in brain tissue to observe BBB permeability. Result Cerebral EB exudation amount was significantly higher in the model group of rats than in the sham operation group (P<0.01) and significantly lower in the bloodletting group than in the model group (P<0.01). Conclusion Hand twelve Jing-Well points bloodletting can reduce blood-brain barrier permeability in pMCAO rats. Its effect is highly significant at 24 and 72 hrs after ischemia.