A mouse model of weight-drop closed head injury:emphasis on cognitive and neurological deficiency

Traumatic brain injury（TBI） is a leading cause of death and disability in individuals worldwide.Producing a clinically relevant TBI model in small-sized animals remains fairly challenging.For good screening of potential therapeutics,which are effective in the treatment of TBI,animal models of TBI should be established and standardized.In this study,we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model.We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice.Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury.Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI.

Electro-acupuncture at Conception and Governor vessels and transplantation of umbilical cord bloodderived mesenchymal stem cells for treating cerebral ischemia/reperfusion injury

Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/ reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch- emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot- ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.

Mechanisms of electroacupuncture effects on acute cerebral ischemia/reperfusion injury:possible association with upregulation of transforming growth factor beta 1

Electroacupuncture at the head acupoints Baihui（GV20） and Shuigou（GV26） improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1（TGF-β1）.To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a “dispersedense” wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.

Effect of acupuncture on cerebral hematoma volume and HO-1 expression in rats with acute cerebral hemorrhage

Objective:To explore the effect of acupuncture on the expression of heme oxygenase-1 in rats with acute cerebral hemorrhage.Methods:108 Wistar male rats were randomly divided into sham operation group,model group,and acupuncture combined with model group(referred to as acupuncture group).Each group was divided into 3 subgroups according to 1d,3d and 7d,with 6 rats in each subgroup.The rat model of cerebral hemorrhage was established by autologous blood injection.Acupuncture was given at Baihui(GU20)and Qubin(GB7).Separately,at the 1st,3rd and 7th day,modified neurological severity score was used to evaluate the neurological function of rats,HE staining was used to measure the volume of cerebral hematoma and western blot was used to detect the expression of heme oxygenase-1 protein in cerebral hematoma tissue.Results:Compared with the model group,at each time point,the modified neurological severity score of the acupuncture group was significantly reduced(P<0.01);at the two time points of 3rd and 7th day,the cerebral hematoma volume of the acupuncture group was significantly reduced(P<0.05)and the expression of heme oxygenase-1 protein in brain tissue was significantly increased(P<0.05).Conclusion:Acupuncture may promote the expression of heme oxygenase-1 protein,reduce the volume of hematoma and the score of neurological deficit in rats with intracerebral hemorrhage,improve the performance of neurological deficit,and play a role in brain protection.

Neuroprotective effect of AG490 in experimental traumatic brain injury of rats

Background Traumatic brain injury （TBI） is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI. Methods Sprague Dawley rats （n=240） were randomly divided into a sham operation group, TBl＋saline group and TBI＋AG490 （JAK/STAT inhibitor） group, Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score （NSS） was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry. Results In both the TBl＋saline group and the TBI＋AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the pedod investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the Level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI＋AG490 group. Conclusion Inhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.