| Objective:To establish rat transient and permanent cerebral ischemia model and to give them vagus nerve stimulation, hyperbaric oxygen treatment and combined treatment of both. After the intervention, we observed their neurobehavioral score, infarct volume, brain swelling, brain histopathology and the expression of inflammatory cytokines in brain to detect whether combination therapy with vagus nerve stimulation and hyperbaric oxygen treatment have more significant neuroprotective effects, and to explore its potential mechanisms.Methods:According to the different cerebral ischemia time, we setted transient cerebral ischemia group (T-MCAO group) and permanent cerebral ischemia group (P-MCAO group). And then everyone of them was divided further into four sub-groups respectively according to the different interventions, which included combined treatment group (T-VNS+HBO group/P-VNS+HBO group), which were given vagus nerve stimulation and hyperbaric oxygen therapy, vagus nerve stimulation group (T-VNS group/P-VNS group), which were given simply vagus nerve stimulation, hyperbaric oxygen group (T-HBO group/P-HBO group), which were given simply hyperbaric oxygen therapy, and control group (T-Con group/P-Con group), which were not given any treatment.176male Sprague-Dawley rats were randomly assigned to each subgroup,22/subgroups. Transient Cerebral ischemia model of T-MCAO group was produced by intra-arterial filament occlusion of the right MCA (Middle Cerebral Artery) for2hours, and then reperfusion was achieved by withdrawal of the filament. Permanent Cerebral ischemia model of P-MCAO group was produced by intra-arterial filament occlusion of the right MCA, but no reperfusion was achieved. After succeful modeling, everyone of different subgroups were given appropriate therapic methods respectively. At24hours after ischemia, we observed neurobehavioral score, infarct volume, brain swelling, brain histopathology and the expression of inflammatory cytokines in brain.Results:There were some results of pairwise comparison for4subgroups in T-MCAO group to be shown.①Compared with T-VNS group, T-HBO group and T-Con group, T-VNS+HBO group’s neurobehavioral score, infarct volume were significantly improved (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of brain pro inflammatory cytokine TNF-a and IL-1β were significantly lower (P<0.05), the expression levels of brain antiinflammatory cytokines IL-10were significantly increased (P<0.05). However, its degree of brain swelling were not more significantly improved than T-VNS group and T-HBO group’s but T-Con group’s.②Compared with T-Con group, T-VNS and T-HBO group’s neurobehavioral score, infarct volume were significantly improved (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of brain proinflammatory cytokine TNF-a and IL-1β were significantly lower (P<0.05), the expression levels of brain antiinflammatory cytokines IL-10were significantly increased (P<0.05). However, both of their degree of brain swelling were not more significantly improved than T-Con group’s.③There was not any significant difference between T-VNS group and T-HBO group ’s all indicators (P>0.05), which included neurobehavioral score, infarct volume, brain swelling and the expression of inflammatory cytokines in brain. And the microscopic histopathology performance of them were similar to each other.There were some results of pairwise comparison for4subgroups in P-MCAO group to be shown.①Compared with P-VNS group, P-HBO group and P-Con group, P-VNS+HBO group’s neurobehavioral score, infarct volume were significantly improved (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of brain proinflammatory cytokine TNF-a and IL-1β were significantly lower (P<0.05), the expression levels of brain antiinflammatory cytokines IL-10were significantly increased (P<0.05). However, its degree of brain swelling were not more significantly improved than P-VNS group and P-HBO group’s but P-Con group’s.②Compared with P-Con group, P-VNS group and P-HBO group’s neurobehavioral score, infarct volume were significantly improved (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of brain proinflammatory cytokine TNF-a and IL-1β were significantly lower (P<0.05), the expression levels of brain antiinflammatory cytokines IL-10were significantly increased (P<0.05). However, both of their degree of brain swelling were not more significantly improved than P-Con group’s.③There was not any significant difference between P-VNS group and P-HBO group ’s all indicators (P>0.05), which included neurobehavioral score, infarct volume, brain swelling and the expression of inflammatory cytokines in brain. And the microscopic histopathology performance of them were similar to each other.There were some results of comparison between T-MCAO group and P-MCAO group’s subgroups, which were given the same treatment.①Compared with the P-VNS+HBO group, T-VNS+HBO group’s neurobehavioral scores were significantly increased (P<0.05), and infarct volume was significantly reduced (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of proinflammatory cytokine in brain were significantly decreased (P<0.05), and the expression levels of antiinflammatory cytokines were significantly increased (P <0.05), but brain swelling was not improved,②Compared with the P-VNS group, T-VNS group’s neurobehavioral scores were significantly increased (P<0.05), and infarct volume was significantly reduced (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of proinflammatory cytokine in brain were significantly decreased (P<0.05), and the expression levels of antiinflammatory cytokines were significantly increased (P<0.05), but brain swelling was not improved.③Compared with the P-HBO group, T-HBO group’s neurobehavioral scores were significantly increased (P<0.05), and infarct volume was significantly reduced (P<0.05), and necrosis, and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of proinflammatory cytokine in brain were significantly decreased (P<0.05), and the expression levels of antiinflammatory cytokines were significantly increased (P<0.05), but brain swelling was not improved.④Compared with the P-Con group, T-Con group’s neurobehavioral scores were significantly increased (P<0.05), and infarct volume was significantly reduced (P<0.05), and necrosis and tissue edema were significantly reduced in ischemic lesion marginal-zone under the microscope, and the expression levels of proinflammatory cytokine in brain were significantly decreased (P<0.05), and the expression levels of antiinflammatory cytokines were significantly increased (P<0.05), but brain swelling was not improved.Conclusions:Both Vagus nerve stimulation and hyperbaric oxygen therapy can regulate the inflammatory response in order to produce neuroprotective effect for cerebral ischemic injury in rats, and the effect of regulation and nerve-protection on transient cerebral ischemia model are greater than permanent cerebral ischemia model. When Combined Vagus nerve stimulation with hyperbaric oxygen therapy to treat cerebral ischmia, it have more significant effects of neuroprotective and inflammation regulation, and the effects on transient cerebral ischemia model are also greater than permanent cerebral ischemia model. |
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