Abstract
Orexin is an important neuropeptide that stimulates cortical activation and arousal and is involved in the regulation of wakefulness and arousal. Our previous meta-analysis showed that acupuncture fared well in the treatment of TBI-induced DOC in which “shuigou (DU 26)” was the most important and frequent point targeted. In the present study, we investigated whether electroacupuncture (EA) promotes TBI-induced unconsciousness wakefulness via orexin pathway. A TBI rat model was established using a control cortical impact (CCI) model. In the stimulated group, TBI rats received EA (15 Hz, 1.0 mA, 15 min). In the antagonist group, TBI rats were intraperitoneally injected with the orexin receptor 1 (OX1R) antagonist SB334867 and received EA. Unconsciousness time was observed in each group after TBI, and electrocorticography (ECoG) was applied to detect rats' EEG activity. Immunohistochemistry, enzyme-linked immunosorbent assay, and western blot were used to assess the levels of orexin-1(OX1) and OX1R expression in the mPFC. We show that duration of unconsciousness and the ratio of delta power in ECoG in the EA group were significantly reduced compared with those in the TBI group. EA could increase OX1 and OX1R expression in the mPFC and reduced the loss of orexin-producing neurons in LHA. However, all the efficacy of EA was blocked by the OX1R antagonist SB334867. Our findings suggest that EA promotes the recovery of consciousness of TBI-induced unconscious rats via upregulation of OX1and OX1R expression in mPFC.
Highlights
Traumatic brain injury (TBI) is a global public health problem and a leading cause of death and disability [1]
Recovery of consciousness is closely associated with recovery in other functional domains, and the duration of disorder of consciousness (DOC) is an important prognostic factor in patients with TBI [13, 14]. e treatment for TBI-induced unconsciousness includes drug therapies [15], deep brain stimulation (DBS) [16, 17], hyperbaric oxygenation [18], and nerve electrical stimulation [19]
We further explored the expression of OX1 and OX1R in the medial prefrontal cortex (PFC) and the presence of orexin-positive neurons in the lateral hypothalamus (LHA)
Summary
Traumatic brain injury (TBI) is a global public health problem and a leading cause of death and disability [1]. With the recent rapid development of intensive care technology and emergency medicine, the survival of patients with TBI has significantly improved [9]. These individuals experience varying degrees of disorder of consciousness (DOC), which seriously affects their ability to perform activities of daily living and reduces their quality of life [10,11,12]. In China, acupuncture has been used for centuries to promote recovery from DOC, considered to increase the supply of blood and oxygen to the traumatized area of the brain [21] and neuronal excitability [22, 23]. We further explored the expression of OX1 and OX1R in the medial PFC (mPFC) and the presence of orexin-positive neurons in the LHA
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