Abstract
The induction of a coma by traumatic brain injury (TBI) is a crucial factor for poor clinical prognoses. We report that acupuncture at the hand 12 Jing-Well points (HTWP) improved consciousness and neurologic function in TBI rats. Gene chip analyses showed that HTWP acupuncture mostly activated genes modulating neuronal projections (P2rx7, P2rx3, Trpv1, Tacr1, and Cacna1d), protein secretion (Exoc1, Exoc3l1, Fgb, and Fgr), and dopamine (DA) receptor D3 (Drd3) in the ventral periaqueductal gray (vPAG), among which the expression rate of P2rx7 was the most obviously increased. Acupuncture also increased the expression and excitability of DA and P2RX7 neurons, and the DA neurons expressed P2RX7, P2RX3, and TRPV1 in the vPAG. Intracerebroventricular administration of P2RX7, P2RX3, or TRPV1 antagonists blocked acupuncture-induced consciousness, and the subsequent injection of a P2RX7 antagonist into the vPAG nucleus also inhibited this effect. Our findings provide evidence that acupuncture alleviates TBI-induced comas via DA neurons expressing P2RX7 in the vPAG, so as to reveal the cellular and molecular mechanisms of the improvement of TBI clinical outcomes by HTWP acupuncture.
Highlights
Traumatic brain injury (TBI) is a major challenge for modern medicine; it affects about 55 million people worldwide, with over 27 million new cases reported in 2016 (GBD 2016 Traumatic Brain Injury Spinal Cord Injury Collaborators, 2019)
hand twelve Jing-Well points (HTWP) acupuncture was effective at reducing the coma duration to 112.50 ± 4.67 min (P < 0.01), and FTPW acupuncture reduced it to an average of 122.67 ± 7.45 min (P < 0.05) compared with TBI, but there was no statistical difference between the two groups
foot twelve Jing-Well points (FTWP) acupuncture failed to improve the neurological score. These results indicate that HTWP acupuncture significantly improved consciousness and neurologic function in TBI rats through a specific mechanism compared with FTWP acupuncture
Summary
Traumatic brain injury (TBI) is a major challenge for modern medicine; it affects about 55 million people worldwide, with over 27 million new cases reported in 2016 (GBD 2016 Traumatic Brain Injury Spinal Cord Injury Collaborators, 2019). Despite multiple efforts to develop effective treatments, there are still no first-line responder therapeutic strategies to ameliorate TBI pathogenesis and progression. TBI-induced comas are a key factor in poor clinical prognoses, including death (Hutchinson et al, 2016). The pathophysiological mechanisms that induce a coma include injury of the neuronal circuits of the ascending reticular activating system (ARAS), especially in the pons and mesencephalon (Jang et al, 2019). Neurostimulators are often surgically implanted into the brainstem or spinal cord to induce ARAS stimulation and thereby promote consciousness in comatose patients. There remains a need for safe and practical therapeutic strategies that first responders can apply urgently at the hyperacute stage
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