title: Attenuating Ischemic Disruption of K+Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment.
abstract: Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K+homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K+homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K+homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K+homeostasis in the neonatal cortex. Since maintaining cellular K+homeostasis and inhibiting excessive K+fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K+homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.
authors.affiliation: Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, 77030, USA.
authors.forename: Dongman
authors.initials: D
authors.lastname: Chao
authors.affiliation: Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, 77030, USA.
authors.forename: Qinyu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.affiliation: Shanghai Research Center for Acupuncture and Meridians, Guoshoujing Rd 199, Shanghai, 201203, People's Republic of China.|Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, 77030, USA. Ying.Xia@uth.tmc.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
mesh_terms: D015670:Acupuncture Therapy; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000172:deficiency; D006706:Homeostasis; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000628:therapy*; D010100:Oxygen; D011188:Potassium / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*
chemical_list: D017465:Receptors, Opioid, delta; D005947:Glucose; D011188:Potassium; D010100:Oxygen
keywords: Acupuncture; Cortex; K+ homeostasis; Neonatal hypoxia-ischemia; Neuroprotection; δ-opioid receptor