Research Publications Spotlight

Complementary Therapies in Clinical Practice
A Close Look at an Integrative Treatment Package for Bell’s Palsy in Korea
Lee SMK, Lee S, Park JH, Park JJ, Lee, S


Objective: To provide an overview of the integrative treatment package for Bell’s palsy provided at Kyung Hee University Korean Medicine Hospital (KHU KMH).

Summary: The Facial Palsy Center at KHU KMH has been providing integrative treatment for Bell’s palsy patients during the past three decades. Within 72 h of symptom onset, corticosteroids are recommended but complementary treatment including acupuncture and herbal medicine can be used to help suppress inflammation and nerve degeneration. If patients suffer from postauricular pain, pharmacopuncture and cupping is utilized. During the subacute or chronic periods, different acupuncture types are selected accordingly, and herbal medicine and moxibustion helps to improve immune functions and relieve accessory symptoms. Qigong programs are also provided to help relieve facial tension and paralysis.

Conclusions: Although rigorous research is warranted, with limited treatment options, we highly suggest that it is worth applying integrative medicine to Bell’s palsy patients.

Journal of Women’s Health
Sex and Age Interactions and Differences in Outcomes After Intracerebral Hemorrhage
James ML, Cox M, Xian Y, Smith EE, Bhatt DL, Schulte PJ, Hernandez A, Fonarow GC, Schwamm LH


Background: Compared to ischemic stroke, sex differences in response to intracerebral hemorrhage (ICH) are largely unexplored, and their potential interactions with patient age have not been examined. This study hypothesized that risk for poor outcome is greater in women with increasing age.

Methods and Results: The Get With The Guidelines®–Stroke database was used to assess differences between men and women with ICH. Data from 192,826 ICH patients admitted from January 1, 2009 through March 31, 2014 to 1,728 fully participating sites were analyzed using logistic regression to test interactions between age/sex and outcome.

Results: In the total study population, 48.9% were women (median age 75; male median age 67). On admission, women over 65 years were less likely to have atrial fibrillation or dyslipidemia, or use antiplatelet therapy or cholesterol reducers, but more likely to suffer worse neurological deficit than men over 65. As age increased, odds of in-hospital mortality increased in both men and women, although the relationship was stronger in men. Odds of combined mortality and discharge to hospice were similar in men and women with increasing age, but odds for discharge to home and independent ambulation at discharge decreased more in women with increasing age.

Conclusions: After adjusting for covariates, modest sex differences in early outcomes after ICH were linked to age. While statistically significant, detected interactions should be considered in context. Future study may examine whether sex-based interactions represent biologic or treatment differences, unmeasured covariates, or some combination thereof.

Neuron-Specific SUMO Knockdown Suppresses Global Gene Expression Response and Worsens Functional Outcome After Transient Forebrain Ischemia in Mice
Zhang L, Liu X, Sheng H, Liu S, Li Y, Zhao JQ, Warner DS, Paschen W, Yang W


Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neurons, a neuroprotective response to ischemia. It is also known from cell culture studies that SUMOylation modulates gene expression. However, it remains unknown how SUMOylation regulates neuronal gene expression in vivo, in the physiologic state and after ischemia, and modulates post-ischemic recovery of neurologic function. To address these important questions, we used a SUMO1-3 knockdown (SUMO-KD) mouse in which a Thy-1 promoter drives expression of 3 distinct microRNAs against SUMO1-3 to silence SUMO expression specifically in neurons. Wild-type and SUMO-KD mice were subjected to transient forebrain ischemia. Microarray analysis was performed in hippocampal CA1 samples, and neurologic function was evaluated. SUMOylation had opposite effects on neuronal gene expression before and after ischemia. In the physiological state, most genes regulated by SUMOylation were up-regulated in SUMO-KD compared to wild-type mice. Brain ischemia/reperfusion significantly modulated the expression levels of more than 400 genes in wild-type mice, with a majority of those genes upregulated. The extent of this post-ischemic transcriptome change was suppressed in SUMO-KD mice. Moreover, SUMO-KD mice exhibited significantly worse functional outcome. This suggests that suppression of global gene expression response in post-ischemic brain due to SUMO knockdown has a negative effect on post-ischemic neurologic function. Together, our data provide a basis for future studies to mechanistically link SUMOylation to neurologic function in health and disease.

Brain Research
Antiepileptic Drugs Prevent Seizures in Hyperbaric Oxygen: A Novel Model of Epileptiform Activity
Demchenko IT, Yu Zhilyaev S, Moskvin AN, Krivchenko AI, Piantadosi CA, Allen BW


Breathing oxygen at sufficiently elevated pressures can trigger epileptiform seizures. Therefore, we tested the hypothesis that pre-treatment with FDA-approved antiepileptic drugs could prevent seizure onset in hyperoxia at 5 atmospheres absolute. We selected drugs from two putative functional categories, Na+-channel antagonists and GABA enhancers, each administered intraperitoneally at four doses in separate groups of C57BL/6 mice. The drugs varied in efficacy at the doses used. Of the five tested Na+-channel antagonists, carbamazepine and lamotrigine more than tripled seizure latency compared to values seen in vehicle controls. Primidone, zonisamide and oxcarbazepine were less effective. Of the four GABA reuptake inhibitors, tiagabine and vigabatrin also increased seizure latency by more than three times control values; valproic acid was less effective, and the GABA synthesis promoter gabapentin was intermediate in effectiveness. We infer that Na+-channel function and GABA neurotransmission may be critical targets in the pathophysiology of CNS O2 toxicity. Because these essential components of neuronal excitation and inhibition are also implicated in the pathogenesis of other seizure disorders, including generalized epilepsy, we propose that, at some level, common pathways are involved in these pathologies, although the initiating insults differ. Furthermore, hyperoxic exposures are not known to cause the spontaneously-recurring seizures that characterize true clinical epilepsy. Nonetheless, experimental studies of hyperbaric oxygen toxicity could provide new insights into molecular mechanisms of seizure disorders of various etiologies. In addition, the neuropathology of hyperbaric oxygen is particularly relevant to the hypothesis held by some investigators that oxidative stress is an etiological factor in clinical epilepsies.