Surgical Reconsideration of Traumatic Facial Paralysis.

INTRODUCTION: Despite the different pathophysiological mechanisms underlying Bell's palsy, in assessing severe traumatic facial paralysis, many surgeons rely on electrophysiological criteria to determine whether facial nerve exploration is warranted. To assess the value of preoperative electroneurography (ENoG) and the time of surgery, we analyzed data from three tertiary medical centers. MATERIALS AND METHODS: The records of 517 patients with a degenerative ratio (DR) greater than 80% on ENoG were collected, and two groups were defined: group A (90% DR ≤ ENoG) and group B (80% DR ≤ ENoG < 90% DR). The difference in effectiveness of surgery versus conservative treatment was analyzed based on the postoperative outcome determined by the House-Brackmann grading system. The independent-samples t test was used to compare surgery with conservative treatment for each day of surgical exploration. RESULT: In groups A and B, the average recovery time from facial paralysis was better in patients who had undergone surgical exploration than in those who had been treated conservatively. In group A, the difference was significant only for patients who underwent surgery within 8 days. In group B, a significant difference was found for patients who underwent surgery within 16 days but also for surgery performed 20 and 30 days after the onset of facial paralysis. DISCUSSION: In the surgical treatment of facial paralysis, the criteria for trauma patients should be distinguished from those of patients with Bell's palsy. In traumatic facial paralysis, some axons are more vulnerable to external collapse, and the degree of Wallerian degeneration of the peripheral nervous system will vary depending on the type of injury. The results of this study will help to identify those patients with traumatic facial paralysis who should be treated surgically and when they should be treated.

Policy Review and Modeling Analysis of Mitigation Measures for Coronavirus Disease Epidemic Control, Health System, and Disease Burden, South Korea.

We reviewed the timeline of key policies for control of the coronavirus disease epidemic and determined their impact on the epidemic and hospital burden in South Korea. Using a discrete stochastic transmission model, we estimated that multilevel policies, including extensive testing, contact tracing, and quarantine, reduced contact rates by 90% and rapidly decreased the epidemic in Daegu and nationwide during February‒March 2020. Absence of these prompt responses could have resulted in a >10-fold increase in infections, hospitalizations, and deaths by May 15, 2020, relative to the status quo. The model suggests that reallocation of persons who have mild or asymptomatic cases to community treatment centers helped avoid overwhelming hospital capacity and enabled healthcare workers to provide care for more severely and critically ill patients in hospital beds and negative-pressure intensive care units. As small outbreaks continue to occur, contact tracing and maintenance of hospital capacity are needed.

Lessons from a COVID-19 hospital, Republic of Korea.

OBJECTIVE: To document the experiences of converting a general hospital to a coronavirus disease 2019 (COVID-19) designated hospital during an outbreak in Daegu, Republic of Korea. METHODS: The hospital management formed an emergency task force team, whose role was to organize the COVID-19 hospital. The task force used different collaborative channels to redistribute resources and expertise to the hospital. Leading doctors from the departments of infectious diseases, critical care and pulmonology developed standardized guidelines for treatment coherence. Nurses from the infection control team provided regular training on donning and doffing of personal protective equipment and basic safety measures. FINDINGS: Keimyung University Daegu Dongsan hospital became a red zone hospital for COVID-19 patients on 21 February 2020. As of 29 June 2020, 1048 COVID-19 patients had been admitted to the hospital, of which 22 patients died and five patients were still being treated in the recovery ward. A total of 906 health-care personnel worked in the designated hospital, of whom 402 were regular hospital staff and 504 were dispatched health-care workers. Of these health-care workers, only one dispatched nurse acquired COVID-19. On June 15, the hospital management and Daegu city government decided to reconvert the main building to a general hospital for non-COVID-19 patients, while keeping the additional negative pressure rooms available, in case of resurgence of the disease. CONCLUSION: Centralized coordination in frontline hospital operation, staff management, and patient treatment and placement allowed for successful pooling and utilization of medical resources and manpower during the COVID-19 outbreak.

Intensive Care Unit Capacity and Its Associated Risk Factors During the COVID-19 Surge in the Republic of Korea: Analysis Using Nationwide Health Claims Data.

OBJECTIVE: To identify risk factors for intensive care unit (ICU) admission and mechanical ventilator usage among confirmed coronavirus disease (COVID-19) patients and estimate the effects of mitigation efforts on ICU capacity in Korea. PATIENTS AND METHODS: Data on profiles and medical history of all confirmed COVID-19 patients in the past 1 year were extracted from the Korean National Health Insurance System's claims database to assess risk factors for ICU admission and ventilator use. We used a time-series epidemic model to estimate the ICU census in Daegu from the reported hospital data. FINDINGS: Multivariate regression analysis revealed male sex, old age, and residing in Daegu city as significant risk factors for ICU admission. The number of patients requiring ICU admission exceeded the bed capacity across all Daegu hospitals before March 9, 2020, and therefore, critically ill patients were transferred to nearby hospitals outside Daegu. This finding was consistent with our prediction that the ICU census in Daegu would peak on March 16, 2020, at 160 through mitigation efforts, without which it would have reached 300 by late March 2020. CONCLUSION: Older age and male sex were risk factors for ICU admission. In addition, the geographic location of the hospital seems to contribute to the severity of the COVID-19 patients admitted to the ICU and to the ICU capacity.

The Feasibility of a Modified Exclusive Endoscopic Transcanal Transpromontorial Approach for Vestibular Schwannomas.

Objective We evaluated the feasibility of an exclusive endoscopic transcanal transpromontorial approach (EETTA) for the treatment of small vestibular schwannomas (VSs) limited to the internal auditory canal (IAC), and introduced a modification without external auditory canal closure. Methods Between June 2016 and June 2017, seven patients with VS underwent surgery using a modified EETTA. Treatment outcomes, including efficacy of tumor resection, preservation of function, operation time, and quality of life (QOL), were evaluated. Results The patients preoperatively exhibited Koos Grade I/II tumors and severe-to-profound hearing loss. Gross total resection was accomplished in all cases. There were no major complications, and all patients exhibited normal facial nerve function immediately after surgery. The mean follow-up period was 12.9 months. The operation time (average 196.3 ± 64.9 minutes) and hospitalization period (average 7.4 ± 1.0 days) were favorable. Short Form-36 scores for QOL showed unremarkable results compared with previous reports. Conclusions The modified EETTA was effective in the removal of VSs in the IAC. It can be an alternative surgical option for small VSs.

Rottlerin induces cyclooxygenase-2 upregulation through an ATF4 and reactive oxygen species-independent pathway in HEI-OC1 cells.

Hearing loss can be caused by infection, inflammation, loud noise and ototoxic drugs. The induction of cyclooxygenase-2 (COX­2) expression is an important event during the cellular inflammatory response. The present study investigated the effect of rottlerin on CO-2 mRNA and protein expression in HEI-OC1 cells. Cell viability was determined using an MTT assay. Western blotting was used to examine the expression of COX­2, endoplasmic reticulum stress-associated transcription factors and activation of the MAPK pathway. ROS was measured using the fluorescent probe 2', 7'-dichlorodihydrofluorescein diacetate. Treatment with the natural protein kinase C δ inhibitor, rottlerin, was shown to increase COX­2 expression at the protein and mRNA levels in a dose­dependent manner. Rottlerin was shown to induce increased reactive oxygen species (ROS) generation, however, ROS were not critical for rottlerin­induced upregulation of COX­2 expression in HEI­OC1 cells. In addition, rottlerin was shown to increase the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The pharmacological inhibition of p38MAPK and suppression of activating transcription factor 4 (an ER stress­associated transcription factor) expression by small interfering RNA inhibited rottlerin-induced COX­2 upregulation. Furthermore, COX­2 expression levels were increased further when cells were treated with rottlerin and interleukin­1ß or protein kinase C activator, PMA. In conclusion, the results of the present study demonstrated that rottlerin is a novel inducer of COX­2 expression and identified the mechanisms involved in this process. Rottlerin may be considered a potential activator of repair and remodeling.

Objective Tinnitus Concomitant with Eye Blinking: A Case Report.

Tinnitus is a common auditory phenomenon associated with many otological diseases, and is usually subjective. Objective tinnitus can be generated by para-auditory structures, usually derived from vascular or myogenic sources, or the eustachian tube. We present a rare case of intermittent unilateral tinnitus associated with eye blinking. Otoendoscopic examination showed that the external auditory canals and tympanic membranes were normal; however, rhythmic movements of both tympanic membranes, concomitant with the tinnitus, were evident whenever the patient blinked. The tympanometry and stapedial reflexes measured via impedance audiometry exhibited saw-tooth patterns; movement of the tympanic membrane was associated with eyelid blinking. The patient was managed conservatively, with reassurance and medication, and the condition became well-controlled. Here, we present this educational case and review the literature.

Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss.

Previously, we reported the expression levels of specific microRNA machinery components, DGCR8 and AGO2, and their clinical association in patients with idiopathic sudden hearing loss (SSNHL). In the present study, we investigated the other important components of microRNA machinery and their association with clinical parameters in SSNHL patients. Fifty-seven patients diagnosed with SSNHL and fifty healthy volunteers were included in this study. We evaluated mRNA expression levels of Dicer and Drosha in whole blood of patients with SSNHL and the control group, using RT & real-time PCR analysis. The Dicer mRNA expression level was down-regulated in patients with SSNHL. However, the Drosha mRNA expression level was not significantly altered in patients with SSNHL. Neither the Dicer nor Drosha mRNA expression level was not associated with any clinical parameters, including age, sex, duration of initial treatment from onset (days), initial Pure tone average, Siegel's criteria, WBC, and Erythrocyte sedimentation rate. However, mRNA expression levels of Dicer and Drosha were positively correlated to each other in patients with SSNHL. In this study, we demonstrated for the first time that the Dicer mRNA expression level was down-regulated in patients with SSNHL, suggesting its important role in pathobiology of SSNHL development.

The Expression of AGO2 and DGCR8 in Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVES: The microRNAs have been implicated in the development and function of the inner ear, especially in contribution to hearing. However, the impact of idiopathic sudden sensorineural hearing loss (SSNHL) on expression of miRNA biogenesis-related components has not been established. To investigate the regulations of microRNA (miRNA) biogenesis-related components, argonaute 2 (AGO2) and DiGeorge syndrome critical region gene 8 (DGCR8) mRNA expression in SSNHL and to evaluate the value of clinical parameters on their expression. METHODS: Thirty-seven patients diagnosed with SSNHL and fifty-one healthy volunteers were included in this study. We measured mRNA expression levels of AGO2 and DGCR8 in whole blood cells but erythrocytes of patients with SSNHL and controls, using reverse transcription and real-time polymerase chain reaction analysis. RESULTS: The mRNA expression level of AGO2 is upregulated in SSNHL. The expression level of AGO2 was significantly correlated with that of DGCR8 in both patients with SSNHL and controls. Expression level of AGO2 in SSNHL was correlated with white blood cell counts. CONCLUSION: This study demonstrated for the first time that the AGO2 mRNA expression level was upregulated in SSNHL, suggesting its important role in pathobiology of SSNHL development.

Dexamethasone inhibits interleukin-1ß-induced matrix metalloproteinase-9 expression in cochlear cells.

OBJECTIVES: To investigate the effect of interleukin (IL)-1ß on matrix metalloproteinase (MMP)-9 expression in cochlea and regulation of IL-1ß-mediated MMP-9 expression by dexamethasone and the molecular and signaling mechanisms involved. METHODS: House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1ß with/without dexamethasone. Glucocorticoid receptor antagonist, RU486, was used to see the role of dexamethasone. PD98059 (an extracellular signal-regulated kinases [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinases [MAPK] inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor) were also used to see the role of MAPKs signaling pathway(s) in IL-1ß-induced MMP-9 expression in HEI-OC1 cells. Reverse transcription-polymerase chain reaction and gelatin zymography were used to measure mRNA expression level of MMP-9 and activity of MMP-9, respectively. RESULTS: Treatment with IL-1ß-induced the expression of MMP-9 in a dose- and time-dependent manner. IL-1ß (1 ng/mL)-induced MMP-9 expression was inhibited by dexamethasone. Interestingly, p38 MAPK inhibitor, SB203580, significantly inhibited IL-1ß-induced MMP-9 mRNA and MMP-9 activity. However, inhibition of JNKs and ERKs had no effect on the IL-1ß-induced MMP-9 expression. CONCLUSION: These results suggest that the pro-inflammatory cytokine IL-1ß strongly induces MMP-9 expression via activation of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.

Coding of electric pulse trains presented through cochlear implants in the auditory midbrain of awake rabbit: comparison with anesthetized preparations.

Cochlear implant (CI) listeners show limits at high frequencies in tasks involving temporal processing such as rate pitch and interaural time difference discrimination. Similar limits have been observed in neural responses to electric stimulation in animals with CI; however, the upper limit of temporal coding of electric pulse train stimuli in the inferior colliculus (IC) of anesthetized animals is lower than the perceptual limit. We hypothesize that the upper limit of temporal neural coding has been underestimated in previous studies due to the confound of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for single-unit studies of IC neurons with electric stimulation through CI. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second. We found that IC neurons in awake rabbits showed higher spontaneous activity and greater sustained responses, both excitatory and suppressive, at high pulse rates. Maximum pulse rates that elicited synchronized responses were approximately two times higher in awake rabbits than in earlier studies with anesthetized animals. Here, we demonstrate directly that anesthesia is a major factor underlying these differences by monitoring the responses of single units in one rabbit before and after injection of an ultra-short-acting barbiturate. In general, the physiological rate limits of IC neurons in the awake rabbit are more consistent with the psychophysical limits in human CI subjects compared with limits from anesthetized animals.

Better temporal neural coding with cochlear implants in awake animals.

Both the performance of cochlear implant (CI) listeners and the responses of auditory neurons show limits in temporal processing at high frequencies. However, the upper limit of temporal coding of pulse-train stimuli in the inferior colliculus (IC) of anesthetized animals appears to be lower than that observed in corresponding perceptual tasks. We hypothesize that the neural rate limits have been underestimated due to the effect of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for recording responses of single IC neurons to CI stimulation without the confound of anesthesia and compared these data with earlier recordings from the IC of anesthetized cats. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1,280 pulses per second (pps). We found that the maximum pulse rates that elicited sustained firing and phase-locked responses were 2-3 times higher in the IC of awake rabbits than in anesthetized cats. Moreover, about 25 % of IC neurons in awake rabbit showed sustained responses to periodic pulse trains at much higher pulse rates (>1,000 pps) than observed in anesthetized animals. Similar differences were observed in single units whose responses to pulse trains were monitored while the animal was given an injection of an ultrashort-acting anesthetic. In general, the physiological rate limits of IC neurons in awake rabbit are more consistent with the psychophysical limits in human CI subjects compared to the data from anesthetized animals.

Temporal bone histopathology in neurofibromatosis type 2.

OBJECTIVES/HYPOTHESIS: To describe the histopathologic findings in the temporal bone in patients with neurofibromatosis type 2 (NF2). The literature contains limited data on otopathology of NF2. STUDY DESIGN: Basic science study. METHODS: Twenty-six temporal bones from 16 patients with NF2 were examined by light microscopy. The diagnosis of NF2 was made on the basis of bilateral cochleovestibular schwannomas. Clinical information was obtained from review of the medical records. RESULTS: The tumors were multicentric in origin in 19 of 26 (73%) ears. Typically, tumors were seen arising within the internal auditory canal and from various locations within the labyrinth. The majority of schwannomas showed high cellularity with involvement of the labyrinth. Most cases showed significant degrees of degeneration of sensory and neural elements within the cochlea. Fusion tumors were sometimes seen as a result of a schwannoma merging with an adjacent meningioma. Fifteen of 26 (58%) ears showed facial nerve involvement by schwannoma. CONCLUSIONS: Cochleovestibular schwannomas in NF2 are aggressive neoplasms; they are often multicentric and demonstrate a propensity to involve the labyrinth. There is often associated secondary degeneration within the cochlea. These features make total removal of these tumors and their removal with preservation of hearing more difficult than with sporadic unilateral cochleovestibular schwannoma.

A polymorphism at -1607 2G in the matrix metalloproteinase-1 (MMP-1) increased risk of sudden deafness in Korean population but not at -519A/G in MMP-1.

OBJECTIVES/HYPOTHESIS: Matrix metalloproteinase-1 (MMP-1) is associated with a risk of inflammatory disease and cancer invasion. Two common etiologies for sudden deafness (SD) are circulatory disturbance and inflammation. The present study aimed to investigate whether MMP-1 polymorphisms are associated with SD. STUDY DESIGN: Case-control study. Ninety-nine Korean SD patients and 530 normal patients (controls) were used in this study. METHODS: Single nucleotide polymorphism (SNP) of MMP-1 (at -1607G/2G and -519A/G) was analyzed using the pyrosequencing method. RESULTS: At MMP-1 -1607G/2G, the distributions of 2G/2G, G/2G, and G/G genotypes in controls were 36.8%, 44.3%, and 18.9%, respectively, and in SD patients were 46.5%, 48.5%, and 5.1%, respectively. The 2G/2G genotype was found to increase the risk of SD compared with the G/G genotype (codominant model: P = .0029; recessive model: P = .0003). The 2G allele was found to increase the risk of SD compared with the G allele (P = .002). At MMP1 -519A/G, there was no statistically significant increase in the risk of SD. Among haplotypes of MMP-1 polymorphisms -1607G/2G and -519A/G, 2GA and GA were found to be associated with SD (P < .05). CONCLUSIONS: These results suggest that the 2G/2G genotype is associated with an increased risk of SD compared with the G/2G and G/G genotypes. Furthermore, the 2G allele may be a risk factor for SD.

Rottlerin induces heme oxygenase-1 (HO-1) up-regulation through reactive oxygen species (ROS) dependent and PKC delta-independent pathway in human colon cancer HT29 cells.

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by its substrate heme and diverse stimuli. The induction of HO-1 gene expression is one of the important events in cellular response to pro-oxidative and pro-inflammatory insults. In this study, the effect of rottlerin, a putative PKC delta inhibitor, on HO-1 expression in HT29 human colon cancer cells was investigated. Rottlerin-induced HO-1 at both protein and mRNA levels in a dose- and time-dependent manner. Rottlerin-mediated HO-1 induction was abrogated in the presence of N-acetylcysteine (NAC) or glutathione (GSH). Rottlerin induced nuclear translocation of NF-E2-related factor 2 (Nrf2) and increased antioxidant response element (ARE)-driven transcriptional activity. Additionally, rottlerin activated p38 mitogen-activated protein kinase (MAPK) and ERK. The pharmacological inhibition of ERK and p38 MAPK inhibited rottlerin-induced HO-1 up-regulation. However, suppression of protein kinase C delta (PKC delta) expression by siRNA or overexpression of WT-PKC delta did not abrogate the rottlerin-mediated induction of HO-1. These results suggest that rottlerin induces up-regulation of HO-1 via PKC delta-independent pathway. Taken together, the present study identified rottlerin as a novel inducer of HO-1 expression and identified the mechanisms involved in this process.

Staging in vestibular schwannoma surgery: a modified technique.

The authors herein propose the staged excision as a novel strategy to preserve facial nerve and minimize complication during microsurgery of large vestibular schwannoma (VS). At the first stage, for reducing mass effect on the brain stem and cerebellum, subtotal tumor resection was performed via a retrosigmoid craniotomy without intervention of meatal portion of tumor. With total resection of the remaining tumor, the facial nerve was decompressed and delineated during the second stage translabyrinthine approach at a later date. A 38-year-old female who underwent the staging operation for resection of her huge VS is illustrated.

Interleukin-1beta up-regulates inducible nitric oxide by way of phosphoinositide 3-kinase-dependent in a cochlear cell model.

OBJECTIVE: To investigate the effect of interleukin (IL)-1beta on inducible nitric oxide (iNOS) expression in cochlea and the molecular and signaling mechanisms involved. MATERIALS AND METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1beta. Pharmacologic inhibitors such as PD98059 (an extracellular-regulated protein kinase [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinase [MAPK] inhibitor), SP600125 (a c-Jun N-terminal kinases [JNKs]) inhibitor), and LY294002 (an inhibitor of phosphoinositide 3-kinase [PI3 K]) were used to see the role of JNKs, ERKs, p38 MAPK, or PI3 K signaling pathway(s) in iNOS expression in response to IL-1beta in HEI-OC1 cells. Western blot and reverse-transcription polymerase chain reaction analyses were used to measure iNOS protein and mRNA expression, respectively. Luciferase assay was carried out to measure the transcription of iNOS by IL-1beta in HEI-OC1 cells. RESULTS: Treatment of IL-1beta resulted in a concentration-dependent increase of iNOS protein and mRNA and NO production. One nanogram per milliliter of IL-1beta treatment for 4 to 8 hours was sufficient to highly induce iNOS. IL-1beta treatment also led to activation of JNKs, ERKs, and p70S6 K. Interestingly, pharmacologic inhibition of the PI3 K signaling pathway by LY294002 resulted in strong down-regulation of the IL-1beta-induced expressions of iNOS protein and mRNA. However, inhibition of JNKs and ERKs by SP29004 and PD98059, respectively, had no effect on the IL-1beta-induced iNOS expression. CONCLUSIONS: These results suggest that the pro-inflammatory cytokine IL-1beta strongly induces iNOS expression and NO production in HEI-OC1 cells, and the induction appears to be achieved by increased iNOS transcription and activation of PI3 K signaling pathway.

IL4 receptor polymorphism is associated with increased risk of sudden deafness in Korean population.

The interleukin 4 receptor (IL4R) polymorphism Q576R (rs 180275) has been well known to be associated with atopy and other inflammatory diseases. A single nucleotide polymorphism (SNP) A > G transition potentiates the binding specificity of the adjacent tyrosine residue. In this study we investigated the possible relationship between sudden deafness (SD) and IL4R polymorphism Q576R in 97 Korean SD patients and 613 controls using pyrosequencing method. The odds ratio (OR) for SD associated with the G vs. A allele was 2.58 [P < 0.0001, 95% confidence interval (CI) = 1.84-3.60]. We then sub-grouped SD into Tinnitus positive (+) and Tinnitus negative (-). G allele in Tinnitus (+) is significantly associated with the development of Tinnitus (+) [X(2) = 32.02, P < 0.0001, OR (95% CI) = 2.74 (1.91-3.93)] but not with Tinnitus (-). Taken together these results suggest that G allele could be a risk factor for SD.

Structural requirements for the neuroprotective effects of aspirin analogues against N-methyl-D-aspartate and zinc ion neurotoxicity.

In order to elucidate the structural requirements for the dual neuroprotective activity of aspirin against N-methyl-D-aspartate (NMDA) and zinc ion neurotoxicity, various aspirin analogues and derivatives, modified at the carboxylic group, the acetyl group, and the chain length between the carboxylic acid moiety and phenyl ring, were synthesized. Replacement of the carboxylic acid group with alkyl groups (compounds 2c and 2d) resulted in a dramatic increase in neuroprotective activity against NMDA neurotoxicity, while reduction of the carboxylic acid group to the alcohol (compound 2g) completely abolished this activity. In contrast to NMDA neurotoxicity, compounds that are devoid of the carboxylic acid group did not show any activity against zinc ion neurotoxicity. Replacement of the acetyl group with a propionyl (compound 5a) or butyryl group (compound 5b) did not significantly change the activity against NMDA neurotoxicity, but replacement of the acetyl group with a propionyl group (compound 5a) resulted in a slight decrease in activity against zinc ion neurotoxicity. Compound 12, which has ethylene units between the carboxylic acid moiety and phenyl ring in the structure of aspirin, exhibited greater neuroprotective activity against NMDA neurotoxicity than the compared compounds (aspirin, compound 9 and compound 17), which have different chain lengths. A similar trend was also observed in the neuroprotective activity against zinc ion neurotoxicity. These results indicate that the carboxylic acid group in aspirin is not indispensable for the inhibitory effect against NMDA neurotoxicity, but is essential for the inhibitory effect against zinc ion neurotoxicity. The acetyl group and ethylene unit's distance are favourable for the inhibitory effect against NMDA neurotoxicity as well as zinc ion neurotoxicity.