Sher-Wei Lim

Microglial activation induced by traumatic brain injury is suppressed by postinjury treatment with hyperbaric oxygen therapy.

BACKGROUND The mechanisms underlying the protective effects of hyperbaric oxygen (HBO) therapy on traumatic brain injury (TBI) are unclear. TBI initiates a neuroinflammatory cascade characterized by activation of microglia and increased production of proinflammatory cytokines. In this study, we attempted to ascertain whether the occurrence of neuroinflammation exhibited during TBI can be reduced by HBO. METHODS TBI was produced by the fluid percussion technique in rats. HBO (100% O2 at 2.0 absolute atmospheres) was then used at 1 h (HBO I) or 8 h (HBO II) after TBI. Neurobehavior was evaluated by the inclined plane test on the 72 h after TBI and then the rats were killed. The infarction area was evaluated by Triphenyltetrazolium chloride. Immunofluorescence staining was used to evaluate neuronal apoptosis (TUNEL + NeuN), microglial cell aggregation count (OX42 + DAPI), and tumor necrosis factor-alpha (TNF-α) expression in microglia cell (OX42 + TNF-α). RESULTS The maximum grasp angle in the inclined plane test and cerebral infarction of the rats after TBI were significantly attenuated by HBO therapy regardless of whether the rats were treated with HBO 1 or 8 h after TBI compared with the controls. TBI-induced microglial activation, TNF-α expression, and neuronal apoptosis were also significantly reduced by HBO therapy. CONCLUSIONS Our results demonstrate that treatment of TBI during the acute phase of injury can attenuate microgliosis and proinflammatory cytokine TNF-α expression resulting in a neuroprotective effect. Even treating TBI with HBO after 8 h had a therapeutic effect.

Hyperbaric oxygen effects on neuronal apoptosis associations in a traumatic brain injury rat model

BACKGROUND The neuroprotective mechanisms of hyperbaric oxygen (HBO) therapy on traumatic brain injury (TBI) remain unclear, especially neuronal apoptosis associations such as the expression of tumor necrosis factor alpha (TNF-α), transforming growth-interacting factor (TGIF), and TGF-β1 after TBI. The aim of this study was to investigate the neuroprotective effects of HBO therapy in a rat model of TBI. MATERIALS AND METHODS The experimental rats were randomly divided into three groups as follows: TBI + normobaric air (21% O₂ at one absolute atmosphere), TBI + HBO, and sham-operated normobaric air. The TBI + HBO rats received 100% O₂ at 2.0 absolute atmosphere for 1 h immediately after TBI. Local and systemic TNF-α expression, neuropathology, levels of the neuronal apoptosis-associated proteins TGIF and TGF-β1, and functional outcome were evaluated 72 h after the onset of TBI. RESULTS Compared to the TBI control groups, the running speed of rats on the TreadScan after TBI was significantly attenuated by HBO therapy. The TBI-induced local and systemic TNF-α expression, neuronal damage score, and neuronal apoptosis were also significantly reduced by HBO therapy. Moreover, HBO treatment attenuated the expression of TGIF but increased TGF-β1 expression in neurons. CONCLUSIONS We concluded that treatment of TBI with HBO during the acute phase of injury can decrease local and systemic proinflammatory cytokine TNF-α production, resulting in neuroprotective effects. We also suggest that decreased levels of TGIF and increased levels of TGF-β in the injured cortex leading to decreased neuronal apoptosis is one mechanism by which functional recovery may occur.

Chronic Indwelling Urinary Catheter Increase the Risk of Bladder Cancer, Even in Patients Without Spinal Cord Injury.

AbstractChronic indwelling urinary catheters (CIDCs) are known as a risk factor for bladder cancer in patients with spinal cord injury (SCI). This study examined the potential risk of bladder cancer from CIDCs in patients without SCI.The National Health Insurance Research Database in Taiwan was used to identify SCI patients (N = 1816). This group was compared against a control CIDC cohort without SCI (N = 1816) and a reference cohort with normal individuals without SCI and a record of CIDC (N = 7264). Comparisons were made based on age and gender matching over a maximum of 11 follow-up years. The incidence risk and hazard ratio (HR) of bladder cancer were estimated in all 3 groups.During the follow-up period, the bladder cancer incidence rates were 68.90 and 102.53 per 100,000 person-years in the SCI and CIDC-non-SCI groups, respectively. These values were both higher than that of the reference cohort (12.00 per 100,000 person-years). Patients who had history of SCI (HR: 6.51; 95% CI, 2.56–16.52) or CIDC without SCI (HR: 9.11; 95% CI, 3.9–21.29) had a higher risk of bladder cancer compared with the reference cohort.Patients with CIDCs may have an increased risk of bladder cancer development, especially in older aged and male patients compared with general population.

Anxiety and Depression in Patients with Traumatic Spinal Cord Injury: A Nationwide Population-Based Cohort Study

Background Traumatic spinal cord injury (tSCI) may involve new-onset anxiety and depression post-discharge. However, long-term population-based studies have lacked access to follow-up conditions in terms of new-onset anxiety and depression. The objective of this study was to estimate the long-term risk of new-onset anxiety and depression post-discharge. Methods The Longitudinal Health Insurance Database 2000 (LHID2000) from Taiwan’s National Health Insurance Research Database was used in this study. Individuals with tSCI were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes of 806 and 952 from 1999–2008. The comparison cohort (other health conditions group) was randomly selected from the LHID2000 and was 1:1 matched by age, sex, index year, and comorbidities to reduce the selection bias. All study participants were retrospectively followed for a maximum of 3 years until the end of follow-up, death, or new-onset anxiety (ICD-9-CM: 309.2–309.4) or depression (ICD-9-CM: 296.2, 296.5, 296.82, 300.4, 309.0–309.1, and 311). Persons who were issued a catastrophic illness card for tSCI were categorized as having a severe level of SCI (Injury Severity Score [ISS] ≥16). Poisson regression was used to estimate the incidence rate ratios of anxiety or depression between patients with tSCI and other health conditions. The relative risk of anxiety or depression was estimated using a Cox regression analysis, which was adjusted for potential confounding factors. Results Univariate analyses showed that the tSCI patients (n = 3556) had a 1.33 times greater incidence of new-onset anxiety or depression (95% confidence interval [CI]: 1.12–1.57) compared to the other health conditions group (n = 3556). After adjusting for potential risk factors, the tSCI patients had a significant 1.29-fold increased risk of anxiety or depression compared to the group with other health conditions (95% CI: 1.09–1.53). Individuals with tSCI, including patients who were under the age of 35, patients who were males, patients who had a low income, and patients without a Charlson Comorbidity Index score, all had a higher long-term risk of anxiety or depression than the other health conditions group (IRRs: 1.84, 1.63, 1.29, and 1.39, respectively). For all tSCI patients, those with an Injury Severity Score (ISS) ≥16 had an almost 2-fold higher risk of anxiety or depression (adjusted Hazard Ratio: 1.85; 95% CI: 1.17–2.92) compared to those with ISS <16. Conclusions Our findings indicated that tSCI patients have a high risk of anxiety or depression post-discharge, especially among the younger tSCI patients (age <50 years), compared with the other health conditions group. This information could help physicians understand the long-term risk of new-onset anxiety or depression in tSCI patients post-discharge.

Hyperbaric Oxygen Effects on Depression-Like Behavior and Neuroinflammation in Traumatic Brain Injury Rats

OBJECTIVE The aim of this study was to determine whether hyperbaric oxygen (HBO) therapy causes attenuation of traumatic brain injury (TBI)-induced depression-like behavior and its associated anti-neuroinflammatory effects after fluid percussion injury. METHODS Anesthetized male Sprague-Dawley rats were divided into 3 groups: sham operation plus normobaric air (NBA) (21% oxygen at 1 absolute atmosphere [ATA]), TBI plus NBA, and TBI plus HBO (100% oxygen at 2.0 ATA). HBO was applied immediately for 60 min/d after TBI for 3 days. Depression-like behavior was tested by a forced swimming test, motor function was tested by an inclined plane test, and infarction volume was tested by triphenyltetrazolium chloride (TTC) staining on days 4, 8, and 15. Neuronal apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling assay), microglial (marker OX42) activation, and tumor necrosis factor (TNF)-α expression in microglia in the hippocampus CA3 were measured by immunofluorescence methods. RESULTS Compared with the TBI controls, without significant changes in TTC staining or in the motor function test, TBI-induced depression-like behavior was significantly attenuated by HBO therapy by day 15 after TBI. Simultaneously, TBI-induced neuronal apoptosis, microglial (marker OX42) activation, and TNF-α expression in the microglia in the hippocampus CA3 were significantly reduced by HBO. CONCLUSIONS Our results suggest that HBO treatment may ameliorate TBI-induced depression-like behavior in rats by attenuating neuroinflammation, representing one possible mechanism by which depression-like behavior recovery might occur. We also recommend HBO as a potential treatment for TBI-induced depression-like behavior if early intervention is possible.