The executive functions among patients with an initial Glasgow coma scale score of 15.

Executive functions (EF) were the critical neuropsychological functions linked to long-term adaptation. Given the heterogeneous prognosis trajectories of mild traumatic brain jury (mTBI), the mildest TBI may not always be benign in the chronic stage. The present study explored the long-term EF in patients with chronic complicated mTBI and a Glasgow Coma Scale (GCS) score of 15. Fifty patients with complicated mTBI and GCS scores of 15 and 35 control participants were recruited in this study. Medical records were retrospectively analyzed, and neuropsychological assessments and subjective measures examined the neuropsychological functions. Compared with healthy controls, complicated mTBI patients with a GCS score of 15 performed significantly worse on most EF assessments, including longer reaction time (RT) and poor cognitive flexibility and abstract reasoning performances. Patients also reported more EF problems and lower quality of life (QoL) than healthy controls. Females and those with subdural hematoma (SDH) had significantly longer reaction times (RT) on executive attention tests. This study found that complicated mTBI with a GCS score of 15 had incomplete recovery of EF, even in the chronic stage. We suggest that early neuropsychological assessment and rehabilitation should be arranged for such patients.

Pretreatment with Lovastatin Improves Depression-Like Behavior After Traumatic Brain Injury Through Activation of the AMPK Pathway.

BACKGROUND: The beneficial effect of pretreatment with statins on traumatic brain injury (TBI)-induced depression and anxiety and its mechanism of action remain unclear. In this study, we combined epidemiological and experimental animal data to clarify this issue. METHODS: We used the Taiwan National Health Insurance database to identify patients who were diagnosed with TBI from 2000 to 2013 and compared patients with and without statin treatment matched by age, sex, and underlying comorbidities in a 1:1 ratio. The risk of developing depression and/or anxiety was compared between patients with and without a statin using Cox proportional hazards regression. We also used a rat model to assess the effect of lovastatin pretreatment on neurobehavioral and neuropathological changes following TBI. RESULTS: The risk of developing depression was lower in the 41,803 patients in the statin cohort than nonstatin cohort (adjusted hazard ratio, 0.91 [95% confidence interval, 0.83-0.99]). In animal models, the lovastatin group had significantly reduced infarct volume, decreased immobility time and latency to eat, a reduced number of Fluoro- Jade-positive cells and levels of glial fibrillary acidic protein and tumor necrosis factor-alpha, and increased adenosine monophosphate -activated protein kinase (AMPK) and its upstream kinase liver kinase B1 in the hippocampal dentate gyrus. These effects were blocked in AMPK inhibitor-pretreated TBI rats. CONCLUSIONS: Our epidemiological data showed that a decreased risk of depression was associated with statin pretreatment, which was supported by an animal study. The underlying mechanism for this appears to involve AMPK activation in the statin pretreatment-induced alleviation of TBI.

Efficacy of acupuncture for pain relief in patients receiving extracorporeal shock wave lithotripsy: a meta-analysis of randomized controlled studies.

Background: This meta-analysis aimed at investigating the efficacy of acupuncture for pain relief in patients receiving extracorporeal shock wave lithotripsy (ESWL). Methods: Randomized controlled trials comparing the efficacy of acupuncture with conventional treatments were retrieved from major electronic databases (e.g., MEDLINE, EMBASE, and Cochrane Library) until August 28, 2022. The primary outcome was the response rate (i.e., rate of pain relief), while secondary outcomes included stone-free rate, satisfaction rate, duration of ESWL, peri-/post-procedural pain score, and risk of adverse events. Results: Thirteen eligible studies involving 1,220 participants published between 1993 and 2022 were analyzed. Pooled results indicated that acupuncture had a better response rate compared to conventional treatments (RR = 1.17, 95% CI: 1.06-1.3, p = 0.003, seven trials, n = 832). Despite no difference in ESWL duration (MD = 0.02 min, 95% CI: -1.53 to 1.57, p = 0.98, three trials, n = 141), stone-free rate (RR = 1.11, 95% CI: 1-1.25, p = 0.06, six trials, n = 498), and satisfaction rate (RR = 1.51, 95% CI: 0.92-2.47, p = 0.1, three trials, n = 334) between the two groups, the acupuncture group had a lower risk of adverse events (RR = 0.51, 95% CI: 0.33-0.79, p = 0.003, five trials, n = 327), peri- (MD = -1.91 points, 94% CI: -3.53 to -0.28, p = 0.02, four trials, n = 258 patient) and post-procedural (MD = -1.07, 95% CI: -1.77 to -0.36, p = 0.003, four trials, n = 335) pain score. Conclusion: The results of this meta-analysis showed that the use of acupuncture in patients receiving ESWL was associated with a higher pain relief rate and a lower risk of adverse events, suggesting feasibility of its use in this clinical setting. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022356327.

Neuropsychological Impairments in Patients With Post-traumatic Epilepsy: A Scoping Review.

OBJECTIVES: To date, the research on the prognosis of the neuropsychological function of patients with post-traumatic seizure (PTE) is sparse. This study aimed to systematically map the literature's extent, range, and characteristics regarding PTE and neuropsychological impairments. METHODS: A systematic literature search was conducted in CINAHL, Cochrane, Embase, Medline, PubMed, Scopus, Web of Science, and ScienceDirect databases. The search terms were related to PTE and neuropsychological impairments. RESULTS: This scoping review included seven studies, two of which examined the impact of PTE on neuropsychological outcomes. Among the three studies that used neuropsychological assessments, attention/concentration, and memory were the most frequently assessed domains. Only one study reported a significant difference between PTE and non-PTE patients. The cognitive rating scale findings in the other four studies were similar, indicating that patients with PTE performed worse than those without PTE. CONCLUSIONS: The results of this review suggest that patients with PTE may have neuropsychological function impairments. More attention needs to be paid to older patients and those with higher brain injury and seizure severity. Additional investigation is necessary to determine the clinical characteristics of TBI and PTE and elucidate the relations between PTE and specific neuropsychological domains.

Patient-Specific 3D-Print Extracranial Vascular Simulators and Infrared Imaging Platform for Diagnostic Cerebral Angiography Training.

Tortuous aortic arch is always challenging for beginner neuro-interventionalists. Herein, we share our experience of using 3D-printed extracranial vascular simulators (VSs) and the infrared imaging platform (IRIP) in two training courses for diagnostic cerebral angiography in the past 4 years. A total of four full-scale patient-specific carotid-aortic-iliac models were fabricated, including one type I arch, one bovine variant, and two type III arches. With an angiography machine (AM) as the imaging platform for the practice and final test, the first course was held in March 2018 had 10 participants, including three first-year residents (R1), three second-year residents (R2), and four third-year residents (R3). With introduction of the IRIP as the imaging platform for practice, the second course in March 2022 had nine participants, including 3 R1s, 3 R2s, and 3 R3s. The total manipulation time (TMT) to complete type III aortic arch navigation was recorded. In the first course, the average TMT of the first trial was 13.1 min. Among 3 R1s and 3 R2s attending the second trial, the average TMT of the second trial was 3.4 min less than that of the first trial. In the second course using IRIP, the average TMT of the first and second trials was 6.7 min and 4.8 min, respectively. The TMT of the second trial (range 2.2~14.4 min; median 5.9 min) was significantly shorter than that of the first trial (range 3.6~18 min; median 8.7 min), regardless of whether AM or IRIP was used (p = 0.001). Compared with first trial, the TMT of the second trial was reduced by an average of 3.7 min for 6 R1s, which was significantly greater than the 1.7 min of R2 and R3 (p = 0.049). Patient-specific VSs with radiation-free IRIP could be a useful training platform for junior residents with little experience in neuroangiography.

A novel surgical technique in transforaminal lumbar interbody fusion by the bone graft delivery device: evaluation of therapeutic effect in patients with minimally invasive spine surgery.

BACKGROUND: Transforaminal Lumbar Interbody Fusion (TLIF) is commonly associated with higher complications and longer operative time. This study aims to evaluate the effectiveness, safety, and usability of a novel minimally invasive surgery (MIS) bone graft delivery device. METHODS: 73 consecutive patients with lumbar spondylosis, degenerative disc disease, spondylolisthesis, scoliosis or trauma were enrolled in this randomized controlled trial. Group 1 comprised 39 patients treated with the novel MIS bone graft delivery device. Group 2 consisted of 34 patients treated with the conventional system. The primary objective of the study was the assessment of the amount of bone graft delivery using the device. The secondary objectives were the effect of the device on operative time, pain relief, disability improvement, and bone fusion grade. RESULTS: Bone delivery amount was significantly higher in the MIS device group (6.7 ± 2.9 mL) compared to the conventional group (2.3 ± 0.5 mL), p < 0.001. Regarding the operation time, the MIS device group was associated significantly lower duration than the conventional group (p < 0.001). After a 3-month follow-up, 39.5% of the patients in the MIS device group and 3.5% of the patients in the conventional group were observed to achieve grade I fusion (complete fusion). There was a significant difference in fusion success rates (p < 0.01). CONCLUSION: The novel MIS bone graft delivery device was associated with successful bone delivery. Our MIS device provides promising modality with less operative time and higher bone fusion rates than conventional modalities. Trial Registration This trial was retrospectively registered on ClinicalTrials.gov (Registration date: 11/19/2021; Registration number: NCT05190055).

Elevated Surgical Pleth Index at the End of Surgery Is Associated with Postoperative Moderate-to-Severe Pain: A Systematic Review and Meta-Analysis.

Despite acceptance of the surgical pleth index (SPI) for monitoring the intraoperative balance between noxious stimulation and anti-nociception under general anesthesia, its efficacy for predicting postoperative moderate-to-severe pain remains unclear. We searched electronic databases (e.g., Google Scholar, MEDLINE, Cochrane Library, and EMBASE) to identify articles focusing on associations of SPI at the end of surgery with immediate moderate-to-severe pain in the postanesthesia care unit from inception to 7 July 2022. A total of six observational studies involving 756 adults published between 2016 and 2020 were eligible for quantitative syntheses. Pooled results revealed higher values of SPI in patients with moderate-to-severe pain than those without (mean difference: 7.82, 95% CI: 3.69 to 11.95, p = 0.002, I2 = 46%). In addition, an elevated SPI at the end of surgery was able to predict moderate-to-severe pain with a sensitivity of 0.71 (95% confidence interval (CI): 0.65-0.77; I2 = 29.01%) and a specificity of 0.58 (95% CI: 0.39-0.74; I2 = 79.31%). The overall accuracy based on the summary receiver operating characteristic (sROC) curve was 0.72. In conclusion, this meta-analysis highlighted the feasibility of the surgical pleth index to predict postoperative moderate-to-severe pain immediately after surgery. Our results from a limited number of studies warrant further investigations for verification.

A Computer-Assisted System for Early Mortality Risk Prediction in Patients with Traumatic Brain Injury Using Artificial Intelligence Algorithms in Emergency Room Triage.

Traumatic brain injury (TBI) remains a critical public health challenge. Although studies have found several prognostic factors for TBI, a useful early predictive tool for mortality has yet to be developed in the triage of the emergency room. This study aimed to use machine learning algorithms of artificial intelligence (AI) to develop predictive models for TBI patients in the emergency room triage. We retrospectively enrolled 18,249 adult TBI patients in the electronic medical records of three hospitals of Chi Mei Medical Group from January 2010 to December 2019, and undertook the 12 potentially predictive feature variables for predicting mortality during hospitalization. Six machine learning algorithms including logistical regression (LR) random forest (RF), support vector machines (SVM), LightGBM, XGBoost, and multilayer perceptron (MLP) were used to build the predictive model. The results showed that all six predictive models had high AUC from 0.851 to 0.925. Among these models, the LR-based model was the best model for mortality risk prediction with the highest AUC of 0.925; thus, we integrated the best model into the existed hospital information system for assisting clinical decision-making. These results revealed that the LR-based model was the best model to predict the mortality risk in patients with TBI in the emergency room. Since the developed prediction system can easily obtain the 12 feature variables during the initial triage, it can provide quick and early mortality prediction to clinicians for guiding deciding further treatment as well as helping explain the patient's condition to family members.

New diagnosis of cancer in mild and moderate/severe traumatic brain injury patients in a 12-year population-based study.

BACKGROUND: Traumatic brain injury (TBI) has been reported as a risk factor for brain cancer development. However, the magnitude of the impact of TBI on systemic cancer development has not been clarified. METHODS: A retrospective longitudinal cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2011. A total of 35,306 patients were initially enrolled, and 14,795 patients with mild TBI and 14,795 patients with moderate/severe TBI were matched using the National Health Insurance Research Database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of TBI adjusted for potential confounding factors. RESULTS: After matching, the results showed that patients with moderate/severe TBI had a high mortality rate (17.7% vs. 10.4%) and shorter time interval from TBI to death (mean 3.6 years vs. 5.8 years). No differences were observed in cancer incidence (4.1% vs. 4.1%) or risk factors for mortality between mild and moderate/severe TBI patients. However, patients aged between 46 and 55 years, female patients, and patients with pre-existing renal disease had a significant higher cancer incidence risk in moderate/severe TBI compared with mild TBI patients. The top 15 most common cancers showed that mild TBI patients had a higher percentage of head and neck cancer. The overall mortality rate in all TBI patients diagnosed with cancer was about 50%, and the cancer-specific mortality is approximately 85% in death of TBI patients with cancer. CONCLUSIONS: We concluded that the incidence risk of a new cancer diagnosis and mortality risk of TBI patients with cancer between the mild TBI and moderate/severe TBI patients were not significantly different.

Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca2+ Channel Suppression: A Possible Neuroprotective Mechanism.

The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). CGA inhibited 4-aminopyridine (4-AP)-induced glutamate release from synaptosomes. This inhibition was prevented in the absence of extracellular Ca2+ and was associated with the inhibition of 4-AP-induced elevation of Ca2+ but was not attributed to changes in synaptosomal membrane potential. In line with evidence observed through molecular docking, CGA did not inhibit glutamate release in the presence of P/Q-type Ca2+ channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca2+ channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca2+/calmodilin-dependent kinase II (CaMKII) inhibitors, and CGA reduced the phosphorylation of CaMKII and its substrate, synapsin I. Furthermore, pretreatment with intraperitoneal CGA injection attenuated the glutamate increment and neuronal damage in the rat cortex that were induced by kainic acid administration. These results indicate that CGA inhibits glutamate release from cortical synaptosomes by suppressing P/Q-type Ca2+ channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons.

Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects.

BACKGROUND: Ceftriaxone is a ß-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. METHODS: Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn's Gram staining. These parameters above were measured at 72 h after TBI. RESULTS: Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. CONCLUSIONS: The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Rosmarinic Acid, a Bioactive Phenolic Compound, Inhibits Glutamate Release from Rat Cerebrocortical Synaptosomes through GABAA Receptor Activation.

Rosmarinic acid, a major component of rosemary, is a polyphenolic compound with potential neuroprotective effects. Asreducing the synaptic release of glutamate is crucial to achieving neuroprotectant's pharmacotherapeutic effects, the effect of rosmarinic acid on glutamate release was investigated in rat cerebrocortical nerve terminals (synaptosomes). Rosmarinic acid depressed the 4-aminopyridine (4-AP)-induced glutamate release in a concentration-dependent manner. The removal of extracellular calcium and the blockade of vesicular transporters prevented the inhibition of glutamate release by rosmarinic acid. Rosmarinic acid reduced 4-AP-induced intrasynaptosomal Ca2+ elevation. The inhibition of N-, P/Q-type Ca2+ channels and the calcium/calmodulin-dependent kinase II (CaMKII) prevented rosmarinic acid from having effects on glutamate release. Rosmarinic acid also reduced the 4-AP-induced activation of CaMKII and the subsequent phosphorylation of synapsin I, the main presynaptic target of CaMKII. In addition, immunocytochemistry confirmed the presence of GABAA receptors. GABAA receptor agonist and antagonist blocked the inhibitory effect of rosmarinic acid on 4-AP-evoked glutamate release. Docking data also revealed that rosmarinic acid formed a hydrogen bond with the amino acid residues of GABAA receptor. These results suggested that rosmarinic acid activates GABAA receptors in cerebrocortical synaptosomes to decrease Ca2+ influx and CaMKII/synapsin I pathway to inhibit the evoked glutamate release.

The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury.

BACKGROUND: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). METHODS: Anesthetized male Sprague-Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-D-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. RESULTS: The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. CONCLUSIONS: We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

A novel wireless optical technique for quantitative evaluation of cerebral perfusion pressure in a fluid percussion animal model of traumatic brain injury.

BACKGROUND: Cerebral perfusion pressure (CPP) calculated by mean arterial pressure (MAP) minus intracranial pressure (ICP) is related to blood flow into the brain and reflects cerebral ischemia and oxygenation indirectly. Near-infrared spectroscopy (NIRS) can assess cerebral ischemia and hypoxia non-invasively and has been widely used in neuroscience. However, the correlation between CPP and NIRS, and its potential application in traumatic brain injury, has seldom been investigated. METHODS: We used a novel wireless NIRS system and commercial ICP and MAP devices to assess the trauma to rat brains using different impact intensity. The relationship between CPP and NIRS parameters with increasing impact strength were investigated. RESULTS: The results showed that changes in CPP (∆CPP), oxy-hemoglobin {∆[HbO2]}, total-hemoglobin {∆[HbT]}, and deoxy-hemoglobin were inversely proportional to the increase in impact intensity, and the correlations between ∆CPP, NIRS parameters {∆[HbO2], and ∆[HbT]} were significant. CONCLUSIONS: The NIRS system can assess cerebral ischemia and oxygenation non-invasively and changes of HbO2 and HbT may be used as reference parameters to assess the level of CPP in an animal model of traumatic brain injury.

Fingolimod inhibits glutamate release through activation of S1P1 receptors and the G protein ßγ subunit-dependent pathway in rat cerebrocortical nerve terminals.

Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator approved for treating multiple sclerosis, is reported to prevent excitotoxic insult. Because excessive glutamate release is a major cause of neuronal damage in various neurological disorders, the effect of fingolimod on glutamate release in rat cerebrocortical nerve terminals (synaptosomes) was investigated in the current study. Fingolimod decreased 4-aminopyridine (4-AP)-stimulated glutamate release and calcium concentration elevation. Fingolimod-mediated inhibition of 4-AP-induced glutamate release was dependent on extracellular calcium, persisted in the presence of the glutamate transporter inhibitor DL-TBOA or intracellular Ca2+-releasing inhibitors dantrolene and CGP37157, and was prevented by blocking vesicular transporters or N- and P/Q-type channels. Western blot and immunocytochemical analysis revealed the presence of S1P1 receptor proteins in presynaptic terminals. Fingolimod-mediated inhibition of 4-AP-induced glutamate release was also abolished by the sphingosine kinase inhibitor DMS, selective S1P1 receptor antagonist W146, Gi/o protein inhibitor pertussis toxin, and G protein ßγ subunit inhibitor gallein; however, it was unaffected by the adenylyl cyclase inhibitor SQ22536, protein kinase A inhibitor H89, and phospholipase C inhibitor U73122. These data indicate that fingolimod decreases glutamate release from rat cerebrocortical synaptosomes by suppressing N- and P/Q-type Ca2+ channel activity; additionally, the activation of presynaptic S1P1 receptors and the G protein ßγ subunit participates in achieving the effect.

Triglyceride is a Good Biomarker of Increased Injury Severity on a High Fat Diet Rat After Traumatic Brain Injury.

Injury severity is correlated with poor prognosis after traumatic brain injury (TBI). It is not known whether triglycerides (TGs) or total cholesterol (TC) is good biomarker of increased injury of neuroinflammation and apoptosis in a high fat diet (HFD)-treated rat after TBI episodes. Five-week-old male Sprague-Dawley (SD) rats were fed a HFD for 8 weeks. The anesthetized male SD rats were divided into three sub-groups: sham-operated and TBI with 1.6 atm or with 2.4 atm fluid percussion injury (FPI). Cell infarction volume (triphenyltetrazolium chloride stain), tumor necrosis factor-alpha (TNF-α) expression in the microglia (OX42 marker) and astrocytes (Glial fibrillary acidic protein marker), TNF-α receptor expression in the neurons (TNFR1 and TNFR2 markers), and the extent of neuronal apoptosis (TUNEL marker) were evaluated by immunofluorescence, and the functional outcome was assessed by an inclined plane test. These tests were performed 72 h after TBI. Serum triglyceride and cholesterol levels were measured at 24, 48 and 72 h after TBI. The FPI with 2.4 atm significantly increased body weight loss, infarction volume, neuronal apoptosis and TNF-α expression in the microglia and astrocytes, and it decreased the maximum grasp degree and TNFR1 and TNFR2 expression in neurons at the 3rd day following TBI. The serum TG level was positively correlated with FPI force, infarction volume, Neu-N-TUNEL, GFAP-TNFα, and OX42-TNFα Simultaneously; the serum TG level was negatively correlated with Neu-N-TNFR1 and Neu-N-TNFR2. TG is a good biomarker of increased injury for neuroinflammation and apoptosis at the 3rd day after TBI in HFD rats.

Spontaneous Spinal Epidural Hematoma After Normal Spontaneous Delivery with Epidural Analgesia: Case Report and Literature Review.

BACKGROUND: Pregnancy is a known risk factor for spontaneous spinal epidural hematoma. During cesarean section or vaginal delivery, the unstable hemodynamic status that may occur owing to fluctuation of intra-abdominal pressure increases the possibility of spontaneous spinal epidural hematoma. During labor and the postpartum period, neurologic symptoms may be masked by labor pain or anesthesia block, which makes early diagnosis difficult, especially in the obstetric clinic without a neurologist or neurosurgeon. CASE DESCRIPTION: A 28-year-old woman who had a normal spontaneous delivery under epidural anesthesia developed bilateral lower limb flaccid paralysis and loss of sensation 12.5 hours after delivery. Magnetic resonance imaging showed a 5.2 × 0.9 × 2 cm spinal epidural hematoma with severe spinal cord stenosis at the T2-T5 level with no evidence of a vascular anomaly. After emergent evacuation of the spinal epidural hematoma, lower limb muscle power improved from 0/5 to 1/5, and sensation gradually returned to bilateral lower limbs 22 days postoperatively. Deep vein thrombosis developed at 35 days postoperatively, and an inferior vena cava filter was implanted with urokinase infusion for thrombolytic therapy. She was discharged on day 52 after admission, and lower limb muscle power returned to normal after 3 months. CONCLUSIONS: Clinicians should observe postpartum women for signs of myelopathy or back tenderness and closely monitor neurologic function until anesthesia has run its course. A prompt diagnosis can enable prompt intervention.

The Short-Term Effects of Isolated Traumatic Brain Injury on the Heart in Experimental Healthy Rats.

BACKGROUND: To date, cardiac dysfunction after traumatic brain injury (TBI) has not been consistent. In this study, we hypothesized that TBI may play a role in the development of new-onset cardiac dysfunction in healthy experimental rats. MATERIALS AND METHODS: Anesthetized healthy male Sprague-Dawley rats were divided into two groups: a sham-operated control group and a TBI group. The brain was injured with 2.4 atm percussion via a fluid percussion injury model. During the 120 min after TBI, we continuously measured brain parameters, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and cardiac parameters, such as heart rate (HR), inter-ventricular septum dimension (IVSD), left ventricular internal dimension diastole (LVIDd), end-diastolic volume (EDV), ejection fraction (EF), fractional shortening (FS), and LV mass diastole (LVd mass) by cardiac echo. On days 1, 3, 7, and 14 after TBI, the brain damage volume was evaluated with triphenyltetrazolium chloride; the physiological parameters of the heart, including HR, IVSd, LVIDd, EDV, EF, FS, and LVd mass, were evaluated with cardiac echo; the morphology of cardiomyocytes was examined by hematoxylin and eosin (HE) and Masson trichrome staining; and the biomarkers of cardiac injury troponin I and B-type natriuretic peptide (BNP) were also examined. RESULTS: Compared to sham-operated controls, the TBI groups had higher ICP, lower CPP, and higher brain neuronal apoptosis and infarction contusion volume. The impact of TBI on heart function showed hyperdynamic response trends in IVSd, LVIDd, EDV, EF, FS, and LVd mass within 30 min after TBI; however, EF and FS exhibited eventual decreasing trends. Simultaneously, the values of the biomarkers troponin I and BNP were within normal limits, and HE and Mass trichrome staining revealed no significant differences between the sham-operated control group and the TBI group. CONCLUSIONS: Our results suggest that TBI due to 2.4 atm fluid percussion injury in healthy experimental rats may cause significant damage to the brain and affect the heart function as investigated by cardiac echo but not as investigated by HE and Masson trichrome stainings or troponin I and BNP evaluation.

Effects of a High-Fat Diet on Neuroinflammation and Apoptosis in Acute Stage After Moderate Traumatic Brain Injury in Rats.

BACKGROUND: A high-fat diet (HFD) is correlated with a higher risk of metabolic syndrome. The effect of HFD on neuroinflammation and apoptosis in acute stage after traumatic brain injury (TBI) in rats is not well known. MATERIALS AND METHODS: Five-week-old male Sprague-Dawley (SD) rats were fed a HFD or normal diet (ND) for 8 weeks. Anesthetized male SD rats were divided into two subgroups: sham-operated and TBI. Motor function was measured using an inclined plane. The numbers of apoptotic neurons (markers Neu-N, TUNEL, caspase-3), activated astrocytes (marker GFAP) and microglia (marker OX42), and TNF-α expression in microglia and astrocytes in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the 3rd day after TBI. RESULTS: Rats fed a HFD for 8 weeks had higher body weight, serum cholesterol, and triglycerides. TBI-induced motor deficits, neuronal decrease, neuronal apoptosis, astrocyte and microglia activation, and TNF-α expression in microglia and astrocytes in the ischemia cortex were significantly increased in ND and HFD rats compared to sham rats. However, these parameters were not significantly different between the ND and HFD TBI groups, except motor deficit. CONCLUSIONS: HFD has no significant effects on neuronal apoptosis or neuroinflammation in acute stage compared with ND for 8 weeks after moderate TBI in experimental rats.

Xanthohumol, an active constituent from hope, affords protection against kainic acid-induced excitotoxicity in rats.

Excitotoxicity induced by excessive glutamate has been implicated in many brain disorders. Xanthohumol is a natural product derived from hops (Humulus lupulus L.), which is reported to have glutamate release-inhibiting activity. However, it is unknown whether xanthohumol has protective effects against glutamate-induced excitotoxicity. This study investigated the potential action of xanthohumol in a rat model of excitotoxicity induced by intraperitoneal injection of kainic acid (KA). Xanthohumol (10 or 50 mg/kg) administrated intraperitoneally 30 min prior to KA (15 mg/kg) considerably ameliorated KA-induced seizures, glutamate concentration elevation, and CA3 neuron death. The decrease of mitochondrial fusion protein Mfn-2 and antiapoptotic protein Bcl-2 expression in hippocampal tissues following KA injection were reversed by xanthohumol. Moreover, apoptotic protease activating factor 1 (Apaf-1) expression and caspase-3 activation in the hippocampus were inhibited by xanthohumol. These results suggest that xanthohumol up-regulates Mfn-2 and Bcl-2 to preserve mitochondrial function and suppress Apaf-1 and caspase-3 activation, thereby increasing neuron survival in rats after KA treatment. Therefore, xanthohumol has great potential for development into a therapeutic agent for improving glutamate-related nervous system diseases.