James Mills

Docosahexaenoic Acid Reduces Traumatic Axonal Injury in a Rodent Head Injury Model

Traumatic brain injury (TBI) remains the most common cause of death in persons under age 45 in the Western world. Recent evidence from animal studies suggests that supplementation with omega-3 fatty acids (O3FA) improves functional outcomes following focal neural injury. The purpose of this study is to determine the benefits of DHA supplementation following diffuse axonal injury in rats. Four groups of 10 adult male Sprague-Dawley rats were subjected to an impact acceleration injury and then received 30 days of supplementation with either 10 mg/kg/d or 40 mg/kg/d of docosahexaenoic acid (DHA). Serum fatty acid levels were determined from the isolated plasma phospholipids prior to injury and at the end of the 30 days of DHA supplementation. Following sacrifice, brainstem white matter tracts underwent fluorescent immunohistochemical processing for labeling of β-amyloid precursor protein (APP), a marker of axonal injury. Dietary supplementation with either 10 mg/kg/d or 40 mg/kg/d of DHA for 30 days results in significantly (p < 0.05) increased DHA serum levels of 123% and 175% over baseline, respectively. Immunohistochemical analysis reveals significantly (p < 0.05) decreased numbers of APP-positive axons in animals receiving dietary supplementation with DHA, 26.1 (SD 5.3) for 10 mg/kg/d, and 19.6 (SD 4.7) for 40 mg/kg/d axons per mm(2), versus 147.7 (SD 7.1) axons in unsupplemented animals. Sham-injured animals had 6.4 (SD 13.9) APP positive axons per mm(2). Dietary supplementation with DHA increases serum levels in a dose-dependent manner. DHA supplementation significantly reduces the number of APP-positive axons at 30 days post-injury, to levels similar to seen those in uninjured animals. DHA is safe, affordable, and readily available worldwide to potentially reduce the burden of TBI.

Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury.

BACKGROUND: Although various strategies for prevention of brain disease have been implemented, no substance has been found to be advantageous for prophylaxis against brain injury. OBJECTIVE: While previous work in our laboratory and others have shown positive effects using the omega-3 fatty acid docosahexaenoic acid (DHA) in post-injury treatment following traumatic and ischemic insults, we wished to test its effects when given prior to injury. We have attempted to measure anatomical, cellular, and behavioral outcomes with a prophylactic administration of DHA. METHODS: Five groups of 16 adult male Sprague-Dawley rats were subjected to an impact acceleration traumatic brain after having received a prior administration of DHA in doses of 3, 12, and 40 mg/kg for 30 days prior. Serum fatty acid levels were determined from isolated plasma phospholipids at baseline and at the end of 30 days supplementation. Following sacrifice 1 week after injury, brainstem white matter tracts underwent fluorescent immunohistochemical processing for labeling of beta amyloid precursor protein (APP), an anatomical marker of brain injury, as well as measurements of CD68 and caspase-3 levels, and water maze testing was used for behavioral assessment. RESULTS: Dietary supplementation with DHA resulted in increased serum DHA levels proportionate with the escalating dosage. Immunohistochemical analysis revealed significantly (P < .05) decreased numbers of APP levels in all groups of animals receiving pre-injury supplementation with DHA of 4, 12, and 40 mg/kg at 13955, 4186, and 2827 axons per mm3, respectively, vs 37442 in unsupplemented animals, as measured by stereological methodology. Using a selective measuring technique, only the highest dosage group, 40 mg/kg showed significantly (P < .05) decreased numbers of APP positive axons, at 1.15 axons per high power field vs 6.78 in unsupplemented animals. CD-68, caspase-3, and water maze testing all were significantly (P < .05) improved in the high dose group. CONCLUSION: Dietary supplementation with DHA increases serum levels and, if given prior to traumatic brain injury, reduces the injury response, as measured by axonal injury counts, markers for cellular injury and apoptosis, and memory assessment by water maze testing. This uniform response was seen for the highest dosage group, 40 mg/kg given over 30 days prior to injury, but when measured by stereological counting methodology there was a positive response to anatomical injury across low to high doses of DHA. The potential for DHA to provide prophylactic benefit to the brain against traumatic injury appears promising and requires further investigation.

Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model

OBJECT Traumatic brain injury remains the most common cause of death in persons under 45 years of age in the Western world. Recent evidence from animal studies suggests that supplementation with omega-3 fatty acid (O3FA) (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) improves functional outcomes following focal neural injury. The purpose of this study is to determine the benefits of O3FA supplementation following diffuse axonal injury in rats. METHODS Forty adult male Sprague-Dawley rats were used. Three groups of 10 rats were subjected to an impact acceleration injury and the remaining group underwent a sham-injury procedure (surgery, but no impact injury). Two of the groups subjected to the injury were supplemented with 10 or 40 mg/kg/day of O3FA; the third injured group served as an unsupplemented control group. The sham-injured rats likewise received no O3FA supplementation. Serum fatty acid levels were determined from the isolated plasma phospholipids prior to the injury and at the end of the 30 days of supplementation. After the animals had been killed, immunohistochemical analysis of brainstem white matter tracts was performed to assess the presence of β-amyloid precursor protein (APP), a marker of axonal injury. Immunohistochemical analyses of axonal injury mechanisms-including analysis for caspase-3, a marker of apoptosis; RMO-14, a marker of neurofilament compaction; and cytochrome c, a marker of mitochondrial injury-were performed. RESULTS Dietary supplementation with a fish oil concentrate rich in EPA and DHA for 30 days resulted in significant increases in O3FA serum levels: 11.6% ± 4.9% over initial levels in the 10 mg/kg/day group and 30.7% ± 3.6% in the 40 mg/kg/day group. Immunohistochemical analysis revealed significantly (p < 0.05) decreased numbers of APP-positive axons in animals receiving O3FA supplementation: 7.7 ± 14.4 axons per mm(2) in the 10 mg/kg/day group and 6.2 ± 11.4 axons per mm(2) in the 40 mg/kg/day group, versus 182.2 ± 44.6 axons per mm(2) in unsupplemented animals. Sham-injured animals had 4.1 ± 1.3 APP-positive axons per mm(2). Similarly, immunohistochemical analysis of caspase-3 expression demonstrated significant (p < 0.05) reduction in animals receiving O3FA supplementation, 18.5 ± 28.3 axons per mm(2) in the 10 mg/kg/day group and 13.8 ± 18.9 axons per mm(2) in the 40 mg/kg/day group, versus 129.3 ± 49.1 axons per mm(2) in unsupplemented animals. CONCLUSIONS Dietary supplementation with a fish oil concentrate rich in the O3FAs EPA and DHA increases serum levels of these same fatty acids in a dose-response effect. Omega-3 fatty acid supplementation significantly reduces the number of APP-positive axons at 30 days postinjury to levels similar to those in uninjured animals. Omega-3 fatty acids are safe, affordable, and readily available worldwide to potentially reduce the burden of traumatic brain injury.

Internal jugular vein compression mitigates traumatic axonal injury in a rat model by reducing the intracranial slosh effect.

BACKGROUND Traumatic brain injury (TBI) remains a devastating condition for which extracranial protection traditionally has been in the form of helmets, which largely fail to protect against intracranial injury. OBJECTIVE To determine whether the pathological outcome after traumatic brain injury can be improved via slosh mitigation by internal jugular vein (IJV) compression. METHODS Two groups of 10 adult male Sprague-Dawley rats were subjected to impact-acceleration traumatic brain injury. One group underwent IJV compression via application of a collar before injury; the second group did not. Intracranial pressure and intraocular pressure were measured before and after IJV compression to assess collar performance. All rats were killed after a 7-day recovery period, and brainstem white matter tracts underwent fluorescent immunohistochemical processing and labeling of β-amyloid precursor protein, a marker of axonal injury. Digital imaging and statistical analyses were used to determine whether IJV compression resulted in a diminished number of injured axons. RESULTS Compression of the IJV resulted in an immediate 30% increase in intraocular and intracranial pressures. Most notably, IJV compression resulted in > 80% reduction in the number of amyloid precursor protein-positive axons as indicated by immunohistochemical analysis. CONCLUSION Using a standard acceleration-deceleration laboratory model of mild traumatic brain injury, we have shown successful prevention of axonal injury after IJV compression as indicated by immunohistochemical staining of amyloid precursor protein. We argue that IJV compression reduces slosh-mediated brain injury by increasing intracranial blood volume, which can be indirectly measured by intracranial and intraocular pressures.

Anabolic Steroids and Head Injury

BACKGROUND The suggestion has been made that neurological changes seen in the syndrome of chronic traumatic encephalopathy may be due to exogenous anabolic steroid use rather than traumatic brain injury. OBJECTIVE To determine whether administration of anabolic steroids alters the pathophysiology of traumatic brain injury. METHODS Sixty adult male Sprague-Dawley rats and a linear acceleration model of traumatic brain injury were used. Experimental groups were (1) preinjury anabolic steroids, (2) preinjury placebo carrier, (3) anabolic steroids without injury, (4) no steroids and no injury, (5) postinjury placebo carrier, and (6) postinjury anabolic steroids. Following a 30-day recovery, rats were euthanized, and brainstem white matter tracts underwent fluorescent immunohistochemical processing and labeling of &bgr;-amyloid precursor protein (APP), a marker of axonal injury. Digital imaging and statistical analyses were used to determine whether anabolic steroid administration resulted in a significant change in the number of injured axons. RESULTS There was no statistically significant difference in number of APP-positive axons by immunohistochemical analysis between respective anabolic steroid and placebo groups. CONCLUSION Using a standard acceleration-deceleration model of mild traumatic brain injury, we have shown successful visualization of traumatically injured axons with antibody staining of APP. Our results indicate no statistically significant effect of anabolic steroids on the number of APP-positive axons. With the use of this model, and within its limitations, we see no adverse effect or causative role of anabolic steroid administration on the brain following mild traumatic brain injury using APP counts as a marker for anatomic injury.

Intracardiac versus transesophageal echocardiography to guide transcatheter closure of interatrial communications: Nationwide trend and comparative analysis

OBJECTIVES This study aimed to assess current temporal trends in utilization of ICE versus TEE guided closure of interatrial communications, and to compare periprocedural complications and resource utilization between the two imaging modalities. BACKGROUND While transesophageal echocardiography (TEE) has historically been used to guide percutaneous structural heart interventions, intracardiac echocardiography (ICE) is being increasingly utilized to guide many of these procedures such as closure of interatrial communications. METHODS Using the Nationwide Inpatient Sample, all patients aged >18 years, who underwent ASD or PFO closure with either ICE or TEE guidance between 2003 and 2014 were included. Comparative analysis of outcomes and resource utilization was performed using a propensity score-matching model. RESULTS ICE guidance for interatrial communication closure increased from 9.7% in 2003 to 50.6% in 2014. In the matched model, the primary endpoint of major adverse cardiovascular events occurred less frequently in the ICE group versus the TEE group (11.1% vs 14.3%, respectively, P = 0.008), mainly driven by less vascular complications in the ICE group (0.5% vs 1.3%, P = 0.045). Length of stay was shorter in the ICE group (3 ± 4 vs 4 ± 4 days, P < 0.0001). Cost was similar in the two groups 18 454 ± 17 035

Whale tail left atrial appendage anatomy: implications for percutaneous closure devices

in the TEE group vs 18 278 ± 15 780

The Feasibility of Transcatheter Edge-to-Edge Repair in the Management of Acute Severe Ischemic Mitral Regurgitation

in the ICE group (P = 0.75). CONCLUSIONS Intracardiac echocardiogram utilization to guide closure of interatrial communications has plateaued after a rapid rise throughout the 2000s. When utilized to guide interatrial communication closure procedure, ICE is as safe as TEE and does not increase cost or prolonged hospitalizations.

The sheer stress of deciding when to replace the aorta in bicuspid valve disease

Percutaneous left atrial appendage (LAA) closure is feasible in the majority of patients. However, certain LAA anatomies may pose substantial technical challenges. We describe two unusual ‘Whale Tail’-like LAAs and novel closure methods with the Watchman (Boston Scientific, Marlborough, MA, USA) and Amulet (Abbott, St Paul, MN, USA) Devices. Patient 1: A 67-year-old male with atrial fibrillation (CHA2DS2-VASc1⁄4 6) was referred for LAA closure due to gastrointestinal bleeding on Warfarin. Transoesophageal echocardiography (TOE) showed a bilobar LAA (Supplementary material online, Video S1). He declined thoracoscopic surgical exclusion. Left atrial appendage angiography revealed a whale tail-like appearance (Panel A). Placement of an oversized Watchman device (24-mm) was unsuccessful in sealing the LAA. A second transseptal puncture was performed, and two 21-mm