Cerebral microbleeds in people are small foci of hemosiderin-containing macrophages in normal brain parenchyma. They are the remnant of previous hemorrhage and occur with greater frequency in older individuals. Our purpose was to describe the magnetic resonance (MR) appearance of cerebral microbleeds in four dogs. These lesions appeared as round, hypointense foci measuring ≤4 mm on T2*-gradient-recalled echo images. They were less conspicuous or absent on T2-weighting, being iso- or hypointense, and uniformly invisible on T1-weighted images. No contrast enhancement was seen in any of the cerebral microbleeds. Necropsy-derived histopathologic analysis of one brain confirmed these lesions to be chronic cerebrocortical infarcts containing hemosiderin. The MR changes seen in dogs were analogous to what has been described in people and will be helpful in distinguishing cerebral microbleeds from other brain lesions.
T hirteen percent of global mortality has been associated with arterial hypertension. Approximately 34% of the total adult population worldwide is hypertensive, and 13% of this segment of the population is further categorized as having resistant hypertension (RHTN).1 Criteria for the diagnosis of RHTN are the following: any patient requiring ≥3 antihypertensive drugs, including a diuretic, and still maintaining a blood pressure (BP) >140/90 mm Hg.2 RHTN has been previously described as a multifactorial phenomenon involving multiple biological mechanisms; however, the hyperactivity of the sympathetic nervous system plays a paramount role in the onset, maintenance, and progression of RHTN. 3 The renal sympathetic nervous system, composed of afferent and efferent nerves, courses immediately adjacent to the wall of the renal artery. 4 The afferent renal sensory nerves, with neuronal cell bodies located in the ipsilateral dorsal root ganglia, modulate the central sympathetic outflow by providing sensory information from mechanoreceptors and chemoreceptors in the renal tissue. Renal injuries (ie, hypoxia) increase afferent sensory signals, resulting in an increase in efferent sympathetic nerve activity, peripheral arterial vasoconstriction, and subsequent increase in arterial BP. The efferent renal sympathetic nerves transmit signals from the central sympathetic nervous system to the kidneys (ie, renal vasculature, tubules, and juxtaglomerular apparatus). Efferent renal sympathetic activity is moderated by an inhibitory renorenal reflex and central sympathetic nervous system outflow. Elevated efferent renal sympathetic activity increases sodium reabsorption and renin release and causes renal arterial vasoconstriction, leading to hypertension. Catheter-based ablation of afferent and efferent sympathetic nerves surrounding the renal arteries has been proposed Background-Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN. Methods and Results-Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thick...
Bioabsorbable implants can be advantageous for certain surgical tissue bioengineering applications and implant-assisted tissue repair. They offer the obvious benefits of nonpermanence and eventual restoration of the native tissue's biomechanical and immunological properties, while providing a structural scaffold for healing and a route for additional therapies (i.e., drug elution). They present unique developmental, imaging, and histopathological challenges in the conduct of preclinical animal studies and in interpretation of pathology data. The bioabsorption process is typically associated with a gradual decline (over months to years) in structural strength and integrity and may also be associated with cellular responses such as phagocytosis that may confound interpretation of efficacy and safety end points. Additionally, as these implants bioabsorb, they become increasingly difficult to isolate histologically and thus imaging modalities such as microCT become very valuable to determine the original location of the implants and to assess the remodeling response in tandem with histopathology. In this article, we will review different types of bioabsorbable implants and commonly used bioabsorbable materials; additionally, we will address some of the most common challenges and pitfalls confronting histologists and pathologists in collecting, handling, imaging, preparing tissues through histology, evaluating, and interpreting study data associated with bioabsorbable implants.
Category: Basic Sciences/Biologics; Other Introduction/Purpose: The integration of an implant into surrounding tissue as remodeling occurs is a characteristic associated with bone grafts or bone fillers, some of which are osteoconductive or osteostimulative. Many bioabsorbable polymer implants lack quiescent degradation and are associated with adverse inflammation. Recently, new bio-integrative bone fixation implants comprised of continuous mineral fibers and polymer were introduced. The implant’s high mineral content is intended to encourage an increased bio-integrative response, while the continuous fiber structure provides mechanical bone fixation strength. The study objectives were to evaluate the implant’s long-term bio-integration and ability to maintain fixation in a load bearing in- vivo model. Methods: Twenty-four rabbits were studied over 104-week period to evaluate the bio-integration of fiber-reinforced bone fixation pins. The continuous reinforcing mineral fibers made up approximately 50% of the implant, comprised of elements found in native bone, including calcium, silica, and magnesium. The other 50% was comprised of poly (L-lactide-co-D, L lactide) (PLDLA) at a 70:30, L:DL ratio. Pins were implanted bilaterally, with three fiber-reinforced pins (test) implanted into the mid-shaft of one femur and three PLDLA polymer pins (control) into the mid-shaft of the other femur. Implantation sites were scored histologically at multiple timepoints to assess bio-integration by means of implant degradation profile, surrounding bone quality and tissue ingrowth. A separate group of twelve rabbits was studied clinically, radiographically and histologically over 12 weeks to evaluate the fiber-reinforced implant performance, compared to a stainless-steel implanted group, in a lateral femur condyle osteotomy model under full load bearing conditions. Results: At 104 weeks, implant material fully eliminated in 11 out of 12 fiber-reinforced implants and in 6 out of 12 PLDLA implants. The fiber-reinforced group showed increased propensity for bio-integration throughout the course of the study, demonstrating a gradual degradation profile and much higher score of tissue ingrowth. Amount of polymer decreased from a score of 4.0 at 4 weeks to score 1.7 at week 26, score 1.0 at week 78 and 0.1 at 104 weeks. The polymer control underwent abrupt late stage degradation, with amount of polymer dropping from a score of 4.0 to 0.7 from 78 to 104 weeks. In the load bearing osteotomy model, the fiber-reinforced implants performed comparable to stainless-steel, demonstrating tighter bone-to- implant interface with no intervening fibrotic tissue. Conclusion: This study represents the first long term in-vivo evaluation of mineral fiber-reinforced implants demonstrating both bio-integration and orthopedic fixation. Quiescent bio-integration is a significant challenge for degradable orthopedic fixation implants. The implants must be mechanically strong for stable fixation while able to gradually integrate with surrounding bone without adverse effects. Continuous fiber reinforced implants proved the unique potential to meet this challenge with a fiber structure that provides fixation strength and is comprised entirely of minerals found in native bone. An increased level of mesenchymal tissue ingrowth, combined with the absence of local or systemic adverse response, demonstrates excellent bio- integration.
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