Decoupled Epineurial and Axonal Deformation in Mouse Median and Ulnar Nerves

Peripheral nerves span one or more articulating joints, and must accommodate mechanical loads during day-to-day activities. Axons are protected in part by their undulation within the nerve, implied by the Bands of Fontana. In addition, previous studies have identified regions of increased epineurial strain and compliance, particularly near joints. Most of these studies have focused on regional differences in epineurial strain; however, how internal nerve compartments, including the axons, perceive this increased deformation is less understood. Using transgenic mice expressing a fluorescent reporter within their neurons, we tested 1) whether mesoneurial tissue contributes to regional variability in epineurial strain, and 2) whether nerves increase their local axonal undulation in regions of high epineurial strain, as a strategy to protect nerve fibers from strain-induced damage.In our results, we observed a decoupling between regions of high epineurial strain and high axonal tortuosity. Consistent with previous studies, decompression resulted in significant differences in regional strain, confirming strong mesoneurial influences on epineurial strain. However, regional differences in axonal tortuosity were largely unchanged by decompression or excision, signaling that epineurial measurements may not fully represent the response of the inner nerve. Based on our findings and previous literatures, we propose a neuromechanical model that permits axons to unravel along their length due to looser coupling between the peri/endoneurium. This capability may result in enhanced axonal protection to injury than suspected. These findings have implications for our understanding of nerve biomechanics as well as the progression of nerve dysfunction due to injury, disease, or surgery

Changing Medical Paradigm on Inflammatory Eye Disease: Technology and Its Implications for P4 Medicine

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Native paraneurial tissue and paraneurial adhesions alter nerve strain distribution in rat sciatic nerves.

Paraneurial adhesions have been implicated in the pathological progression of entrapment neuropathies. Surgical decompression of adhesions is often performed, with the intent of restoring nerve kinematics. The normal counterpart of adhesions, native paraneurium, is also thought to influence nerve deformation and mobility. However, influences of native or abnormal paraneurial structures on nerve kinematics have not been investigated. We measured regional strains in rat sciatic nerves before and immediately after decompression of native paraneurial tissue, and before and after decompression of abnormal paraneurial adhesions, which formed within 6 weeks of the initial decompression. Strain was significantly higher in the distal-femoral than in the mid-femoral region of the nerve before either decompression. Decompression of native and abnormal paraneurial tissue removed this regional strain difference. Paraneurial tissues appear to play a major role in distributing peripheral nerve strain. Normal nerve strain distributions may be reconstituted following decompression, even in the presence of paraneurial adhesions

Native paraneurial tissue and paraneurial adhesions alter nerve strain distribution in rat sciatic nerves.

Paraneurial adhesions have been implicated in the pathological progression of entrapment neuropathies. Surgical decompression of adhesions is often performed, with the intent of restoring nerve kinematics. The normal counterpart of adhesions, native paraneurium, is also thought to influence nerve deformation and mobility. However, influences of native or abnormal paraneurial structures on nerve kinematics have not been investigated. We measured regional strains in rat sciatic nerves before and immediately after decompression of native paraneurial tissue, and before and after decompression of abnormal paraneurial adhesions, which formed within 6 weeks of the initial decompression. Strain was significantly higher in the distal-femoral than in the mid-femoral region of the nerve before either decompression. Decompression of native and abnormal paraneurial tissue removed this regional strain difference. Paraneurial tissues appear to play a major role in distributing peripheral nerve strain. Normal nerve strain distributions may be reconstituted following decompression, even in the presence of paraneurial adhesions

Decoupled epineurial and axonal deformation in mouse median and ulnar nerves.

INTRODUCTION: Peripheral nerves accommodate mechanical loads during joint movement. Hypothesized protective features include increased nerve compliance near joints and axonal undulation. How axons perceive nerve deformation is poorly understood. We tested whether nerves increase local axonal undulation in regions of high epineurial strain to protect nerve fibers from strain-induced damage. METHODS: Regional epineurial strain was measured near the elbow in median and ulnar nerves of mice expressing axonal fluorescence before and after decompression. Regional axonal tortuosity was quantified under confocal microscopy. RESULTS: Nerves showed higher epineurial strain just distal to the medial epicondyle; these differences were eliminated after decompression. Axonal tortuosity also varied regionally; however, unlike in the epineurium, it was greater in proximal regions. DISCUSSION: In this study we have proposed a neuromechanical model whereby axons can unravel along their entire length due to looser mechanical coupling to the peri/epineurium. Our findings have major implications for understanding nerve biomechanics and dysfunction. Muscle Nerve 59:619-619, 2019

Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology

Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction method would impact therapeutic decision-making in corneal transplantation. Valuable insights into the clinically observed heterogeneity of host responses to corneal grafts have emerged from multidisciplinary approaches, including genomics analyses, mechanical studies, immunobiology, and theoretical modeling. Here, we review the emerging concepts, tools, and new biomarkers that may allow for the prediction of graft survival

Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology.

Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction method would impact therapeutic decision-making in corneal transplantation. Valuable insights into the clinically observed heterogeneity of host responses to corneal grafts have emerged from multidisciplinary approaches, including genomics analyses, mechanical studies, immunobiology, and theoretical modeling. Here, we review the emerging concepts, tools, and new biomarkers that may allow for the prediction of graft survival

Effect of Resident Involvement in Ophthalmic Surgery on Patient Outcomes: A Systematic Review and Meta-analysis.

PURPOSE: To determine the effect of resident- vs attending-led surgeries on patient outcomes in ophthalmic surgery. DESIGN: Systematic review and meta-analysis. METHODS: Two independent authors searched PubMed, EMBASE, and Cochrane Library from inception to March 2022. Categorical data from studies were pooled to report odds ratio (OR) and 95% CIs. Continuous data were analyzed to yield standardized mean difference (SMD) and 95% CIs. Propensity-matched studies were analyzed separately. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Twenty-four studies were included in this meta-analysis. Seventeen of the 20 outcomes had no significant differences between the 2 cohorts. Notably, many critical cataract surgery-related outcomes showed no significant differences, including posterior capsular tear, lens fragment retainment, and retinal detachment. Among propensity-scored studies, the resident-led surgeries had longer operative duration (SMD 0.81, 95% CI 0.29, 1.33; 3 studies [260 patients], I CONCLUSIONS: Resident-led surgeries appear overall safe, effective, and comparable to attending-led surgeries with respect to commonly encountered perioperative complications. Specific differences in outcomes exhibit significant heterogeneity and small sample sizes, and may be of unclear or equivocal clinical significance