CRYAB plays a role in terminating the presence of pro-inflammatory macrophages in the older, injured mouse peripheral nervous system.

Evidence indicates that dysfunction of older Schwann cells and macrophages contributes to poor regeneration of more mature peripheral nervous system (PNS) neurons after damage. Since the underlying molecular factors are largely unknown, we investigated if CRYAB, a small heat shock protein that is expressed by Schwann cells and axons and whose expression declines with age, impacts prominent deficits in the injured, older PNS including down-regulation of cholesterol biosynthesis enzyme genes, Schwann cell dysfunction, and macrophage persistence. Following sciatic nerve transection injury in 3- and 12-month-old wildtype and CRYAB knockout mice, we found by bulk RNA sequencing and RT-PCR, that while gene expression of cholesterol biosynthesis enzymes is markedly dysregulated in the aging, injured PNS, CRYAB is not involved.

Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury.

Background: Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain.

Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis.

The cysteine protease inhibitor Cystatin C (CST3) is highly expressed in the brains of multiple sclerosis (MS) patients and C57BL/6J mice with experimental autoimmune encephalomyelitis (EAE; a model of MS), but its roles in the diseases are unknown. Here, we show that CST3 plays a detrimental function in myelin oligodendrocyte glycoprotein 35-55 (MOG)-induced EAE but only in female animals. Female Cst3 null mice display significantly lower clinical signs of disease compared to wild-type (WT) littermates.

Establishing User Error on the Patient-Reported Component of the American Shoulder and Elbow Surgeons Shoulder Score.

Background: The American Shoulder and Elbow Surgeons (ASES) score is a patient-reported outcome (PRO) questionnaire developed to facilitate communication among international investigators and to allow comparison of outcomes for patients with shoulder disabilities. Although this PRO measure has been deemed easy to read and understand, patients may make mistakes when completing the questionnaire.

Purpose: To evaluate the frequency of potential mistakes made by patients completing the ASES score.

A rare case of septic knee following prolotherapy injections.

Prolotherapy injections are becoming increasingly popular as a non-surgical treatment option for many chronic musculoskeletal conditions. Proposed benefits include reduced pain, reduced joint laxity and increased tendon strength. While a number of studies report that prolotherapy reduces pain and increases function for many conditions, the academic evidence remains extremely weak.

Experimental study on pressure response to graded spinal canal compromise in an burst fracture mode.

Background: Spinal cord compression is a known cause of spinal cord injury. The purpose of this study is to measure pressure response during graded spinal cord compression. This information will be important in evaluating the amount of canal compromise that can be tolerated before risking neurological injury secondary to cord compression.

Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain.

Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain.

Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury.

Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective.

AlphaB-crystallin expression correlates with aging deficits in the peripheral nervous system.

In an effort to identify factors that contribute to age-related deficits in the undamaged and injured peripheral nervous system (PNS), we noted that Brady and colleagues found that mice null for a small heat shock protein called alphaB-crystallin (αBC) developed abnormalities early in life that are reminiscent of aging pathologies. Because of our observation that αBC protein levels markedly reduce as wild-type mice age, we investigated whether the crystallin plays a role in modulating age-related deficits in the uninjured and damaged PNS. We show here that the presence of αBC correlates with maintenance of myelin sheath thickness, reducing macrophage presence, sustaining lipid metabolism, and promoting remyelination following peripheral nerve injury in an age-dependent manner.

AlphaB-crystallin regulates remyelination after peripheral nerve injury.

AlphaB-crystallin (αBC) is a small heat shock protein that is constitutively expressed by peripheral nervous system (PNS) axons and Schwann cells. To determine what role this crystallin plays after peripheral nerve damage, we found that loss of αBC impaired remyelination, which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmyelinating Schwann cells. The heat shock protein also seems to regulate the cross-talk between Schwann cells and axons, because expected changes in neuregulin levels and ErbB2 receptor expression after PNS injury were disrupted in the absence of αBC.

Diurnal influences on electrophysiological oscillations and coupling in the dorsal striatum and cerebellar cortex of the anesthetized rat.

Circadian rhythms modulate behavioral processes over a 24 h period through clock gene expression. What is largely unknown is how these molecular influences shape neural activity in different brain areas. The clock gene Per2 is rhythmically expressed in the striatum and the cerebellum and its expression is linked with daily fluctuations in extracellular dopamine levels and D2 receptor activity.