Central defect type partial ACL injury model on goat knees: the effect of infrapatellar fat pad excision

BACKGROUND: The mid-substance central defect injury has been used to investigate the primary healing capacity of the anterior cruciate ligament (ACL) in a goat model. The sagittal plane stability on this model has not been confirmed, and possible effects of fat pad excision on healing have not been evaluated. We hypothesize that excising the fat pad tissue results in poorer ligament healing as assessed histologically and decreased tensile strength of the healing ligament. We further hypothesize that the creation of a central defect does not affect sagittal plane knee stability. METHODS: A mid-substance central defect was created with a 4-mm arthroscopic punch in the ACLs of right knees of all the subjects through a medial mini-arthrotomy. Goats were assigned to groups based on whether the fat pad was preserved (group 1, n = 5) or excised completely (group 2, n = 5). The left knees served as controls in each goat. Histopathology of the defect area along with measurement of type I collagen in one goat from each group were performed at 10th week postoperatively. The remaining knees were evaluated biomechanically at the 12th week, by measuring anterior tibial translation (ATT) of the knee joints at 90° of flexion and testing tensile properties (ultimate tensile load (UTL), ultimate elongation (UE), stiffness (S), failure mode (FM)) of the femur-ACL-tibia complex. RESULTS AND DISCUSSION: Histopathology analysis revealed that the central defect area was fully filled macroscopically and microscopically. However, myxoid degeneration and fibrosis were observed in group 2 and increased collagen type I content was noted in group 2. There were no significant differences within and between groups in terms of ATT values (p = 0.715 and p = 0.149, respectively). There were no significance between or within groups in terms of ultimate tensile load and ultimate elongation; however, group 2 demonstrated greater stiffness than group 1 that was correlated with the fibrotic changes detected microscopically (p = 0.043). CONCLUSIONS: The central defect type injury model was confirmed to be biomechanically stable in a goat model. Resection of the fat pad was noted to negatively affect defect healing and increase ligament stiffness in the central defect injury model

Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

Background: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings: Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACE

BMP9 Protects Septal Neurons from Axotomy-Evoked Loss of Cholinergic Phenotype

Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP) 9 is a cholinergic differentiating factor during development both in vivo and in vitro.To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT)-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75) and TrkA (NTRK1), and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2) protein.These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells

Biomechanical considerations in the pathogenesis of osteoarthritis of the knee

Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity